CN1193026C - Z-pyrazoline-5-ones - Google Patents

Abstract

The compounds of structural formula (I) and their physiologically acceptable salts are inhibitors of serine/threonine and tyrosine kinase activity. Several tyrosine kinases whose activity is inhibited by these compounds are involved in angiogenesis. Therefore, these compounds can improve disease conditions in which angiogenesis or endothelial cell proliferation is a factor. These compounds may be used to treat cancer and proliferative diseases.

Description

2-pyrazolin-5-one

technical field

This application claims the benefit of US Provisional Application 60/146,563, filed July 30, 1999, which is incorporated herein by reference in its entirety.

The present invention relates to certain 2-pyrazolin-5-ones, which are inhibitors of protein kinases, especially tyrosine kinases and serine/threonine kinases, some of which are novel compounds, and to compounds containing these pyrazoles Pharmaceutical compositions of pyrazolones and methods for the preparation of these pyrazolones.

Background technique

At least 400 protein kinases have been identified. These enzymes catalyze the phosphorylation of target protein substrates. Phosphorylation is usually the transfer of a phosphate group from ATP to a protein substrate. The specific structure of the target substrate to which the phosphate is transferred is a tyrosine, serine or threonine residue. Since these amino acid residues are target substrates for phosphoryl transfer, these protein kinases are often referred to as tyrosine kinases or serine/threonine kinases.

Phosphorylation and counterbalancing phosphatase reactions on tyrosine, serine, or threonine residues are involved in a myriad of cellular processes that are based on responses to different intracellular signals (often initiated by cellular receptors mediated), involved in the regulation of cellular functions and the activation or inactivation of cellular processes. Cascades of protein kinases are frequently involved in the transduction of intracellular signals and are essential for the realization of these cellular processes. Because of their ubiquity in these processes, protein kinases can be found as integral parts of the plasma membrane or as cytoplasmic enzymes, or localized in the nucleus, often as components of enzyme complexes. In many cases, these protein kinases are fundamental elements of enzyme and structural protein complexes that determine if or when cellular processes occur in cells.

protein tyrosine kinase. Protein tyrosine kinases (PTKs) are enzymes that catalyze the phosphorylation of specific tyrosine residues in cellular proteins. Post-translational modifications of these substrate proteins, often the enzymes themselves, function as molecular switches controlling cell proliferation, activation or differentiation (for review, see Schlessinger and Ulrich, 1992, Neuron 9:383-391). Lost or excessive is observed in many diseases, including benign and malignant proliferative diseases and diseases caused by inappropriate activation of the immune system (such as autoimmune diseases), allograft rejection and graft-versus-host rejection diseases PTKs activity. Furthermore, endothelial cell-specific receptor PTKs such as KDR and Tie-2 mediate the angiogenic process and are thus implicated in supporting cancer and other diseases associated with inappropriate vascularization (e.g. diabetic retinopathy, Choroidal neovascularization, psoriasis, arthritis, retinopathy of prematurity, infantile hemangioma).

Tyrosine kinases can be receptor-type (having extracellular, transmembrane and intracellular domains) or non-receptor-type (entirely intracellular).

Receptor tyrosine kinases (RTKs). RTKs comprise a large family of transmembrane receptors that possess a variety of biological activities. Currently, at least 19 different RTK subfamilies have been identified. The receptor tyrosine kinase (RTK) family includes receptors that are decisive for the growth and differentiation of various cell types (Yarden and Ullrich, Ann. Rev. Biochem. 57:433-478, 1988; Ullrich and Schlessinger, Cell 61 : 243-254, 1990). Upon ligand binding, the intrinsic functions of RTKs are activated, leading to phosphorylation of receptors and multiple cellular substrates, which subsequently lead to a variety of cellular responses (Ullrich & Schlessinger, 1990, Cell 61:203-212). Thus, receptor tyrosine kinase-mediated signaling begins with extracellular interactions with specific growth factors (ligands), often followed by dimerization of the receptor, stimulating the activity of intrinsic protein tyrosine kinases and receptor phosphate transfer. This creates binding sites for intracellular signaling molecules and leads to the formation of complexes with a range of cytoplasmic signaling molecules to facilitate appropriate cellular responses. (eg cell division, differentiation, metabolism, changes in the extracellular niche), see Schlessinger and Ullrich, 1992, Neuron 9:1-20.

Proteins with SH2 (src homology-2) or phosphotyrosine-binding (PTB) domains bind activated tyrosine kinase receptors and their substrates with high affinity to propagate the signal to the cell. Both of the above two regions recognize phosphotyrosine. (Fantl et al., 1992, Cell 69:413-423; Songyang et al., 1994, Mol.Cell.Biol.14:2777-2785; Songyang et al., 1993, Cell 72:767 -778; and Koch et al., 1991, Science 252:668-678; Shoelson, Curr.Opin.Chem.Biol. (1997), 1(2), 227-234; Cowburn, Curr.Opin.Struct.Biol.( 1997), 7(6), 835-838). Several intracellular substrate proteins associated with receptor tyrosine kinases (RTKs) have been identified. They can be divided into two main groups: (1) substrates with catalytic domains; and (2) substrates lacking catalytic domains but acting as adapters and associated with catalytically active molecules (Songyang et al., 1993, Cell 72:767-778). The specificity with which the receptor or protein of its substrate interacts with the SH2 or PTB domain is determined by the amino acid residues immediately surrounding the phosphorylated tyrosine residue. For example, differences in binding affinities between the SH2 domain on a particular receptor and the amino acid sequences surrounding the phosphotyrosine residues are related to differences in the phosphorylation properties of their substrates (Songyang et al., 1993, Cell 72:767- 778). These observations imply that the function of each receptor tyrosine kinase is determined not only by its expression pattern and ligand availability, but also by the arrangement of downstream signaling pathways activated by a particular receptor, the timing and duration of those stimuli . Phosphorylation thus provides an important regulatory step that determines the selectivity of signaling pathways complemented by specific growth factor receptors as well as differentiation factor receptors.

Several receptor tyrosine kinases such as FGFR-1, PDGFR, and c-Met, and the growth factors that bind to them, have been suggested to play a role in angiogenesis, although some may promote angiogenesis indirectly (Mustonen and Alitalo, J Cell Biol. 129:895-898, 1995). A receptor tyrosine kinase known as "fetal liver kinase 1" (FLK-1) is a member of a subclass of type III RTKs. Alternatively for human FLK-1 it is designated "Kinase Inserted Region Receptor" (KDR) (Terman et al., Oncogene 6:1677-83, 1991). Another designation for FLK-1/KDR is "vascular endothelial growth factor receptor 2" (VEGFR-2) because of its high affinity binding to VEGF. Murine FLK-1/VEGFR-2 is also known as NYK (Oelrichs et al., Oncogene 8(1):11-15, 1993). DNA-encoded mouse, rat, and human FLK-1 have been isolated, and nucleotide and encoded amino acid sequences have been reported (Matthews et al., Proc.Natl.Acad.Sci.USA, 88:9026-30, 1991 ; Terman et al., 1991, supra; Terman et al., Biochem. Biophys. Res. Comm. 187:1579-86, 1992; Sarzani et al., supra; and Millauer et al., Cell 72:835-846, 1993). Many studies, such as the above report by Millauer et al., have suggested that VEGF and FLK-1/KDR/VEGFR-2 are ligand-receptor pairs that play an important role in the proliferation of vascular endothelial cells and in angiogenesis and sprouting, Vascular endothelial cell proliferation and vessel formation and sprouting are termed angiogenesis and angiogenesis, respectively.

Another type III RTK named "fin-like tyrosine kinase-1" (Flt1) is related to FLK-1/KDR (DeVries et al., Science 255; 989-991, 1992; Shibuya et al., Oncogene 5:519 -524, 1990). Another name for Flt-1 is "vascular endothelial growth factor receptor 1" (VEGFR-1). To date, many FLK-1/KDR/VEGFR-2 and Flt-1/VEGFR-1 subfamilies expressed mainly on endothelial cells have been discovered. Members of these subfamilies are specifically stimulated by a number of vascular endothelial cell growth factor (VEGF) ligands (Klagsburn and D'Amore, Cytokine & Growth Factor Reviews 7:259-270, 1996). Vascular endothelial growth factor (VEGF) binds Flt-1 with high affinity compared to FLK-1/KDR and is mitogenic to vascular endothelial cells (Terman et al., 1992, supra; Mustonen et al., supra; DeVries et al. et al., supra). Flt-1 is believed to be essential for endothelial tissue in vascular development. Flt-1 expression is associated with early vascular development in mouse embryos and with neovascularization during wound healing (Mustonen and Alitalo, supra). Expression of Flt-1 in mature organs such as the glomerulus suggests additional functions for this receptor that are not related to cell growth (Mustonen and Alitalo, supra).

As noted above, recent evidence suggests that VEGF plays an important role in stimulating normal and pathological angiogenesis (Jakeman et al., Endocrinology 133:848-859, 1993; Kolch et al., Breast Cancer Research and Treatment 36:139-155, 1995; Ferrara et al. et al., Endocrine Reviews 18(1); 4-25, 1997; Ferrara et al., Regulation of Angiogenesis (ed. L.D. Goldberg and E.M. Rosen), 209-232, 1997). In addition, VEGF is related to the control and enhancement of blood vessel permeability (Connolly, et al., J.Biol.Chem.264:20017-20024, 1989; Brown et al., Regulation of Angiogenesis (ed.L.D.Goldberg and E.M.Rosen), 233- 269, 1997).

Different forms of VEGF resulting from alternative mRNA splicing have been reported, including the four species described by Ferrara et al. (J. Cell. Biochem. 47:211-218, 1991). Ferrara et al. (supra) have identified VEGF associated with secretory and primary cells, and the protein is known to exist as a disulfide-linked dimer.

Several related VEGF homologs have recently been identified. However, its role in normal physiological and disease processes has not been elucidated. In addition, many members of VEGF are frequently co-expressed with VEGF in many tissues and are often capable of forming heterodimers with VEGF. This property probably alters the specificity of the receptor and the biological role of the heterodimer, and further complicates the elucidation of its specific function as described below (Korpelainen and Alitalo, Curr. Opin. Cell Biol., 159-164, 1998, which reference is incorporated herein by reference).

Placental growth factor (P1GF) has an amino acid sequence showing significant homology to the VEGF sequence (Park et al., J. Biol. Chem. 269: 25646-54, 1994; Maglione et al. Oncogene 8: 925-31, 1993) . Like VEGF, a different species of P1GF results from the splicing of another mRNA, and the protein exists as a dimer (Park et al., supra). P1GF-1 and P1GF-2 bind Flt-1 with high affinity, and P1GF-2 also binds eagerly to neuropilin-1 (Migdal et al., J. Biol. Chem. 273(35):22272-22278), but Does not bind FLK-1/KDR (Park et al., supra). Potential effects of P1GF on vascular permeability and mitogenic effects of VEGF on endothelial cells have been reported in the presence of low concentrations of VEGF (purportedly due to heterodimer formation) (Park et al., supra arts).

VEGF-B is produced in two isoforms (167 and 185 residues), which also bind Flt-1/VEGFR-1. They may play a role in regulating extracellular matrix degradation, cell adhesion, and migration by modulating the expression and activity of urokinase-type plasminogen activator and plasminogen activator inhibitor 1 (Pepper et al., Proc. Natl Acad. Sci. U.S.A. (1998), 95(20): 11709-11714).

VEGF-C was originally cloned as a ligand for VEGFR-3/Flt-4, which are mainly expressed by lymphatic endothelial cells. In its fully active form, VEGF-C can also combine with KDR/VEGFR-2, and stimulate proliferation and migration of endothelial cells in vitro and angiogenesis in in vivo models (Lymboussaki et al., Am.J.Pathol.(1998 ), 153(2):395-403; Witzenbichler et al., Am. J. Pathol. (1998), 153(2), 381-394). The transgenic overexpression of TheVEGF-C only caused the proliferation and enlargement of lymphatic vessels, but had no effect on blood vessels. Unlike VEGF, the expression of VEGF-C is not caused by hypoxia (Ristimaki et al., J. Biol. Chem. (1998), 273(14), 8413-8418).

Recently discovered VEGF-D is structurally very similar to VEGF-C. VEGF-D has been reported to bind to and activate at least two VEGFRs, VEGFR-3/Flt-4 and KDR/VEGFR-2. It was originally cloned as a c-fos-inducing mitogen for fibroblasts and is most prominently expressed in mesenchymal cells of the lung and skin (Achen et al., Proc. Natl. Acad. Sci. U.S.A. (1998) , 95(2), 548-553, which is incorporated herein by reference).

Like VEGF, VEGF-C and VEGF-D have been claimed to cause increased vascular permeability in the Miles assay when injected into skin tissue (PCT/US97/14696; W098/07832, Witzenbichler et al., supra). The physiological role and importance of these ligands in the regulation of vascular hyperpermeability and endothelial responses in the tissues in which they are expressed is uncertain.

A virally encoded, novel vascular endothelial growth factor, VEGF-E (NZ-7VEGF), has recently been reported that preferentially utilizes the KDR/Flk-1 receptor and possesses potent mitotic activity rather than a heparin-binding domain (Meyer et al., EMBO J. (1999), 18(2), 363-374; Ogawa et al., J. Biol. Chem. (1998), 273(47), 31273-31282.). The VEGF-E sequence has approximately 25% homology to mammalian VEGF and is encoded by the parapoxvirus Orf virus (OV). The parapoxvirus affects sheep and goats, and occasionally humans, causing lesions with angiogenesis. VEGF-E is an approximately 20 kDa dimer that has neither a basic region nor an affinity for heparin, but has a characteristic cystine knot motif present in all mammalian VEGF, and was unexpectedly found to have the same VEGF-A heparin binds VEGF165 isoforms with similar potency and biological activity, i.e. both factors stimulate tissue factor (TF) release, proliferation, chemotaxis and sprouting of vascular endothelial cells cultured in vitro and angiogenesis in vivo. Like VEGF165, it has been found that VEGF-E binds with high affinity to VEGF receptor-2 (KDR), leading to autophosphorylation of the receptor and a diphasic increase in free intracellular Ca2+ concentration, while in contrast to VEGF165, VEGF-E Does not bind to VEGF receptor-1 (Flt-1).

Based on the discovery of other VEGF and VEGFRs homologues and the precedent of ligand and receptor heterodimerization, the effect of this VEGF homologue may include the formation of heterodimers of VEGF ligands, and/or heterodimers of receptors. Polymerization or binding to as yet undiscovered VEGFR (Witzenbichler et al., supra). Likewise, recent reports suggest that neuropilin-1 (Migdal et al., supra) or VEGFR-3/Flt-4 (Witzenbichler et al., supra) or receptors other than KDR/VEGFR-2 may be involved in causing vascular permeability. Regarding (Stacker, S.A., Vitali, A., Domagala, T., Nice, E. and Wilks, A.F., "Angiogenesis and Cancer" Conference, Amer. Assoc. Cancer Res., Jan. 1998, Orlando, FL; Williams, Diabetelogia 40: S118-120 (1997)). To date, direct evidence that KDR has an important role in VEGF-mediated vascular hyperpermeability has not been published.

Non-receptor tyrosine kinases. Non-receptor tyrosine kinases represent a collection of cellular enzymes that lack extracellular and transmembrane sequences. Currently, more than 24 individual non-receptor tyrosine kinases have been identified, including 11 subfamilies (Src, Frk, Btk, Csk, Abl, Zap70, Fes/Fps, Fak, Jak, Ack, and LIMK). The Src subfamily of non-receptor tyrosine kinases currently consists of the most abundant PTKs and includes Src, Yes, Fyn, Lyn, Lck, Blk, Hck, Fgr, and Yrk. Enzymes of the Src subfamily have been linked to neoplasia and immune responses. A more detailed discussion of non-receptor tyrosine kinases is provided in Bolen, 1993, Oncogene 8:2025-2031, which is incorporated herein by reference.

A number of tyrosine kinases, whether RTKs or non-receptor tyrosine kinases, have been found to be involved in cell signaling pathways involved in many pathogenic conditions including cancer, psoriasis and other hyperproliferative diseases or hyperimmune responses.

Development of compounds that regulate PTKs. Given the importance of putative PTKs for the control, regulation and regulation of cell proliferation, diseases and disorders associated with abnormal cell proliferation, various approaches have been employed to successfully identify receptor and non-receptor tyrosine kinase "inhibitors" , the approach involves the use of mutant ligands (U.S.A. 4,966,849), soluble receptors and antibodies (WO94/10202; Kendall & Thomas, 1994, Proc. Natl. Acad. Sci 90: 10705-09; Kim et al., 1993, Nature 362:841-844), RNA ligand (Jellinek, etc., Biochemistry 33:10450-56; Takano, etc., 1993, Mol.Bio.Cell 4:358A; Kinsella, etc. 1992, Exp.Cell Res.199:56 -62; Wright, et al., 1992, J.Cellular Phys.152:448-57) and tyrosine kinase inhibitors (WO 94/03427; WO 92/21660; WO 91/15495; WO 94/14808; U.S.P. 5,330,992; Mariani, et al., 1994, Proc. Am. Assoc. Cancer Res. 35:2268).

Recently, small molecules have been successfully identified as tyrosine kinase inhibitors. For example, bis monocyclic, bicyclic or heterocyclic aryl compounds (PCT WO 92/20642) and vinylidene azaindole derivatives (PCT WO 94/14808) are generally described as tyrosine kinase inhibitors. Also described styryl compounds (U.S.P. 5,217,999), styryl-substituted pyridyl compounds (U.S.P. 5,302,606), certain quinazoline derivatives (EP application 0 566 266 A1; Expert Opin.Ther.Pat. (1998) , 8(4):475-478), selenoindoles and selenides (PCT WO94/03427), tricyclic polyols (PCT WO 92/21660) and benzylphosphonic acid compounds (PCT WO 91/15495) Used as a tyrosine kinase inhibitor compound for the treatment of cancer. Anilinocinnoline (PCT WO97/34876) and quinazoline derivative compounds (PCT WO97/22596; PCT WO97/42187) have been described as inhibitors of angiogenesis and vascular permeability.

In addition, small molecules have been successfully identified as inhibitors of serine/threonine kinases. For example, bis(indolylmaleimide) compounds have been described to inhibit specific PKC serine/threonine kinase isoforms whose signaling functions are linked to altered vascular permeability in VEGF-related diseases. Transsexual (PCT WO97/40830; PCTWO97/40831).

Plk-1 kinase inhibitor

Plk-1 is a serine/threonine kinase that is an important regulator of cell cycle progression. It plays a decisive role in the assembly and power function of the mitotic spindle apparatus. Plk-1 and related kinases have also been shown to be closely associated with the activation and inactivation of other cell cycle regulators such as cyclin-dependent kinases. High levels of Plk-1 expression are associated with cell proliferation activity. It is frequently seen in malignancies of various origins.

Plk-1 inhibitors are expected to block cancer cell proliferation by interrupting processes associated with the mitotic spindle and inappropriately activated cyclin-dependent kinases.

Cdc2/cyclin B kinase inhibitor (Cdc2 also known as cdkl)

Cdc2/cyclin B is another serine/threonine kinase that belongs to the cyclin-dependent kinases (cdks). These enzymes are involved in the decisive transitions between the progressive phases of the cell cycle. Uncontrolled cell proliferation is believed to be a hallmark of cancer and depends on elevated cdk activity in these cells. Inhibition of elevated cdk activity in cancer cells by cdc2/cyclin B kinase inhibitors inhibits proliferation and restores normal control of cell cycle progression.

There is therefore a need to identify potent small compounds that specifically inhibit signaling and Cell Proliferation. In particular, it would be beneficial to identify methods and compounds that specifically inhibit the function of tyrosine kinases that are critical for the angiogenic process or the formation of vascular hyperpermeability leading to edema, ascites, leaks, exudates and large Molecular extravasation and matrix deposition and associated diseases are required.

Contents of the invention

The present invention relates to compounds of the following formula and physiologically acceptable salts thereof

wherein R is substituted or unsubstituted aliphatic, aromatic, heterocyclic or aralkyl, and ^R is hydrogen, lower alkyl or aryl. R ¹ is hydrogen or -AZ, where A is -(CH ₂ ) _n -, -(CH ₂ ) _n NH-, -(CH ₂ ) _n O-, -(CH ₂ ) _n S-, -(CH ₂ ) _n S(O)- or -(CH ₂ ) _n S(O) ₂ -; and Z is H, lower alkyl, aralkyl, trihalomethyl, R ³ CO-, trihalomethyl Carbonyl, R ³ OC(O)-, -NR ⁴ R ⁵ , -C(O)NR ⁴ R ⁵ , R ³ O- or a ring system selected from the following group: C ₃ -C ₆ cycloalkane, benzene, Pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine, thiophene, imidazole, furan, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole, benzothiazole, tetrahydrofuran, Triazines and applicable N-oxides, these ring systems can optionally be replaced by one or more halogen, lower alkyl, R ³ O-, HO-, HOC(O)-, R ³ OC(O) -, trihalomethyl, nitro, aryl, -CN, -C(O)NR ⁴ R ⁵ or -NR ⁴ R ⁵ substituted. Each occurrence of ^R3 is independently selected from substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl radical, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl. Each occurrence of ^R4 and ^R5 independently of each other is hydrogen or is selected from substituted or unsubstituted: lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl, heterocyclyl, aralkyl , (C ₃ -C ₆ ) cycloalkyl-alkyl and heterocyclyl-alkyl; R ⁴ and R ⁵ can optionally be combined with the nitrogen connected to it to represent morpholino, pyrrolidino ( pyrrolidino), piperidino, imidazol-1-yl, piperazino (piperazino), thiomorpholino, azepino (azepino) or perhydrogenated-1,4-diazepane ( diazepin)-1-yl, wherein each group is optionally substituted by one or more groups selected from the group consisting of lower alkyl, hydroxyl, lower alkoxy lower alkyl, aromatic group, ( C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl; the numerical subscript n is an integer from 0-3.

Suitable substituents for R include halogen, lower alkyl, R ³ O-, hydroxyl, HOC(O)-, R ³ OC(O)-, R ³ OC(O)R ⁶ , R ³ OR ⁶ -, Trihalomethyl, Trihalomethylcarbonyl, Nitro, -C(O)NR ⁴ R ⁵ , -NR ⁴ R ⁵ , R ³ CO-, -(CH ₂ ) _n -R ⁷ , - C(O)(CH ₂ ) _n -R ⁷ , -C(O)-(CH ₂ ) _n -C(O)-R ⁷ , -O(CH ₂ ) _n R ⁷ , -C(O)NR ⁴ (CH ₂ ) _n R ⁷ , C(O)O(CH ₂ ) _n R ⁷ , -OC(O)(CH ₂ ) _n R ⁷ , -NR ⁴ C(O)(CH ₂ ) _n R ⁷ , - R ⁶ NR ⁴ R ⁵ , -R ⁶ N(R ⁴ )-R ⁶ -R ⁷ , -R ⁶ N[R ⁶ -R ⁷ ] ₂ , -R ⁶ C(O)NR ⁴ (CH ₂ ) _n R ⁷ , -R ⁶ C(O)O(CH ₂ ) _n R ⁷ , -R ⁶ OC(O)(CH ₂ ) _n R ⁷ , R ⁶ NR ⁴ C(O)(CH ₂ ) _n R ⁷ , - R ⁶ CH[C(O)OR ⁴ ][NR ⁵ C(O)R ⁴ ] or substituted aryl or aralkyl, wherein the substituents are selected from halogen, trihalomethyl, hydroxyl, -NR ⁴ R ^5. Nitro, -CONR ⁴ R ⁵ , lower alkyl, R ³ O-, C(O)OR ⁴ or -OC(O)R ³ . R ⁶ is lower alkyl or aryl. R ⁷ is alkoxy, haloalkyl, lower alkylpiperazine, hydroxyl, R ³ O-, R ³ C(O)- or -NR ⁴ R ⁵ .

Suitable substituents for R ³ , R ⁴ and R ⁵ include one or more groups selected from the group consisting of halogen, lower alkyl, hydroxyl, lower alkoxy, carboxyl, lower alkyl ester, trihalogen Substituted methyl is preferably trifluoromethyl, nitro, phenyl, phenyl-lower alkyl, (C ₃ -C ₆ )cycloalkyl, (C ₃ -C ₆ )cycloalkyl-alkyl, CN, amino, Alkylamino, dialkylamino, -C(O)NH2, -C( _O )NH(alkyl) and -C(O)N(alkyl) ₂ .

Aliphatic groups include straight or branched C ₁ -C ₁₈ hydrocarbons or cyclic C ₃ -C ₁₈ hydrocarbons which are fully saturated or contain one or more units of unsaturation. Lower alkyl is fully saturated straight or branched C ₁ -C ₆ hydrocarbon or C ₃ -C ₆ cyclic hydrocarbon.

The term aromatic as used herein includes carbocyclic systems such as benzyl and cinnamylidene as well as fused polycyclic aromatic ring systems such as naphthyl. In addition, aromatic groups include heteroaryl ring systems (such as pyridine, thiophene, furan, pyrrole, imidazole, oxazole, thiazole, pyrazole, triazole, pyrimidine, and pyrazine) and heteroaryl ring systems in which the carbocyclic aromatic ring, carbocyclic non-aromatic ring or heteroaromatic ring with one or more other heteroaromatic rings (such as benzimidazole, benzothiazole, indole, tetrahydroindole, azaindole, indazole, isoxazole , isothiazole, imidazole and quinoline) fused. The term aryl as used herein refers to an aromatic group having 5 or 6 atoms. Aralkyl is an aromatic substituent attached to a compound through an aliphatic group having 1-6 carbon atoms. The term heterocyclyl as used herein refers to mono-, bi- or tri-cyclic heterocyclyl groups which are not aromatic or which have a degree of unsaturation which does not constitute an aromatic group.

Tautomers, stereoisomers, enantiomers and mixtures of these compounds are included in the present invention. Pharmaceutically acceptable addition salts of these compounds are also included in the present invention.

Detailed ways

In one embodiment R is ^hydrogen and R is preferably substituted indole or substituted or unsubstituted imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, pyrrole , pyrazole, 4,5,6,7-tetrahydroindole, benzindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene or piperazine.

In a preferred embodiment, ^R is hydrogen, n is 0, and Z is cyclopropyl, 3-pyridyl or pyrazinyl. In another preferred embodiment, ^R2 is hydrogen, A is -O-, n is 0, and Z is ethyl, propyl or isopropyl. In yet another preferred embodiment, R ² is hydrogen, A is CH ₂ , n is 2, and Z is optionally halogen, trihalomethyl, hydroxyl, -NR ⁴ R ⁵ , nitro, - C(O)NR ⁴ R ⁵ , lower alkyl, R ³ O-, -C(O)OR ⁴ or -OC(O)R ³ substituted benzene.

In a preferred embodiment, the present invention relates to compounds represented by the formula: and physiologically acceptable salts thereof:

in:

R is selected from substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzene Indole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole;

R ¹ is hydrogen or -AZ;

A is -(CH ₂ ) _n -, -(CH ₂ ) _n NH-, -(CH ₂ ) _n O-, -(CH ₂ ) _n S-, -(CH ₂ ) _n S(O)-, or - (CH ₂ ) _n S(O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC(O)-, -NR ⁴ R ⁵ , -C(O)NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring system selected from the following group: C ₃ -C ₆ cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole and their N-oxides, wherein the ring system can optionally be Substituted by one or more groups selected from the group consisting of halogen, lower alkyl, R ³ O-, HO-, HOC(O)-, R ³ OC(O)-, trihalomethyl, nitro , Aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl, heterocyclyl-alkyl, -CN, - C(O)NR ⁴ R ⁵ or -NR ⁴ R ⁵ ;

Each occurrence of R ³ is independently selected from substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aryl Alkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl;

Each occurrence of ^R4 and ^R5 independently of each other is hydrogen or is selected from substituted or unsubstituted: lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl, heterocyclyl, aralkyl , (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl;

Optionally, R ⁴ and R ⁵ combined with the nitrogen attached to them represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiomorpholino, acridino Heptinyl or perhydro-1,4-diazepan-1-yl, each of which is optionally substituted by one or more groups selected from the group consisting of lower alkyl, Hydroxy, lower alkoxy lower alkyl, aromatic, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocycle base-alkyl; and

n is an integer of 0-3;

With the proviso that when R is unsubstituted indol-3-yl, ^R1 is other than _-NH2 . In another preferred embodiment, the present invention relates to compounds represented by the following structural formula and physiologically acceptable salts thereof:

in:

R is selected from substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzene Indole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole;

R ¹ is hydrogen or -AZ;

A is -(CH ₂ ) _n -, (CH ₂ ) _n NH-, -(CH ₂ ) _n O-, -(CH ₂ ) _n S-, -(CH ₂ ) _n S(O)- or -( CH ₂ ) _n S(O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC(O)-, -NR ⁴ R ⁵ , -C(O)NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring system selected from the following group: C ₃ -C ₆ cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole and their N-oxides, wherein the ring system can optionally be Substituted by one or more groups selected from the group consisting of halogen, lower alkyl, R ³ O-, HO-, HOC(O)-, R ³ OC(O)-, trihalomethyl, nitro , Aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl, heterocyclyl-alkyl, -CN, - C(O)NR ⁴ R ⁵ or -NR ⁴ R ⁵ ;

Each occurrence of R ³ is independently selected from substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aryl Alkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl;

Each occurrence of ^R4 and ^R5 independently of each other is hydrogen or is selected from substituted or unsubstituted: lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl, heterocyclyl, aralkyl , (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl; Optionally, R ⁴ and R ⁵ combined with the nitrogen attached to them represent morpholino, pyrrolidino, Piperidino group, imidazol-1-yl, piperazino group, thiomorpholino, azepin group or perhydrogenated-1,4-diazepan-1-yl, each of which Optionally substituted with one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C ₃ -C ₆ )cycloalkyl, heterocycle radical, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl; and

n is an integer of 0-3;

requirement is:

When R is unsubstituted indol-3-yl, R ¹ is not -NH ₂ ; and

When R is substituted or unsubstituted benzene or unsubstituted imidazole, 1,2,3-triazole, 1,2,4-triazole, pyridine, pyrimidine, pyrazine, pyrrole, pyrazole, oxazole or thiazole , R ¹ is not lower alkyl, (C ₃ -C ₆ )cycloalkyl, benzene or -C(O)NR ⁴ R ⁵ , wherein R ⁴ and R ⁵ are independently H, lower alkyl or carbocyclic aromatic base.

In another preferred embodiment, the present invention relates to compounds represented by the following structural formula and physiologically acceptable salts thereof:

in:

R is selected from substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetrahydroindole, benzene Indole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrrole, pyrazole, oxazole and thiazole;

R ¹ is hydrogen or -AZ;

A is -(CH ₂ ) _n -, (CH ₂ ) _n NH-, -(CH ₂ ) _n O-, -(CH ₂ ) _n S-, -(CH ₂ ) _n S(O)- or -( CH ₂ ) _n S(O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC(O)-, -NR ⁴ R ⁵ , -C(O)NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring system selected from the following group: C ₃ -C ₆ cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole and their N-oxides, wherein the ring system can optionally be Substituted by one or more groups selected from the group consisting of halogen, lower alkyl, R ³ O-, HO-, HOC(O)-, R ³ OC(O)-, trihalomethyl, nitro , Aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl, heterocyclyl-alkyl, -CN, - C(O)NR ⁴ R ⁵ or -NR ⁴ R ⁵ ;

Each occurrence of R ³ is independently selected from substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aryl Alkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl;

Each occurrence of ^R4 and ^R5 independently of each other is hydrogen or is selected from substituted or unsubstituted: lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl, heterocyclyl, aralkyl , (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl;

Optionally, R ⁴ and R ⁵ combined with the nitrogen attached to them represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiomorpholino, acridino Heptinyl or perhydro-1,4-diazepan-1-yl, each of which is optionally substituted by one or more groups selected from the group consisting of lower alkyl, Hydroxy, lower alkoxy lower alkyl, aromatic, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocycle base-alkyl; and

n is an integer of 0-3;

requirement is:

a) R is not pyrrol-3-yl or pyrrol-3-yl substituted by alkyl or carbocyclic aryl;

b) R is not indol-3-yl or indol-3-yl substituted by alkyl or carbocyclic aryl; and

c) R is not an azaindole or an azaindole substituted at the 2-position with an alkyl or carbocyclic aryl.

In another preferred embodiment, the present invention relates to compounds represented by the following structural formula and physiologically acceptable salts thereof:

in:

R is substituted pyrrole or is selected from substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetra Indoline, benzoindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrazole, oxazole and thiazole;

R ¹ is hydrogen or -AZ;

A is -(CH ₂ ) _n -, (CH ₂ ) _n NH-, -(CH ₂ ) _n O-, -(CH ₂ ) _n S-, -(CH ₂ ) _n S(O)- or -( CH ₂ ) _n S(O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC(O)-, -NR ⁴ R ⁵ , -C(O)NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring system selected from the following group: C ₃ -C ₆ cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole and their N-oxides, wherein the ring system can optionally be Substituted by one or more groups selected from the group consisting of halogen, lower alkyl, R ³ O-, HO-, HOC(O)-, R ³ OC(O)-, trihalomethyl, nitro , Aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl, heterocyclyl-alkyl, -CN, - C(O)NR ⁴ R ⁵ or -NR ⁴ R ⁵ ;

Each occurrence of R ³ is independently selected from: lower alkyl, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ ) cycloalkyl-alkyl and heterocyclyl-alkyl;

Each occurrence of ^R4 and ^R5 independently of each other is hydrogen or is selected from substituted or unsubstituted: lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl, heterocyclyl, aralkyl , (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl;

Optionally, R ⁴ and R ⁵ combined with the nitrogen attached to them represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiomorpholino, acridino Heptinyl or perhydro-1,4-diazepan-1-yl, each of which is optionally substituted by one or more groups selected from the group consisting of lower alkyl, Hydroxy, lower alkoxy lower alkyl, aromatic, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocycle base-alkyl; and

n is an integer of 0-3;

requirement is:

a) When R is a substituted pyrrole, the pyrrole is replaced by R ³ OC(O)R ⁶ , R ³ OR ⁶ -, trihalomethyl, trihalomethylcarbonyl, -(CH ₂ ) _p -R ⁷ , -O(CH ₂ ) _p R ⁷ , -C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -C(O)O(CH ₂ ) _p R ⁷ , -OC(O)(CH ₂ ) _p R ⁷ , -N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ N(R ⁴ )-R ⁶ -R ⁷ , -R ⁶ N(R ⁶ -R ⁷ ) ₂ , R ⁶ C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -R ⁶ C(O)O(CH ₂ ) _p R ⁷ , -R ⁶ OC( O)(CH ₂ ) _p R ⁷ , -R ⁶ N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ CH(C(O)OR ⁴ )(N(R ⁴ )C( O) R ⁴ ), substituted aryl or aralkyl substituted, wherein each occurrence of R ⁶ is independently lower alkyl or aryl;

Each occurrence of ^R is independently alkoxy, haloalkyl, lower alkylpiperazine, hydroxyl, ^{R3O- , R3C} (O)-, or ^NR4R3 ; and

p is an integer of 1-3;

b) When R is indol-3-yl, the indol-3-yl is substituted by the following groups: R ³ OC(O)R ⁶ , R ³ OR ⁶ , trihalomethyl, trihaloform Carbonyl, -(CH ₂ ) _p -R ⁷ , -O(CH ₂ ) _p R ⁷ , -C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -C(O)O(CH ₂ ) _p R ⁷ , -OC(O)(CH ₂ ) _p R ⁷ , -N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ N(R ⁴ )-R ⁶ -R ⁷ , -R ⁶ N(R ⁶ -R ⁷ ) ₂ , R ⁶ C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -R ⁶ C(O)O( CH ₂ ) _p R ⁷ , -R ⁶ OC(O)(CH ₂ ) _p R ⁷ , -R ⁶ N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ CH(C(O )OR ⁴ )(N(R ⁴ )C(O)R ⁴ ), substituted aryl or aralkyl, and

c) When R is pyrazol-3-yl, the pyrazol-3-yl is substituted by the following groups: R ³ OC(O)R ⁶ , R ³ OR ⁶ , trihalomethyl, trihaloform Carbonyl, -(CH ₂ ) _p -R ⁷ , -O(CH ₂ ) _p R ⁷ , -C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -C(O)O(CH ₂ ) _p R ⁷ , -OC(O)(CH ₂ ) _p R ⁷ , -N(R ⁴ )C(O)(CH ₂ ) _P R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ N(R ⁴ )-R ⁶ -R ⁷ , -R ⁶ N(R ⁶ -R ⁷ ) ₂ , R ⁶ C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -R ⁶ C(O)O( CH ₂ ) _p R ⁷ , -R ⁶ OC(O)(CH ₂ ) _p R ⁷ , -R ⁶ N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ CH(C(O )OR ⁴ )(N(R ⁴ )C(O)R ⁴ ), substituted aryl or aralkyl.

In another preferred embodiment, the present invention relates to compounds represented by the following structural formula and physiologically acceptable salts thereof:

in:

R is substituted pyrrole or is selected from substituted or unsubstituted: indole, imidazole, 1,2,3-triazole, 1,2,4-triazole, benzimidazole, 4,5,6,7-tetra Indoline, benzoindole, azaindole, indazole, pyridine, quinoline, pyrimidine, benzene, pyrazine, pyrazole, oxazole and thiazole;

R ¹ is hydrogen or -AZ;

A is -(CH ₂ ) _n -, -(CH ₂ ) _n NH-, -(CH ₂ ) _n O-, -(CH ₂ ) _n S-, -(CH ₂ ) _n S(O)-, or - (CH ₂ ) _n S(O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ OC(O)-, -NR ⁴ R ⁵ , -C(O)NR ⁴ R ⁵ , R ³ CO-, R ³ O- or a ring system selected from the following group: C ₃ -C ₆ cycloalkane, isoxazole, isothiazole, imidazole, benzene, pyrrole, indole, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran, thiophene, imidazole, furan, triazine, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole and their N-oxides, wherein the ring system can optionally be Substituted by one or more groups selected from the group consisting of halogen, lower alkyl, R ³ O-, HO-, HOC(O)-, R ³ OC(O)-, trihalomethyl, nitro , Aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl, heterocyclyl-alkyl, -CN, - C(O)NR ⁴ R ⁵ or -NR ⁴ R ⁵ ;

Each occurrence of R ³ is independently selected from substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aryl Alkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl;

Each occurrence of ^R4 and ^R5 independently of each other is hydrogen or is selected from substituted or unsubstituted: lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl, heterocyclyl, aralkyl , (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl;

Optionally, R ⁴ and R ⁵ combined with the nitrogen attached to them represent morpholino, pyrrolidino, piperidino, imidazol-1-yl, piperazino, thiomorpholino, acridino Heptinyl or perhydro-1,4-diazepan-1-yl, each of which is optionally substituted by one or more groups selected from the group consisting of lower alkyl, Hydroxy, lower alkoxy lower alkyl, aromatic, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocycle base-alkyl; and

n is an integer of 0-3;

requirement is:

a) when R is unsubstituted indol-3-yl, R ¹ is not -NH ₂ ;

b) when R is substituted or unsubstituted benzene or unsubstituted imidazole, 1,2,3-triazole, 1,2,4-triazole, pyridine, pyrimidine, pyrazine, pyrrole, pyrazole, oxazole or When thiazole; R ¹ is not lower alkyl, (C ₃ -C ₆ ) cycloalkyl, benzene or -C (O) NR ⁴ R ⁵ , wherein R ⁴ and R ⁵ are independently H, lower alkyl or carbon Cycloaryl;

c) R is not pyrrol-3-yl or pyrrol-3-yl substituted by alkyl or carbocyclic aryl;

d) R is not indol-3-yl or indol-3-yl substituted by alkyl or carbocyclic aryl;

e) R is not an azaindole or an azaindole substituted at the 2-position by an alkyl or carbocyclic aryl;

f) When R is a substituted pyrrole, the pyrrole is substituted by the following groups: R ³ OC(O)R ⁶ , R ³ OR ⁶ , trihalomethyl, trihalomethylcarbonyl, -(CH ₂ ) _p -R ⁷ , -O(CH ₂ ) _p R ⁷ , -C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -C(O)O(CH ₂ ) _p R ⁷ , -OC( O)(CH ₂ ) _p R ⁷ , -N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ N(R ⁴ )-R ⁶ -R ⁷ , -R ⁶ N(R ⁶ -R ⁷ ) ₂ , R ⁶ C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -R ⁶ C(O)O(CH ₂ ) _p R ⁷ , - R ⁶ OC(O)(CH ₂ ) _p R ⁷ , -R ⁶ N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ CH(C(O)OR ⁴ )(N(R ⁴ ) C(O)R ⁴ ), substituted aryl or aralkyl, wherein

Each occurrence of ^R is independently lower alkyl or aryl;

Each occurrence of ^R7 is independently alkoxy, haloalkyl, lower alkylpiperazine, hydroxyl, ^{R3O- , R3C} (O)-, or ^NR4R5 ; and

p is an integer of 1-3;

g) When R is indol-3-yl, the indol-3-yl is substituted by the following groups: R ³ OC(O)R ⁶ , R ³ OR ⁶ -, trihalomethyl, trihalo Methylcarbonyl, -(CH ₂ ) _p -R ⁷ , -O(CH ₂ ) _p R ⁷ , -C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -C(O)O(CH ₂ ) _p R ⁷ , -OC(O)(CH ₂ ) _p R ⁷ , -N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ N( R ⁴ )-R ⁶ -R ⁷ , -R ⁶ N(R ⁶ -R ⁷ ) ₂ , R ⁶ C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -R ⁶ C(O)O (CH ₂ ) _p R ⁷ , -R ⁶ OC(O)(CH ₂ ) _p R ⁷ , -R ⁶ N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ CH(C( O)OR ⁴ )(N(R ⁴ )C(O)R ⁴ ), substituted aryl or aralkyl, and

h) When R is pyrazol-3-yl, the pyrazol-3-yl is substituted by the following groups: R ³ OC(O)R ⁶ , R ³ OR ⁶ -, trihalomethyl, trihalo Methylcarbonyl, -(CH ₂ ) _p -R ⁷ , -O(CH ₂ ) _p R ⁷ , -C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -C(O)O(CH ₂ ) _p R ⁷ , -OC(O)(CH ₂ ) _p R ⁷ , -N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ N( R ⁴ )-R ⁶ -R ⁷ , -R ⁶ N(R ⁶ -R ⁷ ) ₂ , R ⁶ C(O)N(R ⁴ )(CH ₂ ) _p R ⁷ , -R ⁶ C(O)O (CH ₂ ) _p R ⁷ , -R ⁶ OC(O)(CH ₂ ) _p R ⁷ , -R ⁶ N(R ⁴ )C(O)(CH ₂ ) _p R ⁷ , -R ⁶ CH(C( O)OR ⁴ )(N(R ⁴ )C(O)R ⁴ ), substituted aryl or aralkyl.

In a more preferred embodiment, the invention relates to any of the aforementioned compounds, wherein A is -NH-, -O-, -S-, -S(O)- or -S(O) ₂ -; and Z is cyclopropane , 3-pyridyl or pyrazinyl.

In another more preferred embodiment, the invention relates to any of the aforementioned compounds, wherein A is -O-; and Z is ethyl, n-propyl or isopropyl.

In another more preferred embodiment, the present invention relates to any of the aforementioned compounds, wherein A is _-CH2- ; and Z is phenyl, wherein said phenyl is optionally replaced by one or more groups selected from Substitution: Halogen, trihalomethyl, hydroxyl, -NR ⁴ R ⁵ , nitro, -CONR ⁴ R ⁵ , lower alkyl, R ³ O-, -C(O)OR ⁴ and -OC(O)R ⁴ .

In another more preferred embodiment, the present invention relates to any of the aforementioned compounds, wherein R are independently substituted by one or more groups selected from the group consisting of halogen, lower alkyl, R ³ O-, hydroxyl, HOC ( O)-, R ³ OC(O)-, R ³ OC(O)R ⁶ , R ³ OR ⁶ , trihalomethyl, trihalomethylcarbonyl, nitro, -C(O)NR ⁴ R ⁵ , -NR ⁴ R ⁵ , R ³ CO-, -(CH ₂ ) _n -R ⁷ , -C(O)(CH ₂ ) _n -R ⁷ , -C(O)-(CH ₂ ) _n -C (O)-R ⁷ , -O(CH ₂ ) _n R ⁷ , -C(O)NR ⁴ (CH ₂ ) _n R ⁷ , C(O)O(CH ₂ ) _n R ⁷ , -OC(O) (CH ₂ ) _n R ⁷ , -NR ⁴ C(O)(CH ₂ ) _n R ⁷ , -R ⁶ NR ⁴ R ⁵ , -R ⁶ N(R ⁴ )-R ⁶ -R ⁷ , -R ⁶ N (R ⁶ -R ⁷ ) ₂ , -R ⁶ C(O)NR ⁴ (CH ₂ ) _n R ⁷ , -R ⁶ C(O)O(CH ₂ ) _n R ⁷ , -R ⁶ OC(O)( CH ₂ ) _n R ⁷ , R ⁶ NR ⁴ C(O)(CH ₂ ) _n R ⁷ , -R ⁶ CH(C(O)OR ⁴ )(NR ⁵ C(O)R ⁴ ) and optionally substituted Aryl and optionally substituted aralkyl. Optionally substituted aryl and optionally substituted aralkyl are optionally substituted with one or more substituents selected from the group consisting of halogen, trihalomethyl, hydroxyl, -NR ⁴ R ⁵ , nitro, - CONR ⁴ R ⁵ , lower alkyl, R ³ O-, C(O)OR ⁴ or -OC(O)R ³ . R ⁶ is lower alkyl or aryl. R ⁷ is alkoxy, haloalkyl, lower alkylpiperazine, hydroxyl, R ³ O-, R ³ C(O)- or -NR ⁴ R ³ . In one aspect of this embodiment, R is pyrrolyl, indolyl, azaindolyl, phenyl, pyrazolyl, imidazolyl, thienyl, 4,5,6,7-tetrahydroindolyl or quinolinyl. In another aspect of this embodiment, R is pyrrol-2-yl, pyrrol-3-yl, indol-2-yl, indol-3-yl, azaindol-3-yl, pyrazole- 4-yl, imidazol-2-yl, imidazol-4-yl, thien-2-yl or quinolin-5-yl.

In yet another preferred embodiment, the present invention relates to any of the aforementioned compounds, wherein ^R is trifluoromethyl, amino, cyclopropylamino, methyl, ethyl, propyl, isopropyl, cyclopropyl, 2- Methylcyclopropyl, 2,2,3,3-tetramethylcyclopropyl, 2-phenylcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -(CH ₂ ) _p -O-benzene base, -(CH ₂ ) _p -O-(4-methoxyphenyl), -(CH ₂ ) _p -O-(4-chlorophenyl), -(CH ₂ ) _p -O-(4-methyl phenylphenyl), -(CH ₂ ) _p -O-(3-methylphenyl), -(CH ₂ ) _p -O-(4-phenylphenyl), -(CH ₂ ) _p -O- (4-hydroxyphenyl), -(CH ₂ ) _p -O-(4-nitrophenyl), -(CH ₂ ) _p -O-(4-aminophenyl), -(CH ₂ ) _p - O-(4-carbamoylphenyl), -(CH ₂ ) _p -O-(4-methoxycarbonylphenyl), -NH-phenyl, -NH-(4-methoxyphenyl), - NH-(4-chlorophenyl), -NH-(4-fluorophenyl), -NH-(4-isopropylphenyl), isopropoxy, ethoxy, cyclopentyloxy, -( CH ₂ ) _p -indolyl, -(CH ₂ ) _p -pyridyl, -(CH ₂ ) _p -benzothiazolyl, -(CH ₂ ) _p -pyrrolyl, -(CH ₂ ) _p -tetrahydrofuranyl , -(CH ₂ ) _p -pyrazinyl, -(CH ₂ ) _p -furyl, -(CH ₂ ) _p -thienyl, -(CH ₂ ) _p -phenyl, -(CH ₂ ) _p -iso Oxazolyl, -(CH ₂ ) _p -(5-methylisoxazolyl), -(CH ₂ ) _p -pyrimidinyl, -(CH ₂ ) _p -pyridazinyl, -(CH ₂ ) _n -C(O)-OMe, -( _CH2 ) _n -C(O)-OEt, or benzyl optionally substituted with one or more Cl, F, OMe, methyl or amino. P is an integer of 1-3. In one aspect of this embodiment, R is optionally substituted with one or more groups selected from the group consisting of Br, Cl, F, aminomethyl, N,N-dimethylaminomethyl, carboxy, carboxymethyl Carboxyethyl, carbonylmethyl, carbonylethyl, methoxycarbonyl, ethoxycarbonyl, phenyl, 4-morpholinomethyl, -C(O)-O-(CH ₂ ) ₂ -N(Me ) ₂ , -C(O)-O-(CH ₂ ) ₂ -N(Et) ₂ , -C(O)-O-CH ₂ -N(Me) ₂ , -C(O)-O-(CH ₂ ) ₂ -N(Me) ₂ , -C(O)-NH-(CH ₂ ) ₂ -N(Me) ₂ , -CH ₂ -NH-C(O)-CF ₃ and any optional Substituted moieties: methyl, ethyl, propyl, isopropyl, butyl, and phenyl, wherein the optionally substituted moieties are optionally replaced by one or more of Br, Cl, F, hydroxy, nitro Substituted by radical, amino or lower alkyl.

In another aspect, the invention provides pharmaceutical compositions comprising one or more compounds of the invention as defined herein in association with a pharmaceutically acceptable carrier or diluent.

In another aspect, the present invention provides a method for inhibiting the activity of one or more protein kinases, the method comprising administering a compound represented by the following formula and its physiologically acceptable salts and biologically active metabolites:

in:

R is selected from substituted or unsubstituted: aliphatic, aromatic, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkane and heterocyclyl-alkyl;

R ¹ is hydrogen or -AZ;

R ² is hydrogen or is selected from substituted or unsubstituted: lower alkyl, aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aralkyl, (C ₃ -C ₆ )cycloalkane Base-alkyl, heterocyclyl-alkyl;

A is -(CH ₂ ) _n -, -(CH ₂ ) _n NH-, -(CH ₂ ) _n O-, -(CH ₂ ) _n S-, -(CH ₂ ) _n S(O)-, or - (CH ₂ ) _n S(O) ₂ -;

Z is -H, lower alkyl, aralkyl, trihalomethyl, trihalomethylcarbonyl, R ³ CO-, R ³ OC(O)-, -NR ⁴ R ⁵ , -C(O) NR ⁴ R ⁵ , R ³ O- or a ring system selected from the group consisting of (C ₃ -C ₆ )cycloalkyl, benzene, pyrrole, isoxazole, isothiazole, indole, pyridine, pyrazine, pyrimidine , benzothiazole, tetrahydrofuran, thiophene, triazine, imidazole, furan, benzimidazole, pyridazine, quinoxaline, pyrazole, oxazole, thiazole and N-oxides thereof, wherein the ring system can be optionally Substituted by one or more groups selected from the group consisting of halogen, lower alkyl, R ³ O-, HO-, HOC(O)-, R ³ OC(O)-, trihalomethyl, nitrate Base, aryl, -CN, -C(O)NR ⁴ R ⁵ and -NR ⁴ R ⁵ ;

Each occurrence of R ³ is independently selected from substituted or unsubstituted: lower alkyl, lower alkoxy lower alkyl, aromatic group, (C ₃ -C ₆ )cycloalkyl, heterocyclyl, aryl Alkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl;

Each occurrence of ^R4 and ^R5 independently of each other is hydrogen or is selected from substituted or unsubstituted: lower alkyl, aromatic group, (C ₃ -C ₆ ) cycloalkyl, heterocyclyl, aralkyl , (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl; Optionally, R ⁴ and R ⁵ combined with the nitrogen attached to them represent morpholino, pyrrolidino, Piperidino group, imidazol-1-yl, piperazino group, thiomorpholino, azepin group or perhydrogenated-1,4-diazepan-1-yl, each of which Optionally substituted with one or more groups selected from the group consisting of lower alkyl, hydroxy, lower alkoxy lower alkyl, aromatic, (C ₃ -C ₆ )cycloalkyl, heterocycle radical, aralkyl, (C ₃ -C ₆ )cycloalkyl-alkyl and heterocyclyl-alkyl; and

n is an integer of 0-3.

Preferred of the above methods are those wherein a protein kinase is inhibited in a subject in need thereof.

Preferred methods of any of the above methods are those wherein the compound is a mixture of stereoisomers.

A preferred method of any of the above methods is one in which the stereoisomers are enantiomers.

A preferred method of any of the above methods is one wherein the stereoisomers are the E and Z isomers.

Preferred methods of any of the above methods are those wherein the compound is a mixture of structural isomers.

A preferred method of any of the above methods is one wherein the structural isomers are tautomers.

A preferred method of any of the above methods is wherein the protein kinase is a receptor tyrosine kinase or a non-receptor tyrosine kinase.

A preferred method in any of the above methods is wherein the tyrosine kinase is selected from the group consisting of KDR, Flt-1, TIE-2, FGFR, PDGFR, IGF-1-R, c-Met, Lck, Src, fyn, Lyn, Blk and yes.

In another aspect, the invention relates to a method of treating or substantially inhibiting a hyperproliferative or inflammatory disease in a subject in need thereof, the method comprising administering to said subject any compound of the invention as defined herein.

In another aspect, the invention relates to a method of treating or inhibiting angiogenesis in a subject in need thereof, the method comprising administering to said subject any compound of the invention as defined herein.

In another aspect, the invention relates to a method of inducing an anti-angiogenic effect in a subject in need thereof, the method comprising administering to said subject any compound of the invention as defined herein.

In another aspect, the present invention relates to a method of treating or inhibiting the progress of a disease or condition in a subject in need thereof, the method comprising administering to said subject any compound of the invention as defined herein, wherein said disease or condition is selected from cancer, joint inflammation, atherosclerosis, restenosis, psoriasis, hemangioma, myocardial angiogenesis, coronary and scoliosis, ischemic extremity angiogenesis, corneal disease, flushing, neovascular glaucoma, macular degeneration, wound healing, digestion Ulcers, diseases associated with Helicobacter, angiogenic diseases caused by viruses, bone fractures, diabetic retinopathy, Crohn's disease, inflammatory bowel disease, fever from cat scratches, retinopathy or precocious puberty, ulcers, thyroid Hyperplasia, burns, trauma, acute lung injury, chronic lung disease, stroke, polyps, cysts, synovitis, chronic and allergic inflammation, ovarian hyperstimulation syndrome, pulmonary and cerebral edema, keloids, fibrosis, cirrhosis , carpal tunnel syndrome, sepsis, adult respiratory distress syndrome, multiple organ dysfunction syndrome, ascites and effusions associated with tumors, and edema.

In another aspect, the invention relates to a method of affecting the development of vascular hyperpermeability or edema in a subject in need thereof, the method comprising administering to said subject any compound of the invention as defined herein. Preferred methods are those wherein the effect on edema is anti-edema.

A preferred method of any of the above methods is wherein the protein kinase is a serine kinase.

A preferred method of any of the above methods is wherein the protein kinase is threonine kinase.

Particularly preferred compounds of the invention are:

3-cyclopropyl-4-{[(3,5-dimethyl-4-(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-2-pyrazole Lin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-piperidinomethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-diethanolaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-(4-methyl-1-piperazinylmethyl)-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazole Lin-5-one,

3-cyclopropyl-4-[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-(3,5-dibromo-4-hydroxybenzylidene)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-cyclopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[4-(2-dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[4-(2-dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-ethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[3-(2-dimethylaminoethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[3-(2-dimethylaminoethylaminocarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,4-diethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-cyclopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-{[(3,5-Dimethyl-4-[(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-(3-pyridyl)- 2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-[(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazoline-5 -ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-diethanolaminomethyl-3,5-dimethyl-pyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3-diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-{[3-(4-Methyl-1-piperazinylmethyl)-4,5-tetramethylenepyrrol-2-yl]methylene}-3-(3-pyridyl)-2 -pyrazolin-5-one,

3-(3-pyridyl)-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazoline- 5-keto,

4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one ,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one ,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-(3,5-dibromo-4-hydroxybenzylidene)-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-bromopyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-(3-pyridyl-2-pyrazolin-5-one,

3-(3-pyridyl)-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3,4-diethoxycarbonylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-(3-pyridyl)-2-pyrazolin-5-one ,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazoline-5 -ketone,

4-[(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one ,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-{[(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-isopropoxy-2- pyrazolin-5-one,

4-[(3,5-Dimethyl-4-[(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one ,

4-[(4-diethylaminomethyl-3,5-dimethyl-pyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(piperidinomethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-diethanolaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3-diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-{[3-(4-methyl-1-piperazinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrrole oxazolin-5-one,

3-isopropoxy-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazoline-5- ketone,

3-isopropoxy-4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-(3,5-Dibromo-4-hydroxybenzylidene)-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-Bromopyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,4-diethoxycarbonylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-isopropoxy-2-pyrazolin-5-one,

4-[(5-Ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one ,

4-[(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-[[(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-ethoxy-2-pyrrole oxazolin-5-one,

4-[(3,5-Dimethyl-4-[(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(4-diethylaminomethyl-3,5-dimethyl-pyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(piperidinomethylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(4-diethanolaminomethyl-3,5-dimethyl-pyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

3-ethoxy-4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3-diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

3-ethoxy-4-{[3-(4-methyl-1-piperazinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazole Lin-5-one,

3-ethoxy-4-{[[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazoline-5- ketone,

3-ethoxy-4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-(3,5-Dibromo-4-hydroxybenzylidene)-3-ethoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

3-ethoxy-4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

3-ethoxy-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

3-ethoxy-4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-ethoxy-4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-ethoxy-4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-ethoxy-4-[(5-methoxyindol-2-yl)methylene]-2-pyrazolin-5-one,

4-[3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-3-ethoxy-2-pyrazolin-5-one,

3-ethoxy-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-ethoxy-2-pyrazolin-5-one,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-ethoxy-2-pyrazolin-5-one,

4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-(4-Methyl-1-piperazinylmethyl)-4,5-tetramethylenepyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

3-pyrazinyl-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazolin-5-one ,

4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-(3,5-Dibromo-4-hydroxybenzylidene)-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-Bromopyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

3-pyrazinyl-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one ,

4-[(Indol-3-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(1-methylindol-3-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

3-pyrazinyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(Indol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,4-Diethoxycarbonylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-bromopyrrol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[(5-methoxyindol-2-yl)methylene]-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-3-(imidazol-2-yl)-2-pyrazoline -5-keto,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazoline -5-keto,

3-(imidazol-2-yl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(imidazol-2-yl)-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,4-diethoxycarbonylpyrrol-2-yl)methylene]-3-(imidazol-2-yl))-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-(imidazol-2-yl)-2-pyrazoline-5- ketone,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-(imidazol-2-yl)-2-pyrazolin-5-one,

4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazoline- 5-keto,

4-[(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(imidazol-2-yl)-2-pyrazoline-5- ketone,

4-[(4-bromopyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

3-(1-methylcyclopropyl)-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

3-(1-methylcyclopropyl)-4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(1-methylcyclopropyl)-4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(1-methylcyclopropyl)-4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-(1-methylcyclopropyl)-4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

3-(1-methylcyclopropyl)-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[(5-methoxyindol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

3-(1-methylcyclopropyl)-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-3-(1-methylcyclopropyl)-2-pyrrole oxazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrrole oxazolin-5-one,

4-[(indol-3-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[(pyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[(indol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazolin-5-one,

4-[(3,4-diethoxycarbonylpyrrol-2-yl)methylene]-3-(1-methylcyclopropyl))-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-(1-methylcyclopropyl)-2-pyrazoline- 5-keto,

4-{[3-(2-Amino-2-carboxyethyl)indol-2-yl]methylene}-3-(1-methylcyclopropyl)-2-pyrazolin-5-one ,

4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazole Lin-5-one,

4-[(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(1-methylcyclopropyl)-2-pyrazoline- 5-keto,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-(2-furyl)-2- pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(1-pyrrolidinylmethyl)pyrrol-2-yl]methylene}-3-(2-furyl)-2-pyrazoline-5 -ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene}-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(4-diethanolaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3-Diethylaminoethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-{[3-(4-methyl-1-piperazinylmethyl)-4,5-tetramethylenepyrrol-2-yl]methylene}-2 -pyrazolin-5-one,

3-(2-furyl)-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazoline- 5-keto,

3-(2-furyl)-4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one ,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one ,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-(3,5-dibromo-4-hydroxybenzylidene)-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-2-pyrazolin-5-one,

3-(2-furyl)-4-[(4-dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-bromopyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(2-furyl)-4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(2-furyl)-4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-(2-furyl)-4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(5-methoxyindol-2-yl)methylene]-2-pyrazolin-5-one,

3-(2-furyl)-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-3-(2-furyl)-2-pyrazoline- 5-keto,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazoline- 5-keto,

3-(2-furyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-(2-furyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(2-furyl)-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,4-diethoxycarbonylpyrrol-2-yl)methylene]-3-(3-(2-furyl))-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-(2-furyl)-2-pyrazolin-5-one ,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-(2-furyl)-2-pyrazolin-5-one,

4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazoline-5 -ketone,

4-[(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one ,

4-[(3,5-Dimethyl-4-[(morpholinomethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one ,

4-[(3,5-Dimethyl-4-(4-methyl-1-piperazinyl)methylpyrrol-2-yl]methylene}-3-(2-thienyl)-2- pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazoline-5- ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-diethanolaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3-diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3-(4-Methyl-1-piperazinylmethyl)-4,5-tetramethylenepyrrol-2-yl]methylene}-3-(2-thienyl)-2 -pyrazolin-5-one,

4-{[3-(1-pyrrolidinylmethyl)-4,5-tetramethylenepyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazoline- 5-keto,

4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one ,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one ,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-(3,5-dibromo-4-hydroxybenzylidene)-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-oxo-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-bromopyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

3-(2-thienyl)-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(1-methylindol-3-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(5-methoxyindol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazoline- 5-keto,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazoline- 5-keto,

4-[(indol-3-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(pyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(indol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,4-Diethoxycarbonylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-(2-thienyl)-2-pyrazolin-5-one ,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazoline-5 -ketone,

4-[(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one ,

4-[(4-bromopyrrol-2-yl)methylene]-3-cyclopropoxy-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-cyclopropoxy-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-cyclopropoxy-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[4-(2-dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[4-(2-dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(3-ethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[3-(2-dimethylaminoethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[3-(2-dimethylaminoethylaminocarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(3,5-dimethyl-4-ethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[3,5-dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(5-methoxyindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[3,5-dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-2-pyrazolin-5-one ,

3-cyclopropoxy-4-{[3,5-dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl)methylene]-2-pyrazoline-5- ketone,

3-cyclopropoxy-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(3,4-diethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-cyclopropoxy-2-pyrazolin-5-one,

4-{[3-(2-Amino-2-carboxyethyl)indol-2-yl]methylene}-3-cyclopropoxy-2-pyrazolin-5-one,

3-cyclopropoxy-4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one ,

4-[(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-cyclopropoxy-2-pyrazolin-5-one,

4-[(4-bromopyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

3-[2-(5-pyrimidinylethyl)]-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one ,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one ,

4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-[3-(4-Morpholinoethoxycarbonylindol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one ,

4-[3-(4-Morpholinoethylaminocarbonylindol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one ,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazoline-5- ketone,

4-[(1-methylindol-3-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-[3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazoline-5- ketone,

4-[(5-methoxyindol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

3-[2-(5-pyrimidinylethyl)]-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-3-[2-(5-pyrimidinylethyl)]- 2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]- 2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

3-[2-(5-pyrimidinylethyl)]-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-[(3,4-diethoxycarbonylpyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-[2-(5-pyrimidinylethyl)]-2-pyridine oxazolin-5-one,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-[2-(5-pyrimidinylethyl)]-2-pyrazoline- 5-keto,

4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2 -pyrazolin-5-one,

4-[(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-[2-(5-pyrimidinylethyl)]-2-pyrrole oxazolin-5-one,

4-[(4-bromopyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

3-(2-phenylethyl)-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[(1-methylindol-3-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[(5-methoxyindol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

3-(2-phenylethyl)-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-3-(2-phenylethyl)-2-pyrazoline -5-keto,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazoline -5-keto,

4-[(indol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[(3,4-Diethoxycarbonylpyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-(2-phenylethyl)-2-pyrazoline-5- ketone,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-(2-phenylethyl)-2-pyrazolin-5-one,

4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazoline- 5-keto,

4-[(5-Chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-(2-phenylethyl)-2-pyrazoline-5- ketone,

4-[(4-bromopyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazolin-5-one,

3-[2-(4-hydroxyphenyl)ethyl]-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazolin-5-one,

4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazolin-5-one ,

4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazolin-5-one ,

4-[(3-ethoxycarbonylindol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazolin-5-one,

4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazoline-5- ketone,

4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazoline-5- ketone,

3-[2-(4-Hydroxyphenyl)ethyl]-4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one ,

3-[2-(4-Hydroxyphenyl)ethyl]-4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one ,

3-[2-(4-Hydroxyphenyl)ethyl]-4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-2-pyrazoline-5- ketone,

3-[2-(4-Hydroxyphenyl)ethyl]-4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-2-pyrazoline-5- ketone,

4-[3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazoline-5 -ketone,

3-[2-(4-Hydroxyphenyl)ethyl]-4-[(5-methoxyindol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-hydroxyphenyl)ethyl]-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-3-[2-(4-hydroxyphenyl)ethyl] -2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl] -2-pyrazolin-5-one,

4-[(3,4-diethoxycarbonylpyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-[2-(4-hydroxyphenyl)ethyl]-2- pyrazolin-5-one,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-[2-(4-hydroxyphenyl)ethyl]-2-pyrazoline -5-keto,

4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]- 2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-3-[2-(4-hydroxyphenyl)ethyl]-2- pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-[(4-bromopyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-[(4-chloropyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-[(5-chloropyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-[(5-trifluoromethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-Aminophenyl)ethyl]-4-[4-(2-Dimethylaminoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one ,

3-[2-(4-Aminophenyl)ethyl]-4-[4-(2-Dimethylaminoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one ,

3-[2-(4-aminophenyl)ethyl]-4-[(3-ethoxycarbonylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-Aminophenyl)ethyl]-4-[3-(2-Dimethylaminoethoxycarbonylindol-2-yl)methylene]-2-pyrazoline-5- ketone,

3-[2-(4-Aminophenyl)ethyl]-4-[3-(2-Dimethylaminoethylaminocarbonylindol-2-yl)methylene]-2-pyrazoline-5- ketone,

3-[2-(4-aminophenyl)ethyl]-4-[4-(4-morpholinoethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one ,

3-[2-(4-aminophenyl)ethyl]-4-[4-(4-morpholinoethylaminocarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one ,

3-[2-(4-aminophenyl)ethyl]-4-[3-(4-morpholinoethoxycarbonylindol-2-yl)methylene]-2-pyrazoline-5- ketone,

3-[2-(4-aminophenyl)ethyl]-4-[3-(4-morpholinoethylaminocarbonylindol-2-yl)methylene]-2-pyrazoline-5- ketone,

3-[2-(4-aminophenyl)ethyl]-4-[(5-methoxyindol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-{[3,5-dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene} -2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-{[3,5-dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl]methylene} -2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-[(3,4-diethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3-(2-Acetamido-2-methoxycarbonylethyl)indol-2-yl]methylene}-3-[2-(4-aminophenyl)ethyl]-2- pyrazolin-5-one,

4-{[3-(2-amino-2-carboxyethyl)indol-2-yl]methylene}-3-[2-(4-aminophenyl)ethyl]-2-pyrazoline -5-keto,

3-[2-(4-aminophenyl)ethyl]-4-[(5-ethoxy-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]- 2-pyrazolin-5-one,

3-[2-(4-aminophenyl)ethyl]-4-[(5-chloro-4-methoxycarbonylmethyl-3-methoxycarbonylpyrrol-2-yl)methylene]-2- pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-{[(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-(4-pyrimidinyl)- 2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazoline-5- ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(piperidinomethylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-diethanolaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3-diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-{[3-(4-Methyl-1-piperazinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2 -pyrazolin-5-one,

3-(4-pyrimidinyl)-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazoline- 5-keto,

4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(4-pyrimidinyl)pyrazolin-5-one,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-(3,5-dibromo-4-hydroxybenzylidene)-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-{[(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-(5-pyrimidinyl)- 2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazoline-5- ketone,

4-[(3,5-Dimethyl-4-diethylaminomethylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(piperidinomethylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-diethanolaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3-diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-{[3-(4-Methyl-1-piperazinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2 -pyrazolin-5-one,

3-(5-pyrimidinyl)-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazoline- 5-keto,

4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-(3,5-Dibromo-4-hydroxybenzylidene)-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-{[(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-(2-pyrimidinyl)- 2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazoline-5- ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(piperidinomethylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-diethanolaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3-diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-{[3-(4-Methyl-1-piperazinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2 -pyrazolin-5-one,

3-(2-pyrimidinyl)-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazoline- 5-keto,

4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-(3,5-dibromo-4-hydroxybenzylidene)-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-{[(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-(3-pyridazinyl) -2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazoline-5 -ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one ,

4-[(4-diethanolaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one ,

4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one ,

4-[(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one ,

4-{[3-(4-Methyl-1-piperazinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-3-(3-pyridazinyl)- 2-pyrazolin-5-one,

3-(3-pyridazinyl)-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazoline -5-keto,

4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazoline-5- ketone,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazoline-5- ketone,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-(3,5-dibromo-4-hydroxybenzylidene)-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one ,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-{[(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-(4-pyridazinyl) -2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazoline-5 -ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(piperidinomethylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazoline-5- ketone,

4-[(4-diethanolaminomethyl-3,5-dimethyl-pyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one ,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one ,

4-[(3-Morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one ,

4-[(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one ,

4-{[3-(4-Methyl-1-piperazinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-3-(4-pyridazinyl)- 2-pyrazolin-5-one,

3-(4-pyridazinyl)-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazoline -5-keto,

4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazoline-5- ketone,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazoline-5- ketone,

4-[(4-diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-(3,5-Dibromo-4-hydroxybenzylidene)-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one ,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazolin-5-one ,

4-[(3,5-Dimethyl-4-{[(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-(5-isoxazolyl )-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-[(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazoline -5-keto,

4-[(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazolin-5-one ,

4-[(4-diethanolaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazolin-5-one ,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazoline-5- ketone,

3-(5-isoxazolyl)-4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazoline-5- ketone,

4-[(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazoline-5- ketone,

3-(5-isoxazolyl)-4-{[3-(4-methyl-1-piperazinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene} -2-pyrazolin-5-one,

3-(5-isoxazolyl)-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene}-2-pyrazole Lin-5-one,

3-(5-isoxazolyl)-4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazoline-5 -ketone,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazoline-5 -ketone,

4-[(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazolin-5-one ,

4-(3,5-Dibromo-4-hydroxybenzylidene)-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazoline-5- ketone,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2-pyrazole Lin-5-one,

4-[(3,5-Dimethyl-4-{[(4-methyl-1-piperazinylmethyl)pyrrol-2-yl]methylene}-3-(5-methyl-3 -isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-[(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)- 2-pyrazolin-5-one,

4-[(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2-pyrazole Lin-5-one,

4-[(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2-pyrrole oxazolin-5-one,

4-[(4-diethanolaminomethyl-3,5-dimethyl-pyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2-pyrrole oxazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2-pyrrole oxazolin-5-one,

3-(5-methyl-3-isoxazolyl)-4-[(3-morpholinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrrole oxazolin-5-one,

4-[(3-Diethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2-pyrrole oxazolin-5-one,

3-(5-methyl-3-isoxazolyl)-4-{[3-(4-methyl-1-piperazinyl)methyl-4,5-tetramethylenepyrrol-2-yl ]methylene}-2-pyrazolin-5-one,

3-(5-Methyl-3-isoxazolyl)-4-{[3-(1-pyrrolidinyl)methyl-4,5-tetramethylenepyrrol-2-yl]methylene} -2-pyrazolin-5-one,

3-(5-methyl-3-isoxazolyl)-4-[(3-piperidinomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2- pyrazolin-5-one,

4-[(4-Dimethylamino-4,5,6,7-tetrahydroindol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2- pyrazolin-5-one,

4-[(4-Diethylaminoethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2-pyrazole Lin-5-one,

4-(3,5-dibromo-4-hydroxybenzylidene)-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2-pyrazole Lin-5-one,

3-(5-methyl-3-isoxazolyl)-4-[(4-oxo-1,5,6,7-tetrahydroindol-2-yl)methylene]-2-pyridine oxazolin-5-one,

4-[(4-Dimethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2-pyrazoline-5 -ketone,

3-cyclopropyl-4-(1-3-[(dimethylamino)methyl]-4,5,6,7-tetrahydro-1H-2-indolylmethylene)-4,5- Dihydro-1H-5-pyrazolone,

3-cyclopropyl-4-(1-4-[(1,1-dimethylammonium)methyl]-3,5-dimethyl-1H-2-pyrrolylmethylene)-4,5 - Dihydro-1H-5-pyrazolone maleate,

4-[1-(4-[[2-(Dimethylamino)ethyl](methyl)amino]methyl-3,5-dimethyl-1H-2-pyrrolyl)methylene]-3 -(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,

4-(1-4-[2-(diethylamino)ethyl]-3,5-dimethyl-1H-2-pyrrolylmethylene)-3-(2-pyrazinyl)-4, 5-dihydro-1H-5-pyrazolone,

4-1-[4-(3-Chloropropionyl)-3,5-dimethyl-1H-2-pyrrolyl]methylene-3-(2-pyrazinyl)-4,5-dihydro -1H-5-pyrazolone,

4-(1-3-[(Dimethylamino)methyl]-4,5,6,7-tetrahydro-1H-2-indolylmethylene)-3-(2-pyrazinyl)- 4,5-dihydro-1H-5-pyrazolone,

4-(1-4-[(dimethylamino)methyl]-3,5-dimethyl-1H-2-pyrrolylmethylene)-3-(5-methyl-3-isoxazolyl )-4,5-dihydro-1H-5-pyrazolone,

3-cyclopropyl-4-[(4,5-dimethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-benzyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-methoxyphenoxymethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-phenoxymethyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-chlorophenoxymethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-methoxybenzyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-Benzyl-4-{[4-(2-carboxyethyl)-3-methylpyrrol-2-yl]methylene}-2-pyrazolin-5-one,

3-Benzyl-4-{[3-(2-carboxyethyl)-4-methylpyrrol-2-yl]methylene}-2-pyrazolin-5-one,

3-(4-methylphenoxymethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

2-amino-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-phenethyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-anilino-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-methylbenzyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-methylanilino)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-methoxyanilino)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-chlorobenzyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-Chloroanilino)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(3-chlorophenoxymethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(indol-3-yl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(3-methoxybenzyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(3,4-dimethoxybenzyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-methoxyphenethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-phenylphenoxymethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(2-phenylpropyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(3-phenylpropyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-hydroxyphenethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethylpyrrol-2-yl)methylene]-3-phenethyl-2-pyrazolin-5-one,

3-(4-methylphenethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-ethoxy-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-nitrophenethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-fluoroanilino)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-chlorophenethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4,5-Dimethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-phenethyl-2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl)pyrrol-2-yl]methylene}-3-isopropoxy-2-pyrazolin-5-one,

3-cyclopentyloxy-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-tert-butylureido-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[(4-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-aminophenethyl)-4-[(4-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[(1-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[(5-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-aminophenethyl)-4-[(3,5-dimethyl-4-ethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-ethoxy-4-[(5-methylpyrrol-2-yl)methylene]2-pyrazolin-5-one,

3-(4-carbamoylphenethyl)-4-[(3,5-dimethyl-4-ethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-(4-methoxycarbonylphenethyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-(4-aminophenethyl)-4-[(3,5-dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(5-Ethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-(4-hydroxyphenethyl)-2-pyrazolin-5-one,

3-(ethoxycarbonylmethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-Methoxyanilinocarbonylmethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{(3-(2-carboxyethyl)-4-methylpyrrol-2-yl]methylene}-3-isopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclobutyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(3-pyridyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[[1-(3,5-dichlorophenyl)pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(pyrrol-2-yl)methylene]-3-(2,2,3,3-tetramethylcyclopropyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopentyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(2-methylcyclopropyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-(benzothiazol-2-yl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4,5-Dimethylpyrrol-2-yl)methylene]-4-(3-pyridyl)]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-ethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(pyrrol-2-yl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(benzothiazol-2-yl)-4-[(4-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(5-methylpyrrol-2-yl)methylene]-3-(-3-pyridyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-ethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[(5-phenylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-Propyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-methyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-isopropylanilino)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(3-phenylamino)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-{[1-(4-hydroxybutyl)pyrrol-2-yl]methylene]-2-pyrazolin-5-one,

4-{[4-(2-carboxyethyl)-3-methylpyrrol-2-yl]methylene}-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-carboxy-3,5-dimethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-acetyl-3,5-dimethylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-3-isopropoxy-2-pyrazoline-5- ketone,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl]methylene}-3-isopropoxy-2-pyrazoline-5- ketone,

4-[(5-ethoxycarbonylpyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(5-carboxypyrrol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-(4-Chloroanilinocarbonylmethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-phenylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-(tetrahydrofuran-3-yl)-2-pyrazolin-5-one,

4-[(4-carboxy-3,5-dimethylpyrrol-2-yl)methylene]-3-cyclopropyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,4-Dimethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-carboxyethyl)-3-methylpyrrol-2-yl]methylene}-3-cyclopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-ethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(2-Methoxycarbonylethyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-ethoxycarbonyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(trans-2-phenylcyclopropyl)-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclohexyl-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropylamino-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-morpholinomethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(5-carboxypyrrol-2-yl)methylene]-3-cyclopropyl-2-pyrazolin-5-one,

4-[(4-chloropyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(4-Bromopyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(5-chloropyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4[(4-chloropyrrol-2-yl)methylene]-3-cyclopropyl-2-pyrazolin-5-one,

4-[(4-Bromopyrrol-2-yl)methylene]-3-cyclopropyl-2-pyrazolin-5-one,

3-pyrazinyl-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(3-pyridyl)-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-carboxy-3,5-dimethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-{[3,5-dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-2-pyrazolin-5-one ,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one maleate,

4-{[3,5-Dimethyl-4-(2-morpholinoethylaminocarbonyl)pyrrol-2-yl]methylene-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethylpyrrol-2-yl)methylene]-3-(2-pyridyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-(2-pyridyl)-2-pyrazolin-5-one,

4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-3-(2-pyridyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-trifluoroacetylaminomethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-aminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(benzothiazol-2-yl)-4-[(3,5-dimethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-(benzothiazol-2-yl)-4-[(3,5-dimethyl-4-morpholinomethylpyrrol-2-yl)methylene]-2-pyrazoline-5- ketone,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-carboxypyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-diethanolaminomethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-trifluoroacetylaminomethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-ethoxycarbonyl-3-phenylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(1-pyrrolidinylmethyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-phenyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethylpyrrol-2-yl)methylene]-3-phenyl-2-pyrazolin-5-one,

4-[(3,4-bis(ethoxycarbonyl)pyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

3-ethoxy-4-[(4-ethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(2-pyridylethyl)-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(1-methyl-2-phenylethyl)-2-pyrazoline-5 -ketone,

4-[(4-carboxy-3,5-dimethylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

3-ethoxy-4-[(5-nitropyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-ethoxy-4-[(4-nitropyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(4-carboxypyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl)pyrrol-2-yl)methylene}-3-ethoxy-2-pyrazolin-5-one ,

4-[(5-chloro-3-methoxycarbonyl-4-methoxycarbonylmethylpyrrol-2-yl)methylene-3-ethoxy-2-pyrazolin-5-one,

4-{[3-(2-carboxyethyl)-4-methylpyrrol-2-yl)methylene}-3-ethoxy-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

3-ethoxy-4-[(4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-trifluoromethyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

3-(3-aminophenyl)-4-[(3,5-dimethyl-4-ethoxycarbonylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-ethoxy-4-{[2-(4-morpholinoethyl)aminocarbonylpyrrol-2-yl]methylene}-2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl-3-phenylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(4-Methyl-1-piperazinylmethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-piperidinomethylpyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazoline-5- ketone,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(5-isoxazolyl)-2-pyrazolin-5-one ,

4-[(5-methyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-Dimethyl-4-[N-(2-dimethylaminoethyl)-N-methylaminomethylpyrrol-2-yl}methylene}-3-pyrazinyl- 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethyl-4,5-tetramethylenepyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one maleate,

4-{[4-(3-chloropropionyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-Diethylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminomethylpyrrol-2-yl)methylene]-3-(5-methyl-3-isoxazolyl)-2-pyrazole Lin-5-one,

4-{[3,5-Dimethyl-4-(4-hydroxypiperidinomethyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-[(4-Aminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one maleate,

4-{[4-(4-Benzylpiperidino)methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-hydroxyethyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-Dimethyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

3-cyclopropyl-4-{{3,5-dimethyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-2-pyrazoline- 5-keto,

3-cyclopropyl-4-{[3,5-dimethyl-4-(2-hydroxyethyl)pyrrol-2-yl]methylene}-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-ethylaminoethyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(3-Diethylaminopropyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(3-hydroxypropyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-Dimethyl-4-dimethylaminoacetylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one hydrochloride,

4-[(3,5-Dimethyl-4-dimethylaminoacetylpyrrol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

3-cyclopropyl-4-{[(2-diethylaminoethyl)-3,5-dimethyl-4-pyrrol-2-yl]methylene}-2-pyrazolin-5-one ,

4-{[3,5-Dimethyl-4-(2-dimethylaminoethyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(4-hydroxybutyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(4-diethylaminobutyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-Diethylaminoethyl-N-oxide)-3,5-dimethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[3,5-Dimethyl-4-(1-pyrrolidinylacetyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-Diethylaminoacetyl-3,5-dimethylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-[3-(1-pyrrolidinylpropyl)]pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-[(Dimethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(dimethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-ethoxyoxalyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

3-benzyl-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-Benzyl-4-{[1-(4-hydroxybutyl)indol-3-yl]methylene}-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-methoxyphenoxymethyl)-2-pyrazolin-5-one,

4-[(Indol-3-yl)methylene]-3-phenoxymethyl-2-pyrazolin-5-one,

3-(4-chlorophenoxymethyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-methoxybenzyl)-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-methylphenoxymethyl)-2-pyrazolin-5-one,

4-[(Indol-3-yl)methylene]-3-phenethyl-2-pyrazolin-5-one,

4-[(Indol-3-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-methylbenzyl)-2-pyrazolin-5-one,

4-[(Indol-3-yl)methylene]-3-anilino-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-methylanilino)-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-methoxyanilino)-2-pyrazolin-5-one,

3-(4-chlorobenzyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)indol-3-yl]methylene}-3-(4-methoxybenzyl)-2-pyrazolin-5-one,

3-(4-Chloroanilino)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(3-methoxybenzyl)-2-pyrazolin-5-one,

3-(3,4-dimethoxybenzyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-(4-Hydroxybenzyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-(3-Chlorophenoxymethyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-(indol-3-yl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-methoxyphenethyl)-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-phenylphenoxymethyl)-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(2-phenylpropyl)-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(3-phenylpropyl)-2-pyrazolin-5-one,

3-(4-Hydroxyphenethyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-methylphenethyl)-2-pyrazolin-5-one,

3-ethoxy-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)indol-3-yl]methylene}-3-isopropoxy-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)indol-3-yl]methylene}-3-phenethyl-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-nitrophenethyl)-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-propoxy-2-pyrazolin-5-one,

3-(4-fluoroanilino)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-(4-aminophenethyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[(2-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[(7-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(7-methylindol-3-yl)methylene]-3-phenethyl-2-pyrazolin-5-one,

3-cyclopentyl-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-methoxycarbonylphenethyl)-2-pyrazolin-5-one,

3-isopropoxy-4-[(1-isopropylindol-3-yl)methylene]-2-pyrazolin-5-one,

3-(4-hydroxyphenethyl)-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

3-isopropyl-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-(4-Chloroanilinocarbonylmethyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-ethoxycarbonylmethyl-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-methoxyanilinocarbonylmethyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

3-(2-Aminocarbonylethyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-cyclobutyl-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-(2-Dimethylaminocarbonylethyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-{[1-(4-hydroxybutyl)indol-3-yl]methylene}-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(4-pyridyl)-2-pyrazolin-5-one,

3-cyclopentyl-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(2,2,3,3-tetramethylcyclopropyl)-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(2-methylcyclopropyl)-2-pyrazolin-5-one,

3-cyclohexyl-4-{[1-(4-hydroxybutyl)indol-3-yl]methylene}-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)indol-3-yl]methylene}-3-(4-pyridyl)-2-pyrazolin-5-one,

3-(Benzothiazol-2-yl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(2-pyridyl)-2-pyrazolin-5-one,

3-Dimethylamino-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(pyrrol-2-yl)-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(6-methoxybenzothiazol-2-yl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(7-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(1-methylindol-3-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(Indol-3-yl)methylene]-3-propyl-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-methyl-2-pyrazolin-5-one,

4-[(Indol-3-yl)methylene]-3-trifluoromethyl-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)indol-3-yl]methylene}-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)indol-3-yl]methylene}-3-methyl-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)indol-3-yl]methylene}-3-trifluoromethyl-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)indol-3-yl]methylene}-3-(tert-butyl)-2-pyrazolin-5-one,

3-ethoxycarbonyl-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(2-methoxycarbonylethyl)-2-pyrazolin-5-one,

4-[(indol-3-yl)methylene]-3-(trans-2-phenyl-1-cyclopropyl)-2-pyrazolin-5-one,

3-cyclobutyl-4-{[1-(4-hydroxybutyl)indol-3-yl]methylene}-2-pyrazolin-5-one,

4-[(6-carboxy-1-methylindol-3-yl)methylene]-3-cyclopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-methoxy-1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(1-methylindol-3-yl)methylene[-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(1,7-dimethylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(1-methylindol-3-yl)methylene]-3-(tetrahydrofuran-3-yl)-2-pyrazolin-5-one,

3-cyclopropylamino-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(6-carboxy-1-methylindol-3-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(1,7-Dimethylindol-3-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[(5-methoxy-1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

3-(4-fluoroanilino)-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(1-methylindol-3-yl)methylene]-3-trifluoroacetylamino-2-pyrazolin-5-one,

3-(4-aminophenethyl)-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

3-amino-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

3-(4-chlorophenethyl)-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one,

3-ethoxy-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

3-(5-isoxazolyl)-4-[(1-methylindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(1-methylindol-3-yl)methylene]-3-tert-butyl-2-pyrazolin-5-one,

4-[(6-carboxy-1-methylindol-3-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{{1-methyl-6-[2-(4-morpholino)ethyl]aminocarbonylindol-3-yl}methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-[(Indol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-(4-hydroxyphenethyl)-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-aminophenethyl)-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-methoxycarbonylphenethyl)-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

3-(4-carbamoylphenethyl)-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-dimethylaminomethylindol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-2-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

3-isopropoxy-4-[(5-methoxyindol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[(1-methylindol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-2-yl)methylene]-3-(tetrahydrofuran-3-yl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-methoxyindol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-nitroindol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(Indol-2-yl)methylene]-3-isopropylamino-2-pyrazolin-5-one,

3-(4-carboxyphenethyl)-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(indol-2-yl)methylene]-3-phenyl-2-pyrazolin-5-one,

3-isopropoxy-4-[(3-methylindol-2-yl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-{[3-(2-methoxycarbonyl-2-acetylaminoethyl)indol-2-yl]methylene}-2-pyrazolin-5-one,

3-ethoxy-4-[(indol-2-yl)methylene]-2-pyrazolin-5-one,

3-ethoxy-4-{[3-(4-morpholinomethyl)indol-2-yl]methylene}-2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-(4-morpholinomethyl)indol-2-yl]methylene}-2-pyrazolin-5-one,

4-[(5-methoxyindol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(5-methoxyindol-2-yl)methylene]-3-(2-pyridyl)-2-pyrazolin-5-one,

4-[(4-Chloro-6,7-dihydroindol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(4-chloro-6,7-dihydroindol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-dihydroindol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-Dimethylaminomethylindol-2-yl)methylene]-3-ethoxy-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-benzyl-2-pyrazolin-5-one,

3-Benzyl-4-{[1-(4-hydroxybutyl)-7-azaindol-3-yl]methylene}-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-(4-methoxyphenoxymethyl)-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-amino-4-[(7-azaindol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-(4-methoxybenzyl)-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-anilino-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-(4-methylbenzyl)-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-(4-hydroxyphenethyl)-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)-7-azaindol-3-yl]methylene}-3-(4-hydroxyphenethyl)-2-pyrazolin-5-one ,

4-[(7-azaindol-3-yl)methylene]-3-isopropyl-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-cyclopropyl-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-cyclobutyl-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-phenyl-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-(4-fluoroanilino)-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-propyl-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-methyl-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-trifluoromethyl-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-(tert-butyl)-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)-7-azaindol-3-yl]methylene}-3-trifluoromethyl-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-(4-isopropylanilino)-2-pyrazolin-5-one,

4-[(7-azaindol-3-yl)methylene]-3-(3-methylanilino)-2-pyrazolin-5-one,

4-{[1-(4-Hydroxybutyl)-7-azaindol-3-yl]methylene}-3-(3-methylanilino)-2-pyrazolin-5-one ,

4-[(7-azaindol-3-yl)methylene]-3-phenethyl-2-pyrazolin-5-one,

3-benzyl-4-[(4-dimethylaminophenyl)methylene]-2-pyrazolin-5-one,

4-[(4-Dimethylaminophenyl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-Dimethylaminophenyl)methylene]-3-phenethyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-dimethylaminophenyl)methylene]-2-pyrazolin-5-one,

3-isopropoxy-4-[(3-methylpyrazol-4-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-methylpyrazol-4-yl)methylene]-2-pyrazolin-5-one,

4-[(imidazol-2-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-cyclopropyl-4-[(imidazol-2-yl)methylene]-2-pyrazolin-5-one,

4-[(imidazol-4-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

3-cyclopropyl-4-[(thiophen-2-yl)methylene]-2-pyrazolin-5-one,

4-[(Indol-3-yl)methylene]-3-isopropyl-1-methyl-2-pyrazolin-5-one,

3-isopropoxy-4-[(pyrrol-3-yl)methylene]-2-pyrazolin-5-one,

4-[(8-hydroxyquinolin-5-yl)methylene]-3-isopropoxy-2-pyrazolin-5-one,

4-{[4-(2-Diethylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrazoline-5 -ketone,

4-{[4-(2-Diethylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2-pyrazoline- 5-keto,

4-{[4-(2-Diethylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(2-furyl)-2-pyrazoline-5 -ketone,

4-{[4-(2-Diethylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazoline-5 -ketone,

4-{[4-(2-Diethylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrazoline-5 -ketone,

4-{[4-(2-Diethylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrazoline-5 -ketone,

4-{[4-(2-Diethylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2-pyrazoline- 5-keto,

3-cyclopropyl-4-[(3,5-dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-{[4-(2-cyclopropylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-2-pyrazolin-5-one ,

3-cyclopropyl-4-{[3,5-dimethyl-4-(2-phenylaminoethyl)pyrrol-2-yl]methylene}-2-pyrazolin-5-one,

3-cyclopropyl-4-{{3,5-dimethyl-4-[2-(4-pyridylmethylamino)ethyl]pyrrol-2-yl}methylene}-2-pyrazoline -5-keto,

4-{[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-cyclopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-{[4-(1-pyrrolidinylmethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-2-pyrazoline-5 -ketone,

3-cyclopropyl-4-{{3-isopropyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-2-pyr oxazolin-5-one,

3-cyclopropyl-4-{[4-(2-cyclopropylaminoethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-2-pyrazoline- 5-keto,

3-cyclopropyl-4-{{4-[3-(1-pyrrolidinyl)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-2-pyrrole oxazolin-5-one,

3-cyclopropyl-4-{[3-isopropyl-5-methyl-4-(4-piperidinobutyl)pyrrol-2-yl]methylene}-2-pyrazoline- 5-keto,

3-cyclopropyl-4-{{4-[3-(4-pyridylmethylamino)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-2- pyrazolin-5-one,

3-cyclopropyl-4-{{4-(4-dimethylaminobutyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-2-pyrazoline-5 -ketone,

3-cyclopropyl-4-[(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl)methylene]-2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-cyclopropyl-4-(1-pyrrolidinylmethyl)-5-methylpyrrol-2-yl]methylene}-2-pyrazoline-5 -ketone,

3-cyclopropyl-4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidinyl)ethyl]pyrrol-2-yl}methylene}-2-pyr oxazolin-5-one,

3-cyclopropyl-4-{{3-cyclopropyl-4-[2-di(methoxyethyl)aminoethyl]-5-methylpyrrol-2-yl}methylene}-2 -pyrazolin-5-one,

3-cyclopropyl-4-{[3-cyclopropyl-4-(3-diethylaminopropyl)-5-methylpyrrol-2-yl]methylene}-2-pyrazoline-5 -ketone,

3-cyclopropyl-4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidinyl)propyl]-5-methylpyrrol-2-yl} Methylene}-2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-cyclopropyl-5-methyl-4-(3-phenylmethylaminopropyl)pyrrol-2-yl]methylene}-2-pyrazoline- 5-keto,

3-cyclopropyl-4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidinyl)butyl]pyrrol-2-yl}methylene}-2-pyr oxazolin-5-one,

3-cyclopropyl-4-{[3-cyclopropyl-5-methyl-4-(4-cyclobutylaminobutyl)pyrrol-2-yl]methylene}-2-pyrazoline- 5-keto,

4-{[4-(2-cyclopropylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{[3,5-Dimethyl-4-(2-phenylaminoethyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-Dimethyl-4-[2-(4-pyridylmethylamino)ethyl]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(1-pyrrolidinylmethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{3-isopropyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

3-pyrazinyl-4-{{4-[3-(1-pyrrolidinyl)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-2-pyr oxazolin-5-one,

4-{[3-isopropyl-5-methyl-4-(4-piperidinobutyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

3-pyrazinyl-4-{{4-[3-(4-pyridylmethylamino)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-2- pyrazolin-5-one,

4-{[4-(4-Dimethylaminobutyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-[(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidinyl)ethyl]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{{3-cyclopropyl-4-[2-di(methoxyethyl)aminoethyl]-5-methylpyrrol-2-yl}methylene}-2-pyrazinyl-2 -pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylaminopropyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidinyl)propyl]-5-methylpyrrol-2-yl}methylene}-3 -pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenylmethylaminopropyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidinyl)butyl]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(4-cyclobutylaminobutyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazoline-5- ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazolin-5-one,

4-[4-(2-cyclopropylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(2-furyl)-2-pyrazoline-5 -ketone,

4-{[3,5-Dimethyl-4-(2-ethylaminoethyl)-pyrrol-2-yl]methylene}-3-(2-furyl)-2-pyrazoline-5 -ketone,

4-{[3,5-Dimethyl-4-(2-phenylaminoethyl)pyrrol-2-yl]methylene}-3-(2-furyl)-2-pyrazoline-5- ketone,

4-{{3,5-Dimethyl-4-[2-(4-pyridylmethylamino)ethyl]pyrrol-2-yl}methylene}-3-(2furyl)-2-pyridine oxazolin-5-one,

4-[(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazoline-5- ketone,

4-{[4-(1-pyrrolidinylmethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(2-furyl)-2-pyrazole Lin-5-one,

4-{[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(2-furyl)-2-pyrazolin-5-one ,

4-{{3-isopropyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-(2-furyl)- 2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(2-furyl)-2-pyrrole oxazolin-5-one,

3-(2-furyl)-4-{{4-[3-(1-pyrrolidinyl)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}- 2-pyrazolin-5-one,

3-(2-furyl)-4-{[3-isopropyl-5-methyl-4-(4-piperidinobutyl)pyrrol-2-yl]methylene}-2-pyridine oxazolin-5-one,

3-(2-furyl)-4-{{4-[3-(4-pyridylmethylamino)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene} -2-pyrazolin-5-one,

4-{[4-(4-Dimethylaminobutyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(2furyl)-2-pyrazoline -5-keto,

4-[(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(2-furyl)-2-pyrazoline-5- ketone,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidinyl)ethyl]pyrrol-2-yl}methylene}-3-(2-furyl)- 2-pyrazolin-5-one,

4-{3-cyclopropyl-4-[2-di(methoxyethyl)aminoethyl]-5-methylpyrrol-2-yl}methylene}-3-(2-furyl) -2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylaminopropyl)-5-methylpyrrol-2-yl]methylene}-3-(2furyl)-2-pyrazoline -5-keto,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidinyl)propyl]-5-methylpyrrol-2-yl}methylene}-3 -(2-furyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenylmethylaminopropyl)pyrrol-2-yl]methylene}-3-(2-furyl)-2-pyrrole oxazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidinyl)butyl]pyrrol-2-yl}methylene}-3-(2-furyl)- 2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(4-cyclobutylaminobutyl)pyrrol-2-yl]methylene}-3-(2-furyl)-2-pyr oxazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazoline-5- ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazoline- 5-keto,

4-{[3,5-Dimethyl-4-(2-ethylaminoethyl)-pyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazoline-5 -ketone,

4-{[3,5-Dimethyl-4-(2-phenylaminoethyl)pyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazoline-5- ketone,

4-{{3,5-Dimethyl-4-[2-(4-pyridylmethylamino)ethyl]pyrrol-2-yl}methylene}-3-(2-thienyl)-2- pyrazolin-5-one,

4-{[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazolin-5-one ,

4-[(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazoline-5- ketone,

4-{[4-(1-pyrrolidinylmethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazole Lin-5-one,

4-{{3-isopropyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-(2-thienyl)- 2-pyrazolin-5-one,

4-{[4-(2-Cyclopropylaminoethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrrole oxazolin-5-one,

4-{{4-[3-(1-pyrrolidinyl)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-3-(2-thienyl)- 2-pyrazolin-5-one,

4-{[3-isopropyl-5-methyl-4-(4-piperidinobutyl)pyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrrole oxazolin-5-one,

4-{{4-[3-(4-pyridylmethylamino)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-3-(2-thienyl) -2-pyrazolin-5-one,

4-{[4-(4-Dimethylaminobutyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazole Lin-5-one,

4-[(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(2-thienyl)-2-pyrazoline-5- ketone,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidinyl)ethyl]pyrrol-2-yl}methylene}-3-(2-thienyl)- 2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-di(methoxyethyl)aminoethyl]-5-methylpyrrol-2-yl}methylene}-3-(2-thienyl )-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylaminopropyl)-5-methylpyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrazole Lin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidinyl)propyl]-5-methylpyrrol-2-yl}methylene}-3 -(2-thienyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenylmethylaminopropyl)pyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrrole oxazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidinyl)butyl]pyrrol-2-yl}methylene}-3-(2-thienyl)- 2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(4-cyclobutylaminobutyl)pyrrol-2-yl]methylene}-3-(2-thienyl)-2-pyrrole oxazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazoline-5- ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrazoline- 5-keto,

4-{[3,5-Dimethyl-4-(2-ethylaminoethyl)-pyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrazoline-5 -ketone,

4-{[3,5-Dimethyl-4-(2-phenylaminoethyl)pyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrazoline-5- ketone,

4-{{3,5-Dimethyl-4-[2-(4-pyridylmethylamino)ethyl]pyrrol-2-yl}methylene}-3-(4-pyrimidinyl)-2- pyrazolin-5-one,

4-{[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazoline-5- ketone,

4-{[4-(1-pyrrolidinylmethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrazole Lin-5-one,

4-{{3-isopropyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-(4-pyrimidinyl)- 2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrrole oxazolin-5-one,

3-(4-pyrimidinyl)-4-{{4-[3-(1-pyrrolidinyl)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}- 2-pyrazolin-5-one,

4-{[3-isopropyl-5-methyl-4-(4-piperidinobutyl)pyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrrole oxazolin-5-one,

4-{{4-[3-(4-pyridylmethylamino)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-3-(4-pyrimidinyl) -2-pyrazolin-5-one,

4-{[4-(4-Dimethylaminobutyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrazole Lin-5-one,

4-[(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(4-pyrimidinyl)-2-pyrazoline-5- ketone,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidinyl)ethyl]pyrrol-2-yl}methylene}-3-(4-pyrimidinyl)- 2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-di(methoxyethyl)aminoethyl]-5-methylpyrrol-2-yl}methylene}-3-(4-pyrimidinyl )-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylaminopropyl)-5-methylpyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrazole Lin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidinyl)propyl]-5-methylpyrrol-2-yl}methylene}-3 -(4-pyrimidinyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenylmethylaminopropyl)pyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrrole oxazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidinyl)butyl]pyrrol-2-yl}methylene}-3-(4-pyrimidinyl)- 2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(4-cyclobutylaminobutyl)pyrrol-2-yl]methylene}-3-(4-pyrimidinyl)-2-pyrrole oxazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazoline-5- ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrazoline- 5-keto,

4-{[3,5-Dimethyl-4-(2-ethylaminoethyl)-pyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrazoline-5 -ketone,

4-{[3,5-Dimethyl-4-(2-phenylaminoethyl)pyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrazoline-5- ketone,

4-{{3,5-Dimethyl-4-[2-(4-pyridylmethylamino)ethyl]pyrrol-2-yl}methylene}-3-(5-pyrimidinyl)-2- pyrazolin-5-one,

4-{[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazoline-5- ketone,

4-{[4-(1-pyrrolidinylmethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrazole Lin-5-one,

4-{{3-isopropyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-(5-pyrimidinyl)- 2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrrole oxazolin-5-one,

3-(5-pyrimidinyl)-4-{{4-[3-(1-pyrrolidinyl)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}- 2-pyrazolin-5-one,

4-{[3-isopropyl-5-methyl-4-(4-piperidinobutyl)pyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrrole oxazolin-5-one,

4-{{4-[3-(4-pyridylmethylamino)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-3-(5-pyrimidinyl) -2-pyrazolin-5-one,

4-{{4-(4-Dimethylaminobutyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrazole Lin-5-one,

4-[(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(5-pyrimidinyl)-2-pyrazoline-5- ketone,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidinyl)ethyl]pyrrol-2-yl}methylene}-3-(5-pyrimidinyl)- 2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-di(methoxyethyl)aminoethyl]-5-methylpyrrol-2-yl}methylene}-3-(5-pyrimidinyl )-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylaminopropyl)-5-methylpyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrazole Lin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidinyl)propyl]-5-methylpyrrol-2-yl}methylene}-3 -(5-pyrimidinyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenylmethylaminopropyl)pyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyrrole oxazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidinyl)butyl]pyrrol-2-yl}methylene}-3-(5-pyrimidinyl)- 2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(4-cyclobutylaminobutyl)pyrrol-2-yl]methylene}-3-(5-pyrimidinyl)-2-pyr oxazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazoline-5- ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrazoline- 5-keto,

4-{[3,5-Dimethyl-4-(2-ethylaminoethyl)-pyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrazoline-5 -ketone,

4-{[3,5-Dimethyl-4-(2-phenylaminoethyl)pyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrazoline-5- ketone,

4-{{3,5-Dimethyl-4-[2-(4-pyridylmethylamino)ethyl]pyrrol-2-yl}methylene}-3-(2-pyrimidinyl)-2- pyrazolin-5-one,

4-{[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrazolin-5-one ,

4-[(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazoline-5- ketone,

4-{[4-(1-pyrrolidinylmethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrazole Lin-5-one,

4-{{3-isopropyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-(2-pyrimidinyl)- 2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrrole oxazolin-5-one,

3-(2-pyrimidinyl)-4-{{4-[3-(1-pyrrolidinyl)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}- 2-pyrazolin-5-one,

4-{[3-isopropyl-5-methyl-4-(4-piperidinobutyl)pyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrrole oxazolin-5-one,

4-{{4-[3-(4-pyridylmethylamino)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-3-(2-pyrimidinyl) -2-pyrazolin-5-one,

4-{[4-(4-Dimethylaminobutyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrazole Lin-5-one,

4-[(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(2-pyrimidinyl)-2-pyrazoline-5- ketone,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidinyl)ethyl]pyrrol-2-yl}methylene}-3-(2-pyrimidinyl)- 2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-di(methoxyethyl)aminoethyl]-5-methylpyrrol-2-yl}methylene}-3-(2-pyrimidinyl )-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylaminopropyl)-5-methylpyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrazole Lin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidinyl)propyl]-5-methylpyrrol-2-yl}methylene}-3 -(2-pyrimidinyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenylmethylaminopropyl)pyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrrole oxazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidinyl)butyl]pyrrol-2-yl}methylene}-3-(2-pyrimidinyl)- 2-pyrazolin-5-one,

4-[3-cyclopropyl-5-methyl-4-(4-cyclobutylaminobutyl)pyrrol-2-yl]methylene}-3-(2-pyrimidinyl)-2-pyrazole Lin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazoline-5 -ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2-pyrazoline -5-keto,

4-{[3,5-Dimethyl-4-(2-ethylaminoethyl)-pyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2-pyrazoline- 5-keto,

4-{[3,5-Dimethyl-4-(2-phenylaminoethyl)pyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2-pyrazoline-5 -ketone,

4-{{3,5-Dimethyl-4-[2-(4-pyridylmethylamino)ethyl]pyrrol-2-yl}methylene}-3-(3-pyridazinyl)-2 -pyrazolin-5-one,

4-{[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2-pyrazoline-5- ketone,

4-[(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazoline-5 -ketone,

4-{[4-(1-pyrrolidinylmethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2-pyrrole oxazolin-5-one,

4-{{3-isopropyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-(3-pyridazinyl) -2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2- pyrazolin-5-one,

3-(3-pyridazinyl)-4-{{4-[3-(1-pyrrolidinyl)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene} -2-pyrazolin-5-one,

4-{[3-isopropyl-5-methyl-4-(4-piperidinobutyl)pyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2- pyrazolin-5-one,

4-{{4-[3-(4-pyridylmethylamino)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-3-(3-pyridazinyl )-2-pyrazolin-5-one,

4-{[4-(4-Dimethylaminobutyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2-pyridine oxazolin-5-one,

4-[(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(3-pyridazinyl)-2-pyrazoline-5 -ketone,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidinyl)ethyl]pyrrol-2-yl}methylene}-3-(3-pyridazinyl) -2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-di(methoxyethyl)aminoethyl]-5-methylpyrrol-2-yl}methylene}-3-(3-pyridazine Base) -2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylaminopropyl)-5-methylpyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2-pyridine oxazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidinyl)propyl]-5-methylpyrrol-2-yl}methylene}-3 -(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenylmethylaminopropyl)pyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2- pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidinyl)butyl]pyrrol-2-yl}methylene}-3-(3-pyridazinyl) -2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(4-cyclobutylaminobutyl)pyrrol-2-yl]methylene}-3-(3-pyridazinyl)-2- pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazoline-5 -ketone,

4-[(4-diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2-pyrazoline -5-keto,

4-{[3,5-Dimethyl-4-(2-ethylaminoethyl)-pyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2-pyrazoline- 5-keto,

4-{[3,5-Dimethyl-4-(2-phenylaminoethyl)pyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2-pyrazoline-5 -ketone,

4-{{3,5-Dimethyl-4-[2-(4-pyridylmethylamino)ethyl]pyrrol-2-yl}methylene}-3-(4-pyridazinyl)-2 -pyrazolin-5-one,

4-[(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazoline-5 -ketone,

4-{[4-(1-pyrrolidinylmethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2-pyrrole oxazolin-5-one,

4-{[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2-pyrazoline-5- ketone,

4-{{3-isopropyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-(4-pyridazinyl) -2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2- pyrazolin-5-one,

3-(4-pyridazinyl)-4-{{4-[3-(1-pyrrolidinyl)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene} -2-pyrazolin-5-one,

4-{[3-isopropyl-5-methyl-4-(4-piperidinobutyl)pyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2- pyrazolin-5-one,

4-{{4-[3-(4-pyridylmethylamino)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-3-(4-pyridazinyl )-2-pyrazolin-5-one,

4-{[4-(4-Dimethylaminobutyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2-pyrrole oxazolin-5-one,

4-[(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(4-pyridazinyl)-2-pyrazoline-5 -ketone,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidinyl)ethyl]pyrrol-2-yl}methylene}-3-(4-pyridazinyl) -2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-di(methoxyethyl)aminoethyl]-5-methylpyrrol-2-yl}methylene}-3-(4-pyridazine Base) -2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylaminopropyl)-5-methylpyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2-pyridine oxazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidinyl)propyl]-5-methylpyrrol-2-yl}methylene}-3 -(4-pyridazinyl)-2-pyrazolin-5-one,

4-([3-cyclopropyl-5-methyl-4-(3-phenylmethylaminopropyl)pyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2- pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidinyl)butyl]pyrrol-2-yl}methylene}-3-(4-pyridazinyl) -2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(4-cyclobutylaminobutyl)pyrrol-2-yl]methylene}-3-(4-pyridazinyl)-2- pyrazolin-5-one,

4-[(3,5-Dimethyl-4-(1-pyrrolidinylmethylpyrrol-2-yl)methylene]-3-(1,2,4-triazin-3-yl)- 2-pyrazolin-5-one,

4-[(4-Diethylaminomethyl-3,5-dimethylpyrrol-2-yl)methylene]-3-(1,2,4-triazin-3-yl)-2-pyrrole oxazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(1,2,4-triazin-3-yl )-2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-ethylaminoethyl)-pyrrol-2-yl]methylene}-3-(1,2,4-triazin-3-yl) -2-pyrazolin-5-one,

4-{[3,5-Dimethyl-4-(2-phenylaminoethyl)pyrrol-2-yl]methylene}-3-(1,2,4-triazin-3-yl)- 2-pyrazolin-5-one,

4-{{3,5-Dimethyl-4-[2-(4-pyridylmethylamino)ethyl]pyrrol-2-yl}methylene}-3-(1,2,4-triazine -3-yl)-2-pyrazolin-5-one,

4-{[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-(1,2,4-triazin-3-yl)-2 -pyrazolin-5-one,

4-[(4-Diethylaminomethyl-3-isopropyl-5-methylpyrrol-2-yl)methylene]-3-(1,2,4-triazin-3-yl)- 2-pyrazolin-5-one,

4-{[4-(1-pyrrolidinylmethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(1,2,4-triazine-3 -yl)-2-pyrazolin-5-one,

4-{{3-isopropyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-(1,2,4- Triazin-3-yl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(1,2,4-triazine- 3-yl)-2-pyrazolin-5-one,

4-{{4-[3-(1-pyrrolidinyl)propyl]-3-isopropyl-5-methylpyrrol-2-ylmethylene}-3-(1,2,4-tri Oxin-3-yl)-2-pyrazolin-5-one,

4-{[3-isopropyl-5-methyl-4-(4-piperidinobutyl)pyrrol-2-yl]methylene}-3-(1,2,4-triazine- 3-yl)-2-pyrazolin-5-one,

4-{{4-[3-(4-pyridylmethylamino)propyl]-3-isopropyl-5-methylpyrrol-2-yl}methylene}-3-(1,2,4 -Triazin-3-yl)-2-pyrazolin-5-one,

4-{[4-(4-Dimethylaminobutyl)-3-isopropyl-5-methylpyrrol-2-yl]methylene}-3-(1,2,4-triazine-3 -yl)-2-pyrazolin-5-one,

4-[(3-cyclopropyl-4-diethylaminomethyl-5-methylpyrrol-2-yl)methylene]-3-(1,2,4-triazin-3-yl)- 2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidinyl)ethyl]pyrrol-2-yl}methylene}-3-(1,2,4- Triazin-3-yl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-bis(methoxyethyl)aminoethyl]-5-methylpyrrol-2-yl}methylene}-3-(1,2, 4-triazin-3-yl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylaminopropyl)-5-methylpyrrol-2-yl]methylene}-3-(1,2,4-triazine-3 -yl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidinyl)propyl]-5-methylpyrrol-2-yl}methylene}-3 -(1,2,4-triazin-3-yl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenylmethylaminopropyl)pyrrol-2-yl]methylene}-3-(1,2,4-triazine- 3-yl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidinyl)butyl]pyrrol-2-yl}methylene}-3-(1,2,4- Triazin-3-yl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(4-cyclobutylaminobutyl)pyrrol-2-yl]methylene}-3-(1,2,4-triazine- 3-yl)-2-pyrazolin-5-one,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-trifluoromethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{{5-methyl-4-[2-(1-pyrrolidinylethyl)]-3-trifluoromethylpyrrol-2-yl}methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{[4-(2-Ethylaminoethyl)-5-methyl-3-trifluoromethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{5-methyl-4-[2-(4-pyridylmethylaminoethyl)]-3-trifluoromethylpyrrol-2-yl]methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-trifluoromethylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrrole oxazolin-5-one,

4-{[4-(2-aminoethyl)-5-methyl-3-trifluoromethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-tert-butylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{5-methyl-4-[2-(1-pyrrolidinylethyl)]-3-tert-butylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyr oxazolin-5-one,

4-{[4-(2-Ethylaminoethyl)-5-methyl-3-tert-butylpyrrol-2-yl]methylene)-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{5-methyl-4-[2-(4-pyridylmethylaminoethyl)]-3-tert-butylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-tert-butylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-aminoethyl)-5-methyl-3-tert-butylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{[4-(2-Diethylaminoethyl)-3-ethyl-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{3-Ethyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[3-Ethyl-4-(2-ethylaminoethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{{3-Ethyl-5-methyl-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-ethylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[4-(2-aminoethyl)-5-methyl-3-ethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclobutyl-4-(2-diethylaminoethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{3-cyclobutyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[3-cyclobutyl-4-(2-ethylaminoethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{3-cyclobutyl-5-methyl-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl]methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-cyclobutylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-aminoethyl)-5-methyl-3-cyclobutylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{[3-cyclopentyl-4-(2-diethylaminoethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{3-cyclopentyl-5-methyl-4-[2-(1-pyrrolidinylethyl)pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[3-cyclopentyl-4-(2-ethylaminoethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{3-cyclopentyl-5-methyl-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl]methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-cyclopentylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-aminoethyl)-5-methyl-3-cyclopentylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{[3-cyclohexyl-4-(2-diethylaminoethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{3-cyclohexyl-5-methyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[3-cyclohexyl-4-(2-ethylaminoethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{{3-cyclohexyl-5-methyl-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-cyclohexylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[4-(2-aminoethyl)-5-methyl-3-cyclohexylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-phenylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{5-methyl-3-phenyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-Ethylaminoethyl)-5-methyl-3-phenylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{{5-methyl-3-phenyl-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-phenylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[4-(2-aminoethyl)-5-methyl-3-phenylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-(4-methoxyphenyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazine Base-2-pyrazolin-5-one,

4-{[4-(2-ethylaminoethyl)-5-methyl-3-(4-methoxyphenyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyr oxazolin-5-one,

4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyr Azinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-(4-methoxyphenyl)pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{[4-(2-aminoethyl)-5-methyl-3-(4-methoxyphenyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-(2-pyridyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{{5-methyl-3-(2-pyridyl)-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl- 2-pyrazolin-5-one,

4-{[4-(2-Ethylaminoethyl)-5-methyl-3-(2-pyridyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{{5-methyl-3-(2-pyridyl)-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-(2-pyridyl)pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-aminoethyl)-5-methyl-3-(2-pyridyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-pyrazinylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{5-methyl-3-pyrazinyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-Ethylaminoethyl)-5-methyl-3-pyrazinylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{5-methyl-3-pyrazinyl-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-pyrazinylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-5-methyl-3-pyrazinylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-(2-imidazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{{5-methyl-3-(2-imidazolyl)-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl- 2-pyrazolin-5-one,

4-{[4-(2-Ethylaminoethyl)-5-methyl-3-(2-imidazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{{5-methyl-3-(2-imidazolyl)-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-(2-imidazolyl)pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-5-methyl-3-(2-imidazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-(2-pyrimidinyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[5-methyl-3-(2-pyrimidinyl)-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl- 2-pyrazolin-5-one,

4-{[4-(2-Ethylaminoethyl)-5-methyl-3-(2-pyrimidinyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{{5-methyl-3-(2-pyrimidinyl)-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-(2-pyrimidinyl)pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-5-methyl-3-(2-pyrimidinyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-(3-isoxazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazine Base-2-pyrazolin-5-one,

4-{[4-(2-ethylaminoethyl)-5-methyl-3-(3-isoxazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyr oxazolin-5-one,

4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyridine Azinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-(3-isoxazolyl)pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-5-methyl-3-(3-isoxazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-(2-furyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{{5-methyl-3-(2-furyl)-4-[2-(1-pyrrolidinylethyl)pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-Ethylaminoethyl)-5-methyl-3-(2-furyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{{5-methyl-3-(2-furyl)-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{4-[2-(1-imidazolyl)ethyl]-5-methyl-3-(2-furyl)pyrrol-2-yl}methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-5-methyl-3-(2-furyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-Diethylaminoethyl)-5-hydroxymethyl-3-isopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{{5-Hydroxymethyl-3-isopropyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{[4-(2-Ethylaminoethyl)-5-hydroxymethyl-3-isopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{5-Hydroxymethyl-3-isopropyl-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-5-hydroxymethyl-3-isopropylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-cyclopropylaminoethyl)-5-hydroxymethyl-3-isopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-[4-(2-Diethylaminoethyl)-3,5-dicyclopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-Dicyclopropyl-4-[2-(1-pyrrolidinylethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[4-(2-ethylaminoethyl)-3,5-dicyclopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-dicyclopropyl-4-[2-(4-pyridylmethylaminoethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{{4-[2-(1-imidazolyl)ethyl]-3,5-dicyclopropylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{[4-(2-cyclopropylaminoethyl)-3,5-dicyclopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{[4-(2-Diethylaminomethyl)-5-methyl-3-trifluoromethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{[4-(2-Dimethylaminomethyl)-5-methyl-3-trifluoromethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{{5-methyl-4-[2-(1-pyrrolidinylmethyl)]-3-trifluoromethylpyrrol-2-yl}methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{[4-(2-Ethylaminomethyl)-5-methyl-3-trifluoromethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{5-methyl-4-[2-(4-pyridylmethylaminomethyl)]-3-trifluoromethylpyrrol-2-yl]methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-trifluoromethylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrrole oxazolin-5-one,

4-{[4-(2-aminomethyl)-5-methyl-3-trifluoromethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{[4-(2-Diethylaminomethyl)-5-methyl-3-tert-butylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{[4-(2-Dimethylaminomethyl)-5-methyl-3-tert-butylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{5-methyl-4-[2-(1-pyrrolidinylmethyl)]-3-tert-butylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-Ethylaminomethyl)-5-methyl-3-tert-butylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{5-methyl-4-[2-(4-pyridylmethylaminomethyl)]-3-tert-butylpyrrol-2-yl}methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{4-[2-(1-imidazolyl)methyl]-5-methyl-3-tert-butylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[4-(2-aminomethyl)-5-methyl-3-tert-butylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{[4-(2-Diethylaminomethyl)-3-ethyl-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{[4-(2-Dimethylaminomethyl)-3-ethyl-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{3-Ethyl-5-methyl-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[3-Ethyl-4-(2-ethylaminomethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{{3-Ethyl-5-methyl-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-ethylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[4-(2-aminomethyl)-5-methyl-3-ethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclobutyl-4-(2-diethylaminomethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{[3-cyclobutyl-4-(2-dimethylaminomethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{3-cyclobutyl-5-methyl-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[3-cyclobutyl-4-(2-ethylaminomethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{3-cyclobutyl-5-methyl-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl]methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-cyclobutylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-aminomethyl)-5-methyl-3-cyclobutylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{[3-cyclopentyl-4-(2-diethylaminomethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{[3-cyclopentyl-4-(2-dimethylaminomethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{3-cyclopentyl-5-methyl-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[3-cyclopentyl-4-(2-ethylaminomethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{3-cyclopentyl-5-methyl-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl]methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-cyclopentylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-aminomethyl)-5-methyl-3-cyclopentylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{[3-cyclohexyl-4-(2-diethylaminomethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{[3-cyclohexyl-4-(2-dimethylaminomethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{3-cyclohexyl-5-methyl-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[3-cyclohexyl-4-(2-ethylaminomethyl)-5-methylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{{3-cyclohexyl-5-methyl-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-cyclohexylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[4-(2-aminomethyl)-5-methyl-3-cyclohexylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-Diethylaminomethyl)-5-methyl-3-phenylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{[4-(2-Dimethylaminomethyl)-5-methyl-3-phenylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{5-methyl-3-phenyl-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-Ethylaminomethyl)-5-methyl-3-phenylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{{5-methyl-3-phenyl-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-phenylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[4-(2-aminomethyl)-5-methyl-3-phenylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-Diethylaminomethyl)-5-methyl-3-(4-methoxyphenyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{[4-(2-Dimethylaminomethyl)-5-methyl-3-(4-methoxyphenyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazine Base-2-pyrazolin-5-one,

4-{[4-(2-ethylaminomethyl)-5-methyl-3-(4-methoxyphenyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyr oxazolin-5-one,

4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyridine Azinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-(4-methoxyphenyl)pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{[4-(2-aminomethyl)-5-methyl-3-(4-methoxyphenyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-Diethylaminomethyl)-5-methyl-3-(2-pyridyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-Dimethylaminomethyl)-5-methyl-3-(2-pyridyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{{5-methyl-3-(2-pyridyl)-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl- 2-pyrazolin-5-one,

4-{[4-(2-Ethylaminomethyl)-5-methyl-3-(2-pyridyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{{5-methyl-3-(2-pyridyl)-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-(2-pyridyl)pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-aminomethyl)-5-methyl-3-(2-pyridyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{[4-(2-Diethylaminomethyl)-5-methyl-3-pyrazinylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{[4-(2-Dimethylaminomethyl)-5-methyl-3-pyrazinylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{5-methyl-3-pyrazinyl-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-Ethylaminomethyl)-5-methyl-3-pyrazinylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5- ketone,

4-{{5-methyl-3-pyrazinyl-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-pyrazinylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-cyclopropylaminomethyl)-5-methyl-3-pyrazinylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{[4-(2-Diethylaminomethyl)-5-methyl-3-(2-imidazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-Dimethylaminomethyl)-5-methyl-3-(2-imidazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{{5-methyl-3-(2-imidazolyl)-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl- 2-pyrazolin-5-one,

4-{[4-(2-Ethylaminomethyl)-5-methyl-3-(2-imidazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{{5-methyl-3-(2-imidazolyl)-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-(2-imidazolyl)pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-cyclopropylaminomethyl)-5-methyl-3-(2-imidazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-Diethylaminomethyl)-5-methyl-3-(2-pyrimidinyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-Dimethylaminomethyl)-5-methyl-3-(2-pyrimidinyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{5-methyl-3-(2-pyrimidinyl)-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-Ethylaminomethyl)-5-methyl-3-(2-pyrimidinyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{{5-methyl-3-(2-pyrimidinyl)-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl}methyl]-5-methyl-3-(2-pyrimidinyl)pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-cyclopropylaminomethyl)-5-methyl-3-(2-pyrimidinyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-Diethylaminoethyl)-5-methyl-3-(3-isoxazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{[4-(2-Dimethylaminoethyl)-5-methyl-3-(3-isoxazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazine Base-2-pyrazolin-5-one,

4-{[4-(2-Ethylaminomethyl)-5-methyl-3-(3-isoxazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyridine Azinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-(3-isoxazolyl)pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{[4-(2-cyclopropylaminomethyl)-5-methyl-3-(3-isoxazolyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-Diethylaminomethyl)-5-methyl-3-(2-furyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[4-(2-Dimethylaminomethyl)-5-methyl-3-(2-furyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{{5-methyl-3-(2-furyl)-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl- 2-pyrazolin-5-one,

4-{[4-(2-Ethylaminomethyl)-5-methyl-3-(2-furyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{{5-methyl-3-(2-furyl)-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl -2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-methyl-3-(2-furyl)pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{[4-(2-cyclopropylaminomethyl)-5-methyl-3-(2-furyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyridine oxazolin-5-one,

4-{[4-(2-Diethylaminomethyl)-5-hydroxymethyl-3-isopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{[4-(2-Dimethylaminomethyl)-5-hydroxymethyl-3-isopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{{5-Hydroxymethyl-3-isopropyl-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2- pyrazolin-5-one,

4-{[4-(2-Ethylaminomethyl)-5-hydroxymethyl-3-isopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone,

4-{{5-Hydroxymethyl-3-isopropyl-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2 -pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-5-hydroxymethyl-3-isopropylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrrole oxazolin-5-one,

4-{[4-(2-cyclopropylaminomethyl)-5-hydroxymethyl-3-isopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[4-(2-Diethylaminomethyl)-3,5-dicyclopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{[4-(2-Dimethylaminomethyl)-3,5-dicyclopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one ,

4-{{3,5-Dicyclopropyl-4-[2-(1-pyrrolidinylmethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline -5-keto,

4-{[4-(2-ethylaminomethyl)-3,5-dicyclopropylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-Dicyclopropyl-4-[2-(4-pyridylmethylaminomethyl)]pyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{{4-[2-(1-imidazolyl)methyl]-3,5-dicyclopropylpyrrol-2-yl}methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-[(4-cyclopropylaminomethyl-3,5-dicyclopropylpyrrol-2-yl)methylene]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopropylaminomethyl-5-methyl-4-(2-diethylaminoethyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazole Lin-5-one,

4-{[3-cyclopropylaminomethyl-5-methyl-4-(2-hydroxyethyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto,

4-{[3-Dimethylaminomethyl-5-methyl-4-(2-diethylaminoethyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline -5-keto, and

4-{[3-Hydroxymethyl-5-methyl-4-(2-diethylaminoethyl)pyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline-5 -ketone.

Compounds of formula I may exist as salts with pharmaceutically acceptable acids. The present invention includes such salts. Examples of such salts include hydrochloride, hydrobromide, sulfate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, tartrate [e.g. (+) - tartrates, (-)-tartrates or mixtures thereof, including racemic mixtures], succinates, benzoates and salts with amino acids such as glutamic acid. These salts can be prepared according to methods known to those skilled in the art.

Certain compounds of formula I having acidic substituents may exist as their salts with pharmaceutically acceptable bases. The present invention includes these salts. Examples of such salts include sodium salts, potassium salts, lysine salts and arginine salts. These salts can be prepared according to methods known to those skilled in the art.

Certain compounds of formula I and salts thereof may exist in more than one crystalline form, and the invention includes each crystalline form and mixtures thereof.

Certain compounds of formula I and their salts may also exist in the form of solvates, such as hydrates, and the present invention includes each solvate and mixtures thereof.

Certain compounds of formula I may contain one or more chiral centers and exist in different optically active forms. When a compound of formula I contains one chiral center, the compound exists as two enantiomers, and the present invention includes both enantiomers and mixtures thereof. The two enantiomers can be resolved by methods known to those skilled in the art, for example by forming separable diastereomeric salts, such as by crystallization; formation of separable diastereomeric derivatives or complexes, e.g. by crystallization, gas-liquid or liquid chromatography; selective reaction of one enantiomer with an enantiomer-specific reagent, e.g. enzymatic esterification; or gaseous - Liquid or liquid chromatography, for example on a chiral support, such as silica gel bound to a chiral ligand, or in the presence of a chiral solvent. Clearly, if the desired enantiomer is converted to another chemical entity by one of the separation methods described above, the next step must be to liberate the desired enantiomeric form. Alternatively, specific enantiomers may be synthesized by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents, or by converting one enantiomer into the other by asymmetric transformation.

When a compound of formula I contains more than one chiral center, it may exist in diastereoisomeric forms. The diastereoisomeric pairs may be separated according to methods known to those skilled in the art, such as chromatography or crystallization, and the individual enantiomers of each pair may be separated as described above. The present invention includes each diastereoisomer of the compound of formula I and mixtures thereof.

Certain compounds of formula I may exist in different tautomeric forms or in different geometric isomeric forms, and the present invention includes each tautomer and/or geometric isomer of the compounds of formula I and mixtures thereof.

Certain compounds of formula I may exist in different separable stable conformational forms. Torsional asymmetry is due to restricted rotation around an asymmetric single bond, for example due to steric hindrance or ring strain, which allows the separation of different conformers. The present invention includes each conformational isomer of the compound of formula I and mixtures thereof.

Certain compounds of formula I may exist in zwitterionic form, and the present invention includes each zwitterionic form of compounds of formula I and mixtures thereof.

The compounds of the invention are suitable as inhibitors of serine/threonine and tyrosine kinases. In particular, the compounds of the invention are suitable as inhibitors of tyrosine kinases which are important in hyperproliferative diseases, especially in the process of angiogenesis. For example, some of these compounds are inhibitors of receptor kinases such as KDR, Flt-1, FGFR, PDGFR, c-Met or IGF-1-R. Since these compounds are anti-angiogenic agents, they are important substances for inhibiting progressive diseases in which angiogenesis is an important component. Certain compounds of the invention are potent inhibitors of serine/threonine kinases such as erk, MAP kinase, cdks, Plk-1 or Raf-1. These compounds are useful in the treatment of cancer and hyperproliferative diseases. In addition, certain compounds are potent inhibitors of non-receptor kinases such as src, lyn, lck, fyn, blk, hck. These compounds are useful in the treatment of cancer, hyperproliferative diseases and immune diseases.

The present invention provides methods of inhibiting the activity of tyrosine kinases and serine/threonine kinases comprising administering to said kinases a compound of formula I at a concentration sufficient to inhibit the activity of said kinases.

The present invention also includes the application of these compounds in a pharmaceutical composition containing a pharmaceutically effective amount of the above compound and a pharmaceutically acceptable carrier or excipient. These pharmaceutical compositions can be administered to an individual to slow or stop the angiogenic process in angiogenesis-assisted diseases, or to treat edema, leakage, exudate or ascites and other diseases associated with vascular hyperpermeability. Certain pharmaceutical compositions can be administered to individuals to treat cancer and hyperproliferative diseases by inhibiting serine/threonine kinases such as cdk, Plk-1, erk, and the like.

Detailed description of the invention

The compounds of the invention possess anti-angiogenic properties. These anti-angiogenic properties result from at least partial inhibition of protein tyrosine kinases essential for the angiogenic process. These compounds can therefore be used as active drugs against diseases such as arthritis, atherosclerosis, psoriasis, hemangiomas, myocardial angiogenesis, coronary and lateral processes, ischemic extremity angiogenesis, Wound healing, peptic ulcer, diseases associated with Helicobacter, angiogenic diseases caused by viruses, bone fractures, Crow-Fukase syndrome (POEMS), preeclampsia, menorrhagia, fever from cat scratches, flushing, new Vascular glaucoma and retinopathy such as those associated with diabetic retinopathy, retinopathy of prematurity, or age-related macular degeneration. In addition, some of these compounds are useful against solid tumors, malignant ascites, hematopoietic cancers and hyperproliferative diseases such as thyroid hyperplasia (especially Graves' disease) and cysts (such as polycystic ovary syndrome characterized by ovarian stroma). Syndrome (Stiller Syndrome)) because these diseases require the proliferation of vascular cells for their growth and/or metastasis.

Furthermore, certain compounds can be used as active drugs in the treatment of burns, chronic lung disease, stroke, polyps, allergies, chronic and allergic inflammation, delayed-type allergy, ovarian hyperstimulation syndrome, associated with brain tumors Cerebral edema, high-altitude, cerebral or pulmonary edema due to trauma or hypoxia, ocular and macular edema, ascites, and other disorders in which vascular hyperpermeability, leakage, exudate, protein extravasation, or edema are manifestations disease. These compounds are also useful in the treatment of diseases in which protein extravasation leads to deposition of fibrin and extracellular matrix, promoting matrix proliferation (eg keloids, fibrosis, cirrhosis and gastric canal syndrome). Increased VEGF production leads to enhanced inflammatory processes, such as monocyte recruitment and activation. The compounds of the invention are also useful in the treatment of inflammatory diseases such as inflammatory bowel disease (IBD) and Crohn's disease.

VEGF are unique in that they are the only angiogenic growth factors known to cause vascular hyperpermeability and edema formation. Indeed, the appearance of vascular hyperpermeability and edema associated with the expression and administration of many other growth factors is mediated by VEGF production. Inflammatory cytokines stimulate VEGF production. Hypoxia results in a marked upregulation of VEGF in a variety of tissues, thus situations associated with infarction, occlusion, ischemia, anemia or decreased circulation often elicit VEGF/VPF mediated responses. Vascular hyperpermeability, combined with edema, altered transendothelial exchange, and macromolecular extravasation (often accompanied by extravasation of blood cells) can lead to excessive deposition of matrix, abnormal interstitial proliferation, fibrosis, etc. Thus, VEGF-mediated hyperpermeability has an important contribution to disorders with these etiological features.

It should be appreciated that the diseases listed above are mediated to a significant extent by protein tyrosine kinase activity involving KDR/VEGFR-2 and/or Flt-1/VEGFR-1 tyrosine kinases. By inhibiting the activity of these tyrosine kinases, the progression of the aforementioned diseases is inhibited because the angiogenic or vascular hyperpermeable components of the disease state are strictly curtailed. The action of certain compounds of the invention, through their selectivity for specific tyrosine kinases, minimizes the side effects that occur with less selective tyrosine kinase inhibitors. Certain compounds of the invention are also potent inhibitors of FGFR, PDGFR, c-Met and IGF-1-R. These receptor kinases can directly or indirectly potentiate angiogenic and hyperproliferative responses in various diseases so that their inhibition can prevent disease progression.

The compounds of the present invention have inhibitory activity against protein kinases. That is, these compounds modulate signaling through protein kinases. The compounds of the present invention inhibit protein kinases of the serine/threonine and tyrosine kinase classes. In particular, these compounds selectively inhibit KDR/FLK-1/VEGFR-2 tyrosine kinase activity. Certain compounds of the present invention also inhibit the activity of other tyrosine kinases such as Flt-1/VEGFR-1, FGFR, PDGFR, IGF-1R, c-Met, Src-subfamily kinases such as Lck, Src, fyn, yes, etc. . In addition, certain compounds of the present invention significantly inhibit serine/threonine kinases such as PKC, MAP kinase, erk, CDKs, Plk-1 or Raf-1 that play an important role in cell proliferation and cell cycle progression. The potency and specificity of the compounds of the general formula of the present invention against specific protein kinases can usually be changed by changing the nature, number and arrangement of the substituents (ie R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ and R ₇ ) and Change or optimization due to conformational constraints. In addition, metabolites of certain compounds also possess significant protein kinase inhibitory activity.

When administered to individuals in need thereof, the compounds of the invention inhibit vascular hyperpermeability and edema formation in these individuals. These compounds are believed to act by inhibiting the activity of the KDR tyrosine kinase involved in the process of vascular hyperpermeability and edema formation. KDR tyrosine kinase is also known as FLK-1 tyrosine kinase, NYK tyrosine kinase or VEGFR-2 tyrosine kinase. When vascular endothelial growth factor (VEGF) or another activating ligand (such as VEGF-C, VEGF-D, VEGF-E, or HIV Tat protein) binds to the KDR tyrosine kinase receptor on the surface of vascular endothelial cells , KDR tyrosine kinase is activated. After activation of this KDR tyrosine kinase, vascular hyperpermeability occurs and fluid passes from the blood through the vessel wall into the interstitial cavity, thereby forming an edematous area. Exudation of blood cells is also often accompanied by this reaction. Similarly, excessive vascular hyperpermeability can disrupt normal molecular exchange across the endothelium in at-risk tissues and organs (eg, lung and kidney), causing extravasation and deposition of macromolecules. Following an acute response to KDR stimulation, which is believed to promote the subsequent angiogenic process, prolonged KDR tyrosine kinase stimulation results in proliferation and chemotaxis of vascular endothelial cells and neovascularization. By inhibiting KDR tyrosine kinase activity, or by blocking the production of activating ligands, by blocking the binding of activating ligands to KDR tyrosine kinase receptors, by preventing receptor dimerization and phosphate transfer, by inhibiting KDR tyrosine kinase amino acid kinase activity (inhibition of the phosphorylation function of the enzyme) or by some other mechanism that blocks its downstream signaling (D. Mukhopedhyay et al., Cancer Res. 58: 1278-1284 (1998), which is incorporated herein by reference ), hyperosmolarity and associated extravasation, subsequent edema formation and matrix deposition, and angiogenic responses can be inhibited or minimized.

A preferred group of compounds of the invention have the ability to inhibit KDR tyrosine kinase activity without significantly inhibiting Flt-1 tyrosine kinase activity (Flt-1 tyrosine kinase is also known as VEGFR-1 tyrosine kinase). KDR tyrosine kinase and Flt-1 tyrosine kinase are activated by VEGF binding to KDR tyrosine kinase receptor and Flt-1 tyrosine kinase receptor, respectively. Since Flt-1 tyrosine kinase activity can mediate important consequences in endothelial maintenance and vascular function, inhibition of this enzyme activity can lead to toxic or adverse effects. At least this inhibition is unnecessary to block the angiogenic response, induce vascular hyperpermeability and edema formation, and thus be uneconomical and of no value to the individual. Certain preferred compounds of the invention are unique in that they inhibit the activity of VEGF-receptor tyrosine kinase (KDR) activated by activating ligands, while not inhibiting other receptor tyrosine kinases that are also activated by certain activating ligands Acid kinases, such as Flt-1. Accordingly, preferred compounds of the invention are selective in their tyrosine kinase inhibitory activity.

The compounds of the present invention are also useful in the treatment of ulcers - bacterial, fungal, Moran's ulcer and ulcerative colitis.

The compounds of the invention are also suitable for the treatment of diseases in which undesired angiogenesis, edema or interstitial deposition occur in viral infections, such as herpes simplex, herpes zoster, AIDS, parapoxvirus, psoriasis, Kaposi's sarcoma, protozoa Infections and toxoplasmosis, endometriosis, ovarian hyperstimulation syndrome, preeclampsia, menorrhagia, systemic lupus erythematosus, sarcoidosis, synovitis, inflammatory bowel disease, Crohn's disease , sickle cell anemia, Lyme disease, pemphigoid, Paget's disease, hyperviscosity syndrome, Osler-Weber-Rendu disease, chronic inflammation, chronic closed lung disease, asthma, rheumatoid arthritis and osteoarthritis, and edema after burns, trauma, radiation, or stroke.

In addition to retinopathy and macular degeneration, the compounds of the present invention are also useful in the treatment of eye diseases such as ocular and macular edema, ocular neovascular disease, scleritis, radial keratotomy, uveitis, vitreitis, myopia, sunken eyes, Chronic retinal detachment, laser postoperative complications, conjunctivitis, xanthomatosis and Earl's disease.

The compounds of the invention are also useful in the treatment of cardiovascular diseases such as atherosclerosis, restenosis, vascular occlusion and carotid occlusive disease.

The compounds of the invention are also useful in the treatment of cancer-related indications such as solid tumors, sarcomas (especially Ewing's sarcoma and osteosarcoma), retinoblastoma, rhabdomyosarcoma, neuroblastoma, hematopoietic malignancies including leukemia and lymphoid Tumors, pleural or pericardial effusions caused by tumors, and malignant ascites.

The compounds of the invention are also useful in the treatment of Crow-Fukase (POEMS) syndrome and diabetic diseases such as glaucoma, diabetic retinopathy and microangiopathy.

It should be appreciated that the diseases listed above are mediated to a significant extent by the activity of protein tyrosine kinases involving VEGF receptors such as KDR and Flt-1. By inhibiting the activity of these receptor tyrosine kinases, the progression of the aforementioned diseases is inhibited because the angiogenic component of the disease state is strictly curtailed. The action of the compounds of the invention, through their selectivity for specific tyrosine kinases, minimizes the side effects that occur with less selective tyrosine kinase inhibitors.

In another aspect, the present invention provides compounds of the formula I defined at the outset above (including the accompanying condition). In a further aspect, the present invention provides the use of a compound of formula I defined at the outset above (including provisos) for the manufacture of a medicament for inhibiting protein kinase activity.

In the present invention, the following definitions are used:

"Physiologically acceptable salts" refer to those that retain the biological potency and properties of the free base, and are obtained by mixing with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid or organic acids such as sulfonic acid, carboxylic acid, organic phosphoric acid. , methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, lactic acid and tartaric acid, etc.

"Alkyl" means a saturated aliphatic hydrocarbon, including straight and branched chain groups having 1-6 carbon atoms or cyclic hydrocarbons having 3-6 carbon atoms.

"Alkoxy" means "O-alkyl", wherein "alkyl" is as defined above.

pharmaceutical preparations

The compound of the present invention can be administered to human patients by itself or in a pharmaceutical composition in which the compound is combined with a suitable carrier or excipient to treat or improve vascular hyperpermeability, edema and related diseases. mix. Mixtures of these compounds may also be administered to the patient as a pure mixture or in suitable formulated pharmaceutical compositions. A therapeutically effective dose further refers to an amount of compound sufficient to prevent or attenuate inappropriate neovascularization, hyperproliferative disease progression, edema, VEGF-related hyperosmolarity and/or VEGF-related hypotension. Techniques for formulating and administering the compounds of the present application can be found in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA, most recent edition.

Route of administration

Suitable routes of administration may, for example, include oral, eye drops, rectal, transmucosal, topical or enteral administration; parenteral administration includes intramuscular, subcutaneous, intramedullary injection and intrathecal, intraventricular direct injection, intravenous Intraperitoneal, intranasal or intraocular injection.

Alternatively, the compound may be administered locally rather than systemically, for example by injecting the compound directly into the site of edema, usually in a depot or sustained release formulation.

Furthermore, the drug can be administered in a targeted drug delivery system, such as liposomes coated with endothelial cell-specific antibodies.

Composition/Preparation

The pharmaceutical compositions according to the invention can be prepared in a manner known per se, for example by conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes.

Therefore, the pharmaceutical compositions used in the present invention can be formulated in a conventional manner using one or more physiologically acceptable carriers, which include excipients and auxiliaries to facilitate processing of the active compounds into pharmaceutically acceptable preparations . Proper formulation is dependent on the route of administration chosen.

For injection, the medicaments of the invention can be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks' solution, Ringer's solution or physiological saline buffer. For transmucosal administration, penetrants appropriate to the permeation barrier are used in the formulation. Such penetrants are generally known in the art.

For oral administration, the compounds can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art. For oral ingestion by a patient to be treated, such carriers enable the compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like. Pharmaceutical preparations for oral administration can be obtained by mixing the active compound with a solid excipient, optionally grinding a resulting mixture, and granulating the mixture, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are especially fillers such as sugars including lactose, sucrose, mannitol or sorbitol; cellulose preparations such as corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth, methylcellulose, hydroxy Propyl methylcellulose, sodium carboxymethylcellulose, and/and polyvinylpyrrolidone (PVP). If desired, disintegrants such as cross-linked polyvinylpyrrolidone, agar or alginic acid or a salt thereof such as sodium alginate may be added.

Dragee cores are coated with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinylpyrrolidone, carbopol gum, polyethylene glycol and/or titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixture. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different doses of combined active compound.

Pharmaceutical preparations which can be administered orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers can be added. All oral formulations should be in dosages suitable for the form of administration.

For buccal administration the composition may be in the form of tablets or lozenges formulated in conventional manner.

For administration by inhalation, the compounds for use in the present invention are usually administered in the form of an aerosol spray from pressurized packs or nebulizers using suitable propellants such as dichlorodifluoromethane, trichlorofluoromethane, dichlorofluoromethane, Chlorotetrafluoroethane, carbon dioxide or other suitable gas. For pressurized aerosols, the dosage unit may be fitted with a valve to determine the metered release. Capsules and cartridges of eg gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch. The compounds may be formulated for parenteral administration in the form of injections, such as concentrated bolus injections or continuous infusions. Formulations for injection may be presented in unit dosage form such as ampoules or in multi-dose containers, with a preservative. The compositions may be suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.

Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Additionally, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the stability of the compounds to allow for the preparation of highly concentrated solutions.

Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, eg sterile pyrogen-free water, before use.

The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, eg, containing conventional suppository bases such as cocoa butter or other glycerides.

In addition to the formulations described above, the compound may also be formulated as a depot formulation. The long-acting formulations may be administered by implantation (eg, subcutaneous or intramuscular implantation or administration by intramuscular injection). Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials or ion exchange resins (eg, as emulsions in acceptable oils), or as poorly soluble derivatives such as poorly soluble salts.

An example of a pharmaceutically acceptable carrier for a hydrophobic compound of the invention is a co-solvent system comprising benzyl alcohol, a non-polar surfactant, a water-miscible organic polymer, and an aqueous phase. The co-solvent system may be a VPD co-solvent system. VPD is a solution of 3% w/v benzyl alcohol, 8% w/v non-polar surfactant Tween 80 and 65% w/v polyethylene glycol 300 in absolute ethanol to the required volume. The VPD co-solvent system (VPD: 5W) consisted of VPD diluted 1:1 with 5% dextrose in water. The co-solvent system completely dissolves hydrophobic compounds and itself produces low toxicity upon systemic administration. Of course, the proportions of the co-solvent system can be varied considerably so long as the solubility and toxicity properties are not compromised. In addition, the properties of the co-solvent components can be changed: for example, other less toxic, non-polar surfactants can be used instead of Tween 80; the portion size of polyethylene glycol can be changed; other biocompatible polymers can be substituted polyethylene glycols, such as polyvinylpyrrolidone; and other sugars or polysaccharides may be substituted for glucose.

Alternatively, other delivery systems for hydrophobic pharmaceutical compounds can be used. Liposomes and emulsions are well known hydrophobic drug delivery vehicles and carriers. Certain organic solvents such as dimethylsulfoxide can also be used, although their toxicity cost is usually greater. Additionally, the compounds can be administered using a sustained-release system, such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent. Various sustained release materials have been established and are well known to those skilled in the art. Sustained-release capsules release the compound for several weeks to as long as 100 days, depending on their chemical nature. Depending on the chemical nature and biological stability of the therapeutic agent, other strategies for protein stabilization may be used.

The pharmaceutical composition may also contain suitable solid or gel phase carriers or excipients. Examples of such carriers or excipients include, but are not limited to, calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin and polymers such as polyethylene glycol.

Many of the organic molecular compounds of the invention can be used in the form of their salts with pharmaceutically compatible counterions. Pharmaceutically compatible salts can be formed with many acids including, but not limited to, hydrochloric, sulfuric, acetic, lactic, tartaric, malic, succinic, and the like. Salts are more soluble in water or other protic solvents than the corresponding free bases.

effective dose

Pharmaceutical compositions suitable for use in the present invention include compositions wherein the active ingredient is contained in an effective amount to achieve its intended purpose. In particular, a therapeutically effective amount means an amount effective to prevent the development of existing symptoms or to alleviate existing symptoms in the subject being treated. Determination of an effective amount is within the capability of those skilled in the art.

For many of the compounds used in the methods of the invention, the therapeutically effective amount can be estimated first from cellular assays. For example, a dose can be formulated in cellular and animal models to achieve a range of circulating concentrations that include _IC50 values (ie, the concentration of test compound that achieves a half-maximal inhibition of the activity of a indicated protein kinase) determined in cellular assays. In some cases, determination of _IC50 values in the presence of 3-5% serum albumin is appropriate because this determination approximates the binding of plasma proteins to the compound. Such information can be used to more accurately determine effective doses in humans. In addition, most preferably systemically administered compounds that achieve safe levels in plasma effectively inhibit protein kinase signaling in intact cells.

A therapeutically effective dose is that amount of a compound that results in amelioration of symptoms in a patient. Toxicity and therapeutic efficacy of the compounds can be determined by standard pharmaceutical methods in cell cultures or experimental animals, eg, determination of the maximum tolerated dose (MTD) and _ED50 values (the effective dose at 50% of the maximum response). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio between MTD and _ED50 . Compounds with high therapeutic indices are preferred. The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for human use. Such doses of the compounds lie preferably within a range of circulating concentrations that include the _ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration. The precise formulation, administration volume and dosage can be selected by the physician according to the patient's condition. (See eg Fingl et al., 1975, "The Pharmacological Basis of Therapeutics", Ch. 1 pl). In crisis management, MTDs may be needed in acute bolus form or by infusion to achieve a rapid response.

Dosage and time intervals may be adjusted individually so that plasma levels of the active substance are sufficient to maintain the kinase modulating effect or minimum effective concentration (MEC). The MEC will vary for each compound, but can be estimated from in vitro data; for example, the concentration required to achieve 50-90% inhibition of a protein kinase is estimated using the assay described above. Dosages required to achieve the MEC will depend on individual characteristics and route of administration. However, plasma concentrations can be determined using HPLC analysis or bioassays.

Dosing intervals can also be determined using MEC values. Compounds should be administered using a dosing regimen that maintains plasma levels above the MEC for 10-90% of the time, preferably 30-90%, most preferably 50-90% of the time until the desired amelioration of symptoms is achieved. If administered locally or selectively uptake, the local effective concentration of the drug may not be related to the plasma concentration.

The amount of the composition administered will, of course, depend on the subject being treated, the patient's weight, the severity of the affliction, the mode of administration, and the judgment of the prescribing physician.

Package

The compositions may, if desired, be presented in a pack or dispenser device containing one or more unit dosage forms containing the active ingredient. The pack may eg comprise metal or plastic foil, eg a blister pack. The pack or dispenser device may be accompanied by instructions for use. Compositions containing a compound of the invention formulated in a compatible pharmaceutically acceptable carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.

In certain formulations it may be advantageous to use the compounds of the invention in the form of very small particles, for example obtained by liquid energy milling.

The use of the compounds of the invention for the preparation of pharmaceutical compositions is illustrated by the following description. In this description, the term "active compound" refers to any compound of the present invention, but especially to the end product compound of any preceding Example.

a) Capsules

In the preparation of capsules, 10 parts by weight of active compound can be depolymerized and mixed with 240 parts by weight of lactose. The mixture is filled into hard gelatin capsules, each capsule containing a unit dose or part of a unit dose of active compound.

b) tablet

Tablets can be prepared from the following ingredients.

parts by weight

active compound 10

Lactose 190

cornstarch 22

Polyvinylpyrrolidone 10

Magnesium stearate 3

The active compound, lactose and some starch are depolymerized, mixed and the resulting mixture is granulated with polyvinylpyrrolidone in ethanol. The dry granules are mixed with the magnesium stearate and the remaining starch. The mixture is then compressed in a tablet machine to yield tablets, each tablet containing a unit dose or part of a unit dose of active compound.

c) Enteric-coated tablets

Tablets can be prepared according to the method of (b) above. Tablets may be enteric coated according to conventional methods using a solution of 20% cellulose acetate phthalate and 3% diethyl phthalate in ethanol:dichloromethane (1:1).

d) suppositories

In preparing suppositories, 100 parts by weight of the active compound can be incorporated into 1300 parts by weight of a triglyceride suppository base, and the mixture is formed into suppositories, each suppository containing a therapeutically effective amount of the active ingredient.

In the compositions of the invention, the active compounds may, if desired, be combined with other compatible pharmacologically active ingredients. For example, compounds of the invention may be administered in combination with one or more additional pharmaceutically active substances that inhibit or prevent VEGF production, attenuate intracellular responses to VEGF, block intracellular signaling, inhibit vascular permeability hyperactivity, reduce inflammation, or inhibit or prevent edema formation or neovascularization. The compound of the invention may be administered before, after or simultaneously with the additional pharmaceutically active substance, whichever course of administration is appropriate. Additional pharmaceutical actives include, but are not limited to, anti-edematous steroids, NSAIDS, ras inhibitors, anti-TNF agents, anti-IL-1 agents, antihistamines, PAF-antagonists, COX-1 inhibitors, COX-2 inhibitors agents, NO synthase inhibitors, PKC inhibitors and PI3 kinase inhibitors. The compounds of the invention act additively or synergistically with additional pharmaceutically active substances. Thus, administration of substances that inhibit angiogenesis, vascular hyperpermeability and/or formation of edema in combination can significantly reduce the effects of hyperproliferative disease, angiogenesis, vascular hyperpermeability or edema compared to administration of each substance alone. Harmful effect. In the treatment of malignant diseases, it is contemplated that it may be combined with antiproliferative or cytotoxic chemotherapy.

The present invention also includes the use of compounds of formula I as medicaments.

Src and Syk family kinases play key roles in regulating immune function. The Src family currently includes Fyn, Lck, Fgr, Fes, Lyn, Src, Yes, Hck, and Blk. It should now be understood that the Syk family includes only Zap and Syk. Janus family kinases are involved in the transmission of growth factor and proinflammatory cytokine signaling through a number of receptors. Although members of the Tec family of kinases, BTK and ITK, play little-understood roles in immunobiology, their modulation with inhibitors has proven therapeutically beneficial. The kinases RIP, IRAK-1, IRAK-2, NIK, TPL-2/COT, IKK-1 and IKK-2 are involved in the key proinflammatory cytokine TNF and IL-1 signaling pathways. Since the compounds of formula I are capable of inhibiting one or more of these kinases, they are useful as immunomodulators for maintenance of allografts and treatment of autoimmune diseases. Through their ability to modulate T cell activity or potentiate inflammatory processes, these compounds are useful in the treatment of this autoimmune disease. Due to the phenomenon of rejection, either host-to-solid-organ graft rejection, or bone-marrow graft-to-host rejection, grafts are currently limited by the toxicity of immunosuppressive agents and would benefit from effective drugs with improved therapeutic indices. Gene targeting experiments have demonstrated that Src plays an important role in the biology of osteoclasts responsible for bone resorption. Through their ability to regulate Src, the compounds of formula I are also useful in the treatment of osteoporosis, osteopetrosis, Paget's disease, tumor-induced hypercalcemia and in the treatment of bone metastases.

Many protein kinases have been shown to be proto-oncogenes. Chromosomal breaks (ltk kinase breakpoint on chromosome 5), translocations such as the Abl gene with BCR (Philadelphia chromosome), truncations such as c-Kit or EGFR, or mutations (such as Met) leading to unregulated protein production, which is caused by proto-oncogenic Gene conversion into oncogene products. In other tumors, neoplasia is driven by autocrine or paracrine ligand/growth factor receptor interactions. Many src-family kinases are often associated with downstream signaling, thus enhancing neoplasia, and can themselves become oncogenes through overexpression or mutation. By inhibiting the protein kinase activity of these proteins, the disease process can be interrupted. Vascular restenosis may involve smooth muscle and endothelial cell proliferation promoted by FGF and/or PDGF. Ligand stimulation of FGFR, PDGFR, IGF1-R and c-Met in vivo is pro-angiogenic and potentiates angiogenesis-dependent diseases. Inhibition of FGFr, PDGFr, c-Met or IGF1-R kinase activity may be an effective strategy to inhibit these phenomena. Thus, inhibition of normal or abnormal c-kit, c-met, c-fms, src-family members, EGFr, erbB2, erbB4, BCR-Ab1, PDGFr, FGFr, IGF1-R and other receptor or cytoplasmic tyrosine Kinases are valuable in the treatment of benign and neoplastic proliferative diseases.

In many pathological conditions (eg, solid primary tumors and metastases, Kaposi's sarcoma, rheumatoid arthritis, visual loss due to inappropriate ocular neovascularization, psoriasis, and atherosclerosis), once persistent Angiogenesis, the progression of the disease is accidental. Polypeptide growth factors and their corresponding endothelial cell-specific receptor tyrosine kinases (such as KDR/VEGFR-2, Flt1/VEGFR-1, Tie-2/Tek, and Tie ) is important for stimulating endothelial cell growth, migration, organization, differentiation and establishment of the necessary new functional vasculature. The activity of VEGF "vascular permeability factor" in mediating vascular hyperpermeability, VEGF stimulation of VEGFR kinases is believed to play an important role in the following conditions: neoplastic ascites formation, brain and pulmonary edema, pleural and pericardial leaks Effusion, delayed-type hypersensitivity reaction, tissue edema and organ dysfunction after trauma, burns, ischemia, diabetic complications, endometriosis, adult respiratory distress syndrome (ARDS), post-cardiopulmonary bypass-related hypotension and hyperosmolarity, as well as glaucoma due to ocular edema or loss of vision due to inappropriate neovascularization. In addition to VEGF, the recently identified VEGF-C and VEGF-D as well as virally encoded VEGF-E or HIV-Tat proteins can also induce vascular hyperpermeability responses by stimulating VEGFR kinase. Tie-2 is also expressed in selected populations of hematopoietic stem cells, where Tie-2 plays an important role in their recruitment, adhesion, regulation and differentiation (Blood, 4317-4326 (1997)); Angiogenic endothelial progenitors. Thus, certain drugs of formula I capable of blocking the kinase activity of endothelial cell-specific kinases are able to inhibit the progression of diseases involving these contexts.

A compound of formula I or a salt thereof or a pharmaceutical composition containing a therapeutically effective amount of the compound or a salt thereof is useful in the treatment of benign and neoplastic proliferative diseases and diseases of the immune system. Such diseases include autoimmune diseases such as rheumatoid arthritis, thyroiditis, type 1 diabetes, multiple sclerosis, sarcoidosis, inflammatory bowel disease, Crohn's disease, myasthenia gravis and systemic lupus erythematosus psoriasis, organ graft rejection (e.g., renal rejection, graft-versus-host disease rejection), benign and neoplastic proliferative diseases, human cancers such as lung, breast, stomach, bladder, colon, pancreas, ovary, prostate, and rectal cancer, and hematopoiesis Malignancies (leukemia and lymphoma), and diseases involving inappropriate vascularization such as diabetic retinopathy, retinopathy of prematurity, choroidal neovascularization due to age-related macular degeneration, and infantile hemangiomas in humans. In addition, the inhibitors are useful in the treatment of diseases associated with VEGF-mediated edema, ascites, leaks and exudates, including, for example, macular edema, cerebral edema, acute lung injury and adult respiratory distress syndrome (ARDS).

The compounds according to the invention are also suitable for the prophylaxis of the diseases mentioned above.

Another aspect of the present invention provides the use of a compound of formula I or a salt thereof in the preparation of a medicament for treating mammals, especially human, vascular hyperpermeability, angiogenesis-dependent diseases, proliferative diseases and/or immune system diseases.

The present invention also provides a method for treating vascular hyperpermeability, inappropriate neovascularization, proliferative diseases and/or immune system diseases, the method comprising administering a therapeutically effective amount of a compound of formula I to a mammal in need, especially a human .

The in vitro potency of compounds to inhibit these protein kinases can be determined as follows.

The potency of a compound can be determined by the amount of a test compound that inhibits phosphorylation of an exogenous substrate (eg, a synthetic peptide) relative to a control (Z. Songyang et al., Nature. 373:536-539).

Production of KDR tyrosine kinase using the baculovirus system:

The human KDR intracellular region coding sequence (aa789-1354) was generated by PCR using cDNAs isolated from HUVEC cells. A poly-His6 sequence was also introduced at the N-terminus of the protein. This fragment was cloned into the Xba 1 and Not 1 sites of the transfection vector pVL1393. Recombinant baculovirus (BV) was produced by co-transfection using BaculoGold transfection reagent (PharMingen). Recombinant BV plaques were purified and verified by Western analysis. For protein purification, 2×106/ml SF-9 cells were grown in SF-900-II medium and infected at 0.5 plaque-forming units/cell (MOI). Cells were harvested 48 hours after infection.

Purified KDR

By adding 50 ml Triton X-100 lysis buffer (20 mM Tris, pH 8.0, 137 mM NaCl, 10% glycerol, 1% Triton X-100, 1 mM PMSF, 10 μg/ml aprotinin to the cell pellet of 1 L cell culture enzyme, 1 μg/ml leupeptin), to lyse SF-9 cells expressing (His) ₆ KDR (aa789-1354). The lysate was centrifuged at 19,000 rpm in a Sorval SS-34 rotor at 4°C for 30 minutes. The cell lysate was packed on 5ml NiCl ₂ chelating agarose column, equilibrated with 50mM HEPES, pH7.5, 0.3M NaCl. KDR was eluted with the same buffer containing 0.25M imidazole. Column fractions were analyzed by SDS-PAGE and ELISA assay (below) measuring kinase activity. Purified KDR was exchanged in 25 mM HEPES, pH 7.5, 25 mM NaCl, 5 mM DTT buffer and stored at -80°C.

Production and purification of human Tie-2 kinase

The human Tie-2 intracellular region coding sequence (aa775-1124) was generated by PCR using cDNAs template isolated from human placenta. A poly-His6 sequence was introduced at the N-terminus and the assembly was cloned into the Xba 1 and Not 1 sites of the transfection vector pVL1939. Recombinant BV was produced by co-transfection using BaculoGold transfection reagent (PharMingen). Recombinant BV plaques were purified and verified by Western analysis. For protein purification, 2×106/ml SF-9 cells were grown in SF-900-II medium and infected at an MOI of 0.5. The His-tagged kinase used in the screening was purified following a method similar to that described for KDR.

Production and Purification of Human Flt-1 Tyrosine Kinase

The baculovirus expression vector pVL1393 (Phar Mingen, Los Angeles, CA) was used. The nucleotide sequence encoding poly-His6 was placed 5' to the nucleotide region encoding the intracellular kinase domain of the entire human Flt-1 (amino acids 786-1338). Using a cDNA library isolated from HUVEC cells, the nucleotide sequence encoding the kinase region was generated by PCR. The histidine residues made it possible to affinity purify the protein in a similar way to KDR and ZAP70. SF-9 insect cells were infected at a multiplicity of 0.5 and harvested 48 hours after infection.

EGFR tyrosine kinase source

EGFR was purchased from Sigma (Cat#E-3641; 500 units/50μl) and EGF ligand was obtained from Oncogene Research Products/Calbiochem (Cat#PF011-100).

Expression of ZAP70

The baculovirus expression vector used was pVL1393 (Pharmingen, Los Angeles, Ca.). The nucleotide sequence encoding amino acid M(H) _6LVPR9S was placed 5' to the region encoding the entire ZAP70 (amino acids 1-619). The nucleotide sequence encoding the ZAP70 coding region was generated by PCR using a cDNA library isolated from Jurkat immortalized T-cells. The histidine residues allow affinity purification of the protein (see below). The LVPR ₉ S bridge constitutes the recognition sequence for proteolytic cleavage by thrombin, making removal of the affinity tag feasible from the enzyme. SF-9 insect cells were infected at a multiplicity of 0.5 and harvested 48 hours after infection.

Extraction and purification of ZAP70

In a buffer consisting of 20 mM Tris pH 8.0, 137 mM NaCl, 10% glycerol, 1% TritonX-100, 1 mM PMSF, 1 μg/ml leupeptin, 10 μg/ml aprotinin, and 1 mM sodium orthovanadate , the SF-9 cells were lysed. The soluble lysate was loaded onto a chelating Sepharose HiTrap column (Pharmacia), equilibrated with 50 mM HEPES pH 7.5, 0.3 M NaCl. Fusion proteins were eluted with 250 mM imidazole. The enzyme is stored in a buffer containing 50mM HEPES pH 7.5, 50mM NaCl and 5mM DTT.

Source of Lck

Lck or truncated forms of Lck are commercially available (e.g. from Upstate Biotechnology Inc. (Saranac Lake, N.Y) and Santa Cruz Biotechnology Inc. (Santa Cruz, Ca.)) or purified from known natural or recombinant sources using conventional methods .

Enzyme-linked immunosorbent assay (ELISA) for PTKs

The presence of tyrosine kinase activity was determined and measured using an enzyme-linked immunosorbent assay (ELISA). The ELISA is performed according to known protocols described, for example, in Voller et al., 1980, "Enzyme-Linked Immunosorbent Assay": Manual of Clinical Immunology, 2nd Edition, edited by Rose and Friedman, pp 359-371 Am. Soc. of Microbiology, Washington, D.C.

Specific PTK activities were determined using the published protocol. For example, a preferred protocol for performing an ELISA experiment is provided below. Using these protocols to determine the activity of compounds against other receptor PTK family members and non-receptor tyrosine kinases is within the capabilities of those skilled in the art. To determine inhibitor selectivity, a general-purpose PTK substrate (e.g., poly(Glu ₄ Tyr) random copolymer, 20,000-50,000 MW) at a concentration approximately twice the apparent Km is combined with ATP (typically 5 μM) in the assay use together.

Inhibition of KDR, Flt-1, Flt-4/VEGFR-3, Tie-2, EGFR, FGFR, PDGFR, IGF-1-R, c-Met, and ZAP70 tyrosine kinase activity by compounds of the invention was assayed using the following procedure effect:

Buffers and solutions:

PGT poly(Glu,Tyr) 4:1

Store the powder at -20°C. The powder was dissolved in phosphate buffered saline (PBS) to make a 50 mg/ml solution. Store 1 ml aliquots at -20°C. When preparing plates, they were diluted to 250 μg/ml in GibcoPBS.

Reaction buffer: 100 mM Hepes, 20 mM MgCl ₂ , 4 mM MnCl ₂ , 5 mM DTT, 0.02% BSA, 200 μM NaVO ₄ , pH 7.10.

ATP: Store 100 mM aliquots at -20°C. Dilute to 20 μM in water

Wash buffer: PBS with 0.1% Tween 20

Buffer for antibody dilution: 0.1% bovine serum albumin (BSA) in PBS

TMB substrate: TMB substrate was mixed 9:1 with peroxide solution immediately before use or K-Blue substrate from Neogen was used.

Stop solution: 1M phosphoric acid

step

1. Board making:

PGT stock solution (50 mg/ml, frozen) was diluted to 250 μg/ml in PBS. 125 [mu]l was added to each well of a Corning modified flat bottom high affinity ELISA plate (Corning #25805-96). Add 125 μl PBS to blank wells. Cover with sealing tape and incubate overnight at 37°C. Wash once with 250 μl of washing buffer, and dry in a 37°C drying incubator for about 2 hours. Store encapsulated plates in sealed bags at 4°C until use.

2. Tyrosine kinase reaction:

- Prepare inhibitor solutions at 4x concentration in 20% DMSO in water.

- Preparation of reaction buffer

- Prepare the enzyme solution so that the desired unit is 50 μl, eg for KDR make 1 ng/μl for a total of 50 ng in each well in the reaction. Store on ice.

- Prepare 4x ATP in water from 100 mM stock solution. Store on ice.

- Add 50 μl of enzyme solution to each well (usually 5-50 ng enzyme/well depending on the specific activity of the kinase)

- Add 25 μl 4× inhibitor

- Add 25 μl 4xATP for inhibitor analysis

- Incubate at room temperature for 10 minutes

-Add 50μl 0.05N HCl to each well to stop the reaction

- washing board

**Final concentration of the reaction: 5 μM ATP, 5% DMSO

3. Antibody Binding

- Dilute an aliquot of 1 mg/ml PY20-HRP (Pierce) antibody (phosphotyrosine antibody) to 50 ng/ml in 0.1% BSA in PBS by two-step dilution (100x, then 200x)

- Add 100 μl Ab to each well. Incubate for 1 hour at room temperature. Incubate at 4°C for 1 hour.

- Wash 4x plates

4. Color reaction

- Prepare TMB substrate and add 100 μl to each well

- Monitor the OD value at 650nm until it reaches 0.6

- Stop the reaction with 1M phosphoric acid. Shake on plate reader.

- Immediate reading of OD value at 450nm

Optimal incubation time and enzyme reaction conditions vary slightly with enzyme preparations and are mostly determined empirically. For Lck, the reaction buffer used was 100 mM MOPSO, pH 6.5, 4 mM MgCl ₂ , 20 mM MgCl ₂ , 5 mM DTT, 0.2% BSA, 200 mM NaVO ₄ under similar analytical conditions.

The compounds of formula I are useful in the treatment of diseases associated with the inhibition of established protein tyrosine kinases, including those not mentioned above and which have not been identified, which are inhibited by the compounds of formula I. All compounds listed herein significantly inhibit KDR kinase at concentrations of 50 micromolar or less. Certain compounds of the present invention also significantly inhibit other PTKs such as lck at concentrations of 50 micromolar or less.

Cdc2 source

Human recombinant enzymes and assay buffers can be purchased (New England Biolabs, Beverly, MA. USA) or purified from known natural or recombinant sources by conventional methods.

Cdc2 assay

The protocol used was to use purchased reagents with minor changes. Briefly, in 50 mM Tris pH7.5, 100 mM NaCl, 1 mM EGTA, 2 mM DTT, 0.01% Brij, 5% DMSO supplemented with fresh 300 μM ATP (31 μCi/ml) and a final concentration of 30 μg/ml histone IIIss The reaction was carried out in a buffer consisting of 10 mM MgCl ₂ (commercial buffer). A volume of 80 μL containing enzyme units was allowed to react for 20 minutes at 25° C. in the presence or absence of inhibitors. The reaction was stopped by adding 120 μL of 10% acetic acid. Substrate was separated from unbound label by spotting the mixture on phosphocellulose paper, followed by three 5 min washes with 75 mM phosphoric acid. Count with a beta counter in the presence of liquid scintillator.

Certain compounds of the invention significantly inhibited cdc2 at concentrations below 50 uM.

PKC kinase source

The catalytic subunit PKC is commercially available (Calbiochem).

PKC kinase assay

Radioactive kinase assays were used according to published methods (Yasuda, I., Kirshimoto, A., Tanaka, S., Tominaga, M., Sakurai, A., Nishizuka, Y. Biochemical and Biophysical Research Communication 3: 166, 1220- 1227 (1990)). Briefly, all reactions were performed in kinase buffer consisting of 50 mM Tris HCl pH 7.5, 10 mM MgCl ₂ , 2 mM DTT, 1 mM EGTA, 100 μM ATP, 8 μM peptide, 5% DMSO and ³³ P ATP (8 Ci/mM) . Compounds and enzymes are mixed in a reaction vessel and the reaction is initiated by adding ATP and substrate mixture. After stopping the reaction by adding 10 [mu]L of stop buffer (5 mM ATP in 75 mM phosphoric acid), a portion of this mixture was spotted on phosphocellulose filter paper. Blotted samples were washed 3 times with 75 mM phosphoric acid at room temperature for 5-15 min each. Radiolabel binding was quantified by liquid scintillation counting.

Erk2 enzyme source

Recombinant mouse enzymes and assay buffers can be purchased (New England Biolabs, Beverly MA. USA) or purified from known natural or recombinant sources by conventional methods.

Erk2 enzyme assay

Briefly, under the conditions suggested by the supplier, in supplemented with fresh 100 μM ATP (31 μCi/ml) and 30 μM myelin basic protein, prepared by 50 mM Tris pH 7.5, 1 mM GTA, 2 mM DTT, 0.01% Brij, 5% The reaction was carried out in a buffer consisting of DMSO and 10 mM _MgCl2 (commercial buffer). Reaction volumes and bound radioactivity were determined as described above for the PKC assay (see above).

In vitro model of T-cell activation

Once activated by mitogens or antigens, T-cells are introduced to secrete IL-2, a growth factor that supports their subsequent proliferative phase. Thus, IL-2 production or cell proliferation of naive T-cells or appropriate T-cell lines can be measured as a surrogate for T-cell activation. All these assays are described in the literature and their parameters are fully cited (in Current Protocols in Immunology, Vol 2, 7.10.1-7.11.2).

Briefly, T-cell activation can be achieved by co-cultivation with allogeneic stimulator cells, a method known as the one-way mixed lymphocyte reaction. Effector and stimulator peripheral vascular mononuclear cells were purified by Ficoll-Hypaque gradient (Pharmacia) following the manufacturer's instructions. Stimulator cells were mitotically inactivated by treatment with mitomycin C (Sigma) or gamma irradiation. Effector and stimulator cells were co-cultured in a 2:1 ratio in the presence or absence of test compounds. Typically ¹⁰⁵ effectors were mixed with 5 x ¹⁰⁴ stimulators and plated (200 μl volume) in U-bottom microtiter plates (Costar Scientific). The cells were cultured in RPMI 1640 supplemented with heat-inactivated fetal calf serum (Hyclone Laboratories) or pooled human AB serum from a male blood donor, 5 x 10 ^-5 M 2-mercaptoethanol and 0.5% DMSO. The culture was pulsed with 0.5 μCi ^of3H -thymidine (Amersham) one day before harvest (usually day 3). Cultures were harvested (Betaplate harvester, Wallac) and assessed for isotope uptake by liquid scintillation (Betaplate, Wallac).

T-cell activation can be assessed by measuring IL-2 production using the same culture system. At 18-24 hours from the start of the culture, the supernatant was removed and IL-2 concentrations were measured by ELISA (R and D systems) following the manufacturer's instructions.

In vivo model of T-cell activation

The in vivo efficacy of compounds can be tested in animal models that directly measure T-cell activation or demonstrate inhibition as T-cell effectors. T-cells can be activated in vivo by complexing a constant ratio of T-cell receptors with monoclonal anti-CD3 antibodies (Abs). In this model, BALB/c mice were injected intraperitoneally with 10 μg of anti-CD3 Ab 2 hours before exsanguination. Animals were pre-dosed with a single dose of compound 1 hour prior to anti-CD3 Ab injection. Serum levels of the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), which are indicators of T-cell activation, were determined by ELISA. Using a similar model, T-cells are primed in vivo with specific antigens such as keyhole limpet hemocyanin (KLH), followed by depletion of lymph node cells with the same antigen for in vitro challenge. Cytokine production was measured to assess the activation status of cultured cells as described above. Briefly, on day 0, C57BL/6 mice were immunized subcutaneously with 100 μg of KLH emulsified in complete Freund's adjuvant (CFA). Animals were pre-treated with compound the day before immunization and were treated with compound on days 1, 2 and 3 after immunization. Depleted lymph nodes were harvested on day 4 and cultured in tissue culture medium (RPMI 1640 supplemented with heat-inactivated fetal bovine serum (Hyclone Laboratories), 5×10 ⁻⁵ M 2-mercaptoethanol, and 0.5% DMSO) at 6 The cells were cultured at a concentration of ×10 ⁶ /ml for 24-28 hours. Culture supernatants were then assessed for levels of the autocrine T-cell growth factors interleukin-2 (IL-2) and/or IFN-γ by ELISA.

The exemplified compounds are also tested in animal models of human disease. Examples include experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA). The EAE model simulating human multiple sclerosis has been described in both rats and mice (review FASEB J.5: 2560-2566, 1991; murine model: Lab.Invest.4(3): 278, 1981; rodent model: J. Immunol 146(4):1163-8, 1991). Briefly, mice or rats are immunized with an emulsion of myelin basic protein (MBP) or its neuropeptide derivatives and CFA. Acute disease can be caused by the addition of bacterial toxins such as B. pertussis. Relapsed/remitting disease was induced by adoptive transfer of T-cells from MBP/peptide immunized animals.

CIA can be induced in DBA/1 mice by immunization with type II collagen (J. Immunol: 142(7):2237-2243). Mice showed signs of arthritis as early as 10 days after antigen challenge and could be scored up to 90 days after immunization. In the EAE and CIA models, compounds are administered prophylactically or at the onset of disease. An effective drug should reduce the severity and/or incidence of disease.

Compounds of the invention that inhibit one or more angiogenic receptors PTK and/or protein kinases such as lck that mediate inflammatory responses can reduce the severity and incidence of arthritis in these animal models.

It can also be used in mouse allograft models, or skin (review, Ann. Rev. Immunol., 10: 333-58, 1992; Transplantation: 57 (12): 1701-17D6, 1994) or heart (Am. J. Anat.: 113:273, 1963) the compounds were tested in the transplantation model. Briefly, full thickness skin grafts were transplanted from C57BL/6 mice to BALB/c mice. Beginning on day 6, check daily for signs of graft rejection. In the mouse neonatal heart transplantation model, neonatal hearts were ectopically transplanted from C57BL/6 mice onto the pinnae of adult CBA/J mice. Hearts began to beat 4-7 days after transplantation, and a dissecting microscope was used to view cessation of beating to visually estimate rejection.

Cell Receptor PTK Analysis

The following cellular assays were used to determine the activity and level of effect of various compounds of the invention on KDR/VEGFR2. Similar receptor PTK assays using specific ligand stimulators can be designed following the same protocol as for other tyrosine kinases using techniques well known in the art.

VEGF-induced KDR phosphorylation in human umbilical vein endothelial cells (HUVEC) was measured by Western blotting:

1. HUVEC cells (from mixed blood donors) were purchased from Clonetics (San Diego, CA) and cultured according to the manufacturer's instructions. Only the early passages (passages 3-8) were used for this analysis. Cells were cultured in 100 mm dishes (Falcon for Tissue Culture; Becton Dickinson; Plymouth, England) using complete EBM medium (Clonetics).

2. In order to evaluate the inhibitory activity of the compounds, trypsin was applied to the cells, and the cells were seeded in each well of a 6-well cluster plate (Costar; Cambridge, MA) at an amount of 0.5-1.0×10 ⁵ cells/well.

3. 3-4 days after inoculation, the plate reaches 90-100% confluency. Remove the medium from all wells, rinse the cells with 5-10ml of PBS, and incubate with 5ml of EBM basal medium without additives (i.e., serum-free) for 18-24 hours.

4. Add serially diluted inhibitors to 1ml EBM medium (25μM, 5μM or 1μM final cell concentration) and incubate at 37°C for 1 hour. Human recombinant VEGF165 (R & D Systems) at a final concentration of 50 ng/ml in 2 ml of EBM medium was then added to all wells and incubated at 37°C for 10 minutes. Control cells, untreated or treated with VEGF only, were used to assess background phosphorylation and phosphorylation induced by VEGF. All wells were then rinsed with 5-10 ml of cold PBS containing 1 mM sodium orthovanadate (Sigma), the cells were lysed, and the wells were incubated with protease inhibitors (PMSF 1 mM, aprotinin 1 μg/ml, pepstatin 1 μg/ml) ml, 200 μl RIPA buffer (50 mM Tris-HCl pH 7, 150 mM NaCl, 1% NP-40, 0.25% deoxycholic acid Sodium, 1 mM EDTA) (all chemicals were obtained from Sigma Chemical Company, St Louis, MO). The lysate was spun at 14,000 rpm to remove nuclei.

An equal amount of protein was then precipitated by the addition of cold (-20°C) ethanol (2 volumes) for a minimum of 1 hour or a maximum of overnight. The pellet was reconstituted in Laemli sample buffer (BioRad; Hercules, CA) containing 5% mercaptoethanol and boiled for 5 minutes. Proteins were resolved by polyacrylamide gel electrophoresis (6%, 1.5 mm Novex, San Deigo, CA) and transferred to nitrocellulose membranes using the Novex system. After blocking with bovine serum albumin (3%), the protein was incubated at 4°C with anti-KDR polyclonal antibody (C20, Santa Cruz Biotechnology; Santa Cruz, CA) or with anti-phosphotyrosine monoclonal antibody (4G10, Upstate Biotechnology, Lake Placid, NY) probed overnight. After washing and incubation with HRP-conjugated F(ab) ₂ goat anti-rabbit or goat-anti-mouse IgG for 1 h, the spectra were visually inspected using an emission chemiluminescence (ECL) system (Amersham Life Sciences, Arlington Height, IL). bring. Certain embodiments of the invention significantly inhibited cellular VEGF-induced KDR tyrosine kinase phosphorylation at concentrations less than 50 [mu]M.

In vivo uterine edema model

The assay measures the compound's ability to inhibit the acute increase in uterine weight in mice that occurs within the first few hours after stimulation with estrogen. This early onset of uterine weight gain is known to be due to edema caused by increased permeability of the uterine vasculature. Cullinan-Bove and Koss (Endocrinology (1993), 133:829-837) demonstrated an intimate temporal relationship between estrogen-stimulated uterine edema and increased expression of VEGF mRNA in the uterus. These results have been demonstrated using a neutralizing monoclonal antibody against VEGF which significantly reduced the acute increase in uterine weight following estrogen stimulation (WO97/42187). Therefore, this system can be used as a model for the inhibition of VEGF signaling in vivo and the associated hyperosmolarity and edema.

Materials: All hormones were purchased from Sigma (St. Louis, MO) or Cal Biochem (La Jolla, CA) as lyophilized powders and prepared according to the supplier's instructions.

Vehicle components (DMSO, Cremaphor EL) were purchased from Sigma (St. Louis, MO).

Mice (Balb/c, 8-12 weeks old) were purchased from Taconic (Germantown, NY) and maintained in a pathogen-free animal husbandry facility according to public Animal Care and Use Committee Guidelines .

method:

Day 1: Balb/c mice were injected intraperitoneally (i.p.) with 12.5 units of pregnant mare's serum gonadotropin (PMSG).

Day 3: Mice received 15 units of human chorionic gonadotropin (hCG) intraperitoneally.

Day 4: Mice were randomly divided into groups of 5-10. Depending on solubility and vehicle, 1-100 mg/kg of test compound is administered by intraperitoneal or intravenous or oral routes. The vehicle control group received vehicle only, and two groups received no treatment.

Thirty minutes later, 17-estradiol (500 μg/kg) was intraperitoneally injected into the animals of the experimental group, the vehicle group and one untreated group. After 2-3 hours, sacrifice the animals by _CO inhalation. An incision was made along the midline, each uterus was separated, and excised below the cervix and at the junction of the uterus and the fallopian tubes. Fat and connective tissue were removed carefully without disrupting the integrity of the uterus and weighed (wet weight). Uterine fluid was blotted by squeezing the uterus between two sheets of filter paper with a 1-liter glass bottle filled with water. After blotting, the uterus was weighed (weight after blotting). The difference between the wet weight and the blotted weight is the fluid content of the uterus. The mean liquid content of the treated groups was compared to the untreated or vehicle treated groups. Significance was determined by Student's test. An unstimulated control group was used to monitor estradiol responses.

The results show that certain compounds of the invention inhibit edema formation when administered systemically by various routes.

Certain compounds of the invention that are inhibitors of angiogenic receptor tyrosine kinases also exhibit activity in the Matrigel implant model of neovascularization. The Matrigel model of neovascularization involves the formation of new blood vessels in a subcutaneously implanted clear "marble" extracellular matrix, which results from the presence of pro-angiogenic factors that generate tumor cells (see for example: Passaniti, A., et al. Lab.Investig.(1992), 67(4), 519-528; Anat.Rec.(1997), 249(1), 63-73; Int.J.Cancer(1995), 63(5), 694- 701; Vasc. Biol. (1995), 15(11), 1857-6). The model is preferably run for 3-4 days, and endpoints include macroscopic/visual scoring of neovascularization after excision of the implant, microvessel densitometry and quantitative analysis of hemoglobin relative to animals not treated with inhibitors ( Drabkin method). The model can also administer bFGF or HGF as stimuli.

Certain compounds of the invention that inhibit one or more oncogenes, proto-oncogenes, or proliferation-dependent protein kinases or angiogenic receptor PTKs also inhibit primary mouse, rat, or human xenograft tumors in mice growth or inhibit its metastasis in mouse models.

example

The core structures of the compounds of the invention were synthesized by base-catalyzed aldol condensation followed by elimination reactions. Reaction Scheme I is a general representation of this reaction. Suitable starting materials II and III for the synthesis of compounds of general formula IV of the present invention according to general reaction scheme I are commercially available and/or can be prepared according to methods well known in the art and/or as described herein.

Reaction Scheme I: General synthesis of 4-[(substituted)methylene]-2-pyrazolin-5-ones.

1. 4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one (V).

Example 1: 3-cyclopropyl-4-[(4,5-dimethylpyrrol-2-yl)methylene]-2-pyrazolin-5-one.

3-cyclopropyl-2-pyrazolin-5-one (790mg, 6.3mmol), 4,5-dimethylpyrrole-2-carbaldehyde (800mg, 6.5mmol) and 100mg piperidine in 50mL ethanol The reaction mixture was stirred at 90°C for 3.5 hours. The solvent was removed under reduced pressure. The solid residue was purified by flash column chromatography using (3:7) ethyl acetate:hexane as mobile phase, followed by further purification by recrystallization from toluene.

Example 40: 3-tert-butylureido-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one.

A mixture of 3-amino-4-[(pyrrol-2-yl)methylene]-2-pyrazolin-5-one (1.7 mmol) and tert-butyl isocyanate (1 mL) in 5 mL of ethyl acetate The reaction mixture was stirred at 80°C for 2 hours. The product was collected by filtration and recrystallized from ethanol.

Example 88: 4-{[4-(2-Dimethylaminoethoxycarbonyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-isopropoxy-2-pyrazole Lin-5-one.

4-[(4-carboxy-3,5-dimethylpyrrol-2-yl)methylene]-3 isopropoxy-2-pyrazolin-5-one (200mg, 0.68mmol) in A mixture of methyl chloride (20ml) and 1 drop of DMF was treated with oxalyl chloride (0.2ml). Stirring was continued for 24 hours and a solution of dimethylaminoethanol (0.6 g, 6.7 mmol) in dichloromethane (5 ml) was added. Stirring was continued for 24 hours. The solvent was evaporated to dryness, the solid residue was treated with _NaHCO3 (5%) and extracted with dichloromethane. The solid obtained after removal of the solvent was recrystallized from n-heptane.

Example 194: 4-{[4-(2-Diethylaminoethyl)-3,5-dimethylpyrrol-2-yl]methylene}-3-pyrazinyl-2-pyrazoline- 5-keto N-oxide

A mixture of EXAMPLE 176 (0.2 g, 0.54 mmol) and m-chloroperbenzoic acid (0.2 g, 1.1 mmol) in chloroform (50 mL) was stirred at room temperature for 48 hours. The solvent was removed to dryness and the residue was purified by flash chromatography (dichloromethane/ethanol 9:1). Yield 30%, melting point 192°C (ethanol).

Table 1: Other synthetic compounds of formula V Example Substituents on Ring A R ¹ recrystallization solvent Yield% method 1 4,5-Dimethyl Cyclopropyl Toluene 30 See Example 1 2 none Benzyl Toluene: Heptane 64 See Example 1 3 none 4-methoxyphenoxymethyl Methanol 36 See Example 1 4 none Phenoxymethyl NA 33 See Example 1 5 none 4-Chlorophenoxymethyl ethanol 33 See Example 1 6 none 4-methoxybenzyl ethanol twenty one See Example 1 7 4-(2-carboxyethyl)-3-methyl Benzyl NA See Example 1 8 3-(2-carboxyethyl)-4-methyl Benzyl Isopropanol See Example 1 9 none 4-Methylphenoxymethyl Methanol 42 See Example 1 10 none Amino Isopropanol 90 See Example 1 11 none Isopropoxy Isopropanol 52 See Example 1 12 none phenethyl NA 86 See Example 1 13 none aniline Isopropanol 86 See Example 1 14 none 4-Methylbenzyl Methanol 60 See Example 1 15 none 4-Methylaniline Methanol 86 See Example 1 16 none 4-methoxyanilino DMF: water 92 See Example 1 17 none 4-chlorobenzyl ethanol 56 See Example 1 18 none 4-Chloroanilino ethanol 90 See Example 1 19 none 3-Chlorophenoxymethyl NA 50 See Example 1 20 none Indol-3-yl ethanol 90 See Example 1 twenty one none 3-methoxybenzyl Methanol twenty one See Example 1 twenty two none 3,4-Dimethoxybenzyl ethanol 83 See Example 1 twenty three none 4-Ethoxyphenethyl ethanol 91 See Example 1 twenty four none 4-Phenylphenoxymethyl Methanol 72 See Example 1 25 none 2-Phenylpropyl Heptane 10 See Example 1 26 none 3-phenylpropyl Toluene: Heptane 60 See Example 1 27 none 4-Hydroxyphenethyl Methanol 76 See Example 1 28 3,5-Dimethyl phenethyl Methanol 51 See Example 1 29 none 4-Methylphenethyl ethanol 53 See Example 1 30 3,5-Dimethyl Isopropoxy Heptane 55 See Example 1 31 none Ethoxy ethanol 76 See Example 1 32 none 4-nitrophenethyl toluene 48 See Example 1 33 none 4-Fluoroanilino Isopropanol 66 See Example 1 34 none 4-Chlorophenethyl ethanol 60 See Example 1 35 4,5-Dimethyl Isopropoxy Methanol 55 See Example 1 36 3,5-Dimethyl-4-ethyl Isopropoxy Toluene 47 See Example 1 37 3,5-Dimethyl-4-ethyl phenethyl Heptane 49 See Example 1 38 1-(4-Hydroxybutyl) Isopropoxy NA 80 See Example 1 39 none Cyclopentyloxy Methanol 75 See Example 1 40 none tert-butylureido ethanol 87 See Example 40 41 4-Methyl Isopropoxy toluene 34 See Example 1 42 4-Methyl 4-Aminophenethyl NA 27 See Example 1 43 1-Methyl Isopropoxy toluene 55 See Example 1 44 5-methyl Isopropoxy Methanol: water 30 See Example 1 45 3,5-Dimethyl-4-ethyl 4-Aminophenethyl Toluene 50 See Example 1 46 5-methyl Ethoxy Methanol 58 See Example 1 47 3,5-Dimethyl-4-ethyl 4-carbamoylphenethyl DMF: water 82 See Example 1 48 3,5-Dimethyl-4-ethyl 4-Methoxycarbonylphenethyl Methanol 70 See Example 1 49 3,5-Dimethyl-4-ethoxycarbonyl Isopropoxy ethanol 81 See Example 1 50 3,5-Dimethyl-4-ethoxycarbonyl 4-Aminophenethyl ethanol 62 See Example 1 51 5-Ethyl Isopropoxy Heptane 48 See Example 1 52 3,5-Dimethyl-4-ethyl 4-Hydroxyphenethyl Isopropanol 35 See Example 1 53 none Ethoxycarbonylmethyl ethanol 35 See Example 1 54 none 4-Methoxyphenylaminocarbonylmethyl Methanol 46 See Example 1 55 3-(2-carboxyethyl)-4-methyl Isopropyl ethanol 32 See Example 1 56 none Cyclopropyl ethanol 50 See Example 1 57 none Cyclobutyl ethanol 65 See Example 1 58 none 3-pyridyl ethanol 50 See Example 1 59 1-(3,5-dichlorophenyl) Cyclopropyl ethanol 30 See Example 1 60 none 2,2,3,3-Tetramethylcyclopropyl toluene 55 See Example 1 61 3,5-Dimethyl Cyclopropyl toluene 33 See Example 1 62 none Cyclopentyl Toluene 66 See Example 1 63 none 2-methylcyclopropyl Hexane 44 See Example 1 64 none Benzothiazol-2-yl DMF: water 60 See Example 1 65 4,5-Dimethyl 3-pyridyl ethanol 35 See Example 1 66 3,5-Dimethyl-4-ethyl Cyclopropyl ethanol 50 See Example 1 67 none pyrrol-2-yl Methanol 88 See Example 1 68 4-Methyl Cyclopropyl ethanol 35 See Example 1 69 4-Methyl Benzothiazol-2-yl ethanol 48 See Example 1 70 3,5-Dimethyl 3-pyridyl ethanol twenty four See Example 1 71 3,5-Dimethyl-4-ethyl 3-pyridyl ethanol 51 See Example 1 72 5-methyl Cyclopropyl ethanol 50 See Example 1 73 5-methyl 3-pyridyl ethanol 47 See Example 1 74 5-Ethyl Cyclopropyl ethanol: water twenty one See Example 1 75 3,5-Dimethyl-4-ethoxycarbonyl Cyclopropyl ethanol 83 See Example 1 76 5-phenyl Isopropoxy Methanol 66 See Example 1 77 none Propyl NA 49 See Example 1 78 none methyl NA 6 See Example 1 79 none 4-Isopropylaniline NA 50 See Example 1 80 none 3-phenylamino NA 80 See Example 1 81 1-(4-Hydroxybutyl) Cyclopropyl ethanol 34 See Example 1 82 4-(2-carboxyethyl)-3-methyl Isopropoxy ethanol 46 See Example 1 83 4-carboxy-3,5-dimethyl Isopropoxy NA 41 See Example 1 84 4,5-tetramethylene Isopropoxy ethanol 77 See Example 1 85 3,4-Dimethyl-4-morpholinomethyl Isopropoxy NA 30 See Example 1 86 3,5-Dimethyl-4-dimethylaminomethyl Isopropoxy Heptane 30 See Example 1 87 4-acetyl-3,5-dimethyl Isopropoxy ethanol 62 See Example 1 88 3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl) Isopropoxy Heptane 40 See Example 88 89 3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl) Isopropoxy Toluene: Heptane 41 See Example 88 90 5-ethoxycarbonyl Isopropoxy Methanol 79 See Example 1 91 5-Carboxyl Isopropoxy Toluene 83 See Example 1 92 none 4-Chloroanilinocarbonylmethyl DMF/water 50 See Example 1 93 5-phenyl Cyclopropyl ethanol 72 See Example 1 94 3,5-Dimethyl-4-ethyl Tetrahydrofuran-3-yl toluene 44 See Example 1 95 4-carboxy-3,5-dimethyl Cyclopropyl ethanol 69 See Example 1 96 3,5-Dimethyl-4-ethoxycarbonyl 3-pyridyl ethanol 86 See Example 1 97 3,5-Dimethyl-4-morpholinomethyl Cyclopropyl NA 34 See Example 1 98 3,4-Dimethyl pyrazinyl Methanol 60 See Example 1 99 4-(2-carboxyethyl)-3-methyl Cyclopropyl Methanol 51 See Example 1 100 3,5-Dimethyl-4-dimethylaminomethyl Cyclopropyl NA 67 See Example 1 101 5-ethoxycarbonyl Cyclopropyl ethanol 91 See Example 1 102 4,5-tetramethylene Cyclopropyl ethanol 84 See Example 1 103 none 2-Methoxycarbonylethyl ethanol 56 See Example 1 104 none Ethoxycarbonyl NA 40 See Example 1 105 none Isopropyl NA 44 See Example 1 106 none trans-2-phenylcyclopropyl toluene 46 See Example 1 107 none Cyclohexyl toluene 32 See Example 1 108 4,5-tetramethylene Cyclopropylamino ethanol 50 See Example 1 109 5-morpholinomethyl Cyclopropyl ethyl acetate 72 See Example 1 110 5-Carboxyl Cyclopropyl ethanol 50 See Example 1 111 4-chloro Ethoxy ethanol 88 See Example 1 112 4-Bromo Ethoxy ethanol 70 See Example 1 113 5-chloro Ethoxy NA 37 See Example 1 114 4-chloro Cyclopropyl ethanol 42 See Example 1 115 4-Bromo Cyclopropyl ethanol 50 See Example 1 116 4,5-tetramethylene pyrazinyl ethanol 85 See Example 1 117 4,5-tetramethylene 3-pyridyl ethanol 84 See Example 1 118 4-carboxy-3,5-dimethyl pyrazinyl DMF 66 See Example 1 119 3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl) Cyclopropyl NA 71 See Example 88 120 3,5-Dimethyl-4-(2-dimethylaminoethoxycarbonyl) pyrazinyl NA 20 See Example 88 121 3,5-Dimethyl-4-dimethylaminomethyl pyrazinyl Toluene 76 See Example 1 122 3,5-Dimethyl-4-dimethylaminomethyl maleate pyrazinyl ethanol 98 Maleate salt formed from the free base of Example 121 (see footnote) 123 3,5-Dimethyl-4-(2-morpholinoethylaminocarbonyl) pyrazinyl Toluene 20 See Example 1 124 3,5-Dimethyl 2-pyridyl ethanol 36 See Example 1 125 3,5-Dimethyl-4-ethyl 2-pyridyl ethanol 50 See Example 1 126 4,5-tetramethylene 2-pyridyl ethanol 58 See Example 1 127 3,5-Dimethyl 2-furyl ethanol 51 See Example 1 128 3,5-Dimethyl-4-morpholinomethyl pyrazinyl NA 28 See Example 1 129 3,5-Dimethyl 2-thienyl ethanol 25 See Example 1 130 4-Ethoxycarbonyl Cyclopropyl ethanol 68 See Example 1 131 3,5-Dimethyl-4-trifluoroacetamidomethyl Cyclopropyl ethanol 70 See Example 1 132 4-aminomethyl-3,5-dimethyl Cyclopropyl ethanol 30 See Example 1 133 3,5-Dimethyl Benzothiazol-2-yl ethanol 40 See Example 1 134 3,5-Dimethyl-4-morpholinomethyl Benzothiazol-2-yl ethanol 40 See Example 1 135 3,5-Dimethyl-4-ethyl pyrazinyl ethanol 74 See Example 1 136 4-Ethoxycarbonyl pyrazinyl toluene 26 See Example 1 137 4-Carboxyl pyrazinyl Methanol 70 See Example 1 138 3,5-Dimethyl-4-diethanolaminomethyl pyrazinyl ethanol 50 See Example 1 139 3,5-Dimethyl-4-trifluoroacetamidomethyl pyrazinyl NA 78 See Example 1 140 4-ethoxycarbonyl-3-phenyl Cyclopropyl ethanol 68 See Example 1 141 3,5-Dimethyl-4-(1-pyrrolidinylmethyl) pyrazinyl Toluene twenty three See Example 1 142 3,5-Dimethyl-4-dimethylaminomethyl 2-furyl Toluene 20 See Example 1 143 3,5-Dimethyl-4-dimethylaminomethyl 2-thienyl toluene 48 See Example 1 144 3,5-Dimethyl-4-dimethylaminomethyl 3-pyridyl toluene 51 See Example 1 145 3,5-Dimethyl-4-ethoxycarbonyl Phenyl ethanol 89 See Example 1 146 3,5-Dimethyl-4-ethyl Phenyl Methanol 34 See Example 1 147 3,4-bis(ethoxycarbonyl) Ethoxy ethanol 54 See Example 1 148 4-Ethoxycarbonyl Ethoxy Methanol 30 See Example 1 149 3,5-Dimethyl-4-ethoxycarbonyl 2-(3-pyridyl)ethyl ethanol 81 See Example 1 150 3,5-Dimethyl-4-ethoxycarbonyl 1-methyl-2-phenylethyl ethanol 52 See Example 1 151 4-carboxy-3,5-dimethyl Ethoxy DMF: water 81 See Example 1 152 5-nitro Ethoxy ethanol 64 See Example 1 153 4-nitro Ethoxy Toluene 95 See Example 1 154 4-Carboxyl Ethoxy NA 40 See Example 1 155 3,5-Dimethyl-4-(2-dimethylaminoethylaminocarbonyl) Ethoxy Heptane 86 See Example 88 156 5-Chloro-3-methoxycarbonyl-4-methoxycarbonylmethyl Ethoxy ethanol 46 See Example 1 157 3-(2-carboxyethyl)-4-methyl Ethoxy NA 54 See Example 1 158 3,5-Dimethyl-4-ethoxycarbonyl Ethoxy ethanol 82 See Example 1 159 4,5-tetramethylene Ethoxy Heptane 80 See Example 1 160 3,5-Dimethyl-4-ethoxycarbonyl Trifluoromethyl ethanol 45 See Example 1 161 3,5-Dimethyl-4-ethoxycarbonyl 5-isoxazolyl DMF: water 74 See Example 1 162 3,5-Dimethyl-4-ethoxycarbonyl 3-aminophenyl ethanol 76 See Example 1 163 4-Morpholinoethylaminocarbonyl Ethoxy NA 30 See Example 88 164 4-ethoxycarbonyl-3-phenyl pyrazinyl toluene 70 See Example 1 165 4-(4-Methyl-1-piperazinylmethyl)-3,5-dimethyl pyrazinyl DMF 58 See Example 1 166 4-Diethylaminomethyl-3,5-dimethyl pyrazinyl NA 20 See Example 1 167 3,5-Dimethyl-4-piperidinomethyl pyrazinyl toluene 25 See Example 1 168 3,5-Dimethyl-4-piperidinomethyl 5-isoxazolyl NA 35 See Example 1 169 3,5-Dimethyl-4-dimethylaminomethyl 5-isoxazolyl NA 30 See Example 1 170 5-methyl-4-dimethylaminomethyl pyrazinyl Toluene-heptane 75 See Example 1 171 3,5-Dimethyl-4-[N-(2-dimethylaminoethyl)-N-methylaminomethyl] pyrazinyl Methanol 40 See Example 1 172 3-Dimethylaminomethyl-4,5-tetramethylene Cyclopropyl NA 30 See Example 1 173 3-Dimethylaminomethyl-4,5-tetramethylene pyrazinyl NA 30 See Example 1 174 3,5-Dimethyl-4-dimethylaminomethyl maleate Cyclopropyl ethanol 90 Maleate salt formed from the free base of Example 100 (see footnote) 175 4-(3-Chloropropionyl)-3,5-dimethyl pyrazinyl toluene 88 See Example 1 176 4-(2-Diethylaminoethyl)-3,5-dimethyl pyrazinyl ethanol 95 See Example 1 177 3,5-Dimethyl-4-(dimethylaminomethyl) 5-Methyl-3-isoxazolyl Toluene/heptane 40 See Example 1 178 3,5-Dimethyl-4-(4-hydroxypiperidinomethyl) pyrazinyl Methanol 40 See Example 1 179 4-aminomethyl-3,5-dimethylmaleate pyrazinyl Methanol 76 See Example 1 180 4-(4-Benzylpiperidinomethyl)-3,5-dimethyl pyrazinyl Toluene 80 See Example 1 181 3,5-Dimethyl-4-(2-hydroxyethyl) pyrazinyl NA 80 See Example 1 182 3,5-Dimethyl-4-[2-(1-pyrrolidinylethyl)] pyrazinyl Toluene 67 See Example 1 183 3,5-Dimethyl-4-[2-(1-pyrrolidinylethyl)] Cyclopropyl toluene 20 See Example 1 184 3,5-Dimethyl-4-(2-hydroxyethyl) Cyclopropyl NA twenty three See Example 1 185 3,5-Dimethyl-4-(2-ethylaminoethyl) pyrazinyl NA 35 See Example 1 186 4-(3-Diethylaminopropyl)-3,5-dimethyl pyrazinyl ethanol 52 See Example 1 187 3,5-Dimethyl-4-(3-hydroxypropyl) pyrazinyl ethanol 82 See Example 1 188 3,5-Dimethyl-4-dimethylaminoacetyl hydrochloride pyrazinyl ethanol/ether 51 See Example 1 189 3,5-Dimethyl-4-dimethylaminoacetyl Ethoxy ethanol/ether 44 See Example 1 190 4-(2-Diethylaminoethyl)-3,5-dimethyl Cyclopropyl Heptane 54 See Example 1 191 3,5-Dimethyl-4-(2-dimethylaminoethyl) pyrazinyl Toluene 48 See Example 1 192 3,5-Dimethyl-4-(4-hydroxybutyl) pyrazinyl Methanol 58 See Example 1 193 4-(4-Diethylaminobutyl)-3,5-dimethyl pyrazinyl Toluene 60 See Example 1 194 4-(2-Diethylaminoethyl-N-oxide)-3,5-dimethyl pyrazinyl ethanol 30 See Example 194 195 3,5-Dimethyl-4-(1-pyrrolidinylacetyl) pyrazinyl NA 57 See Example 1 196 4-Diethylaminoacetyl-3,5-dimethyl pyrazinyl NA 52 See Example 1 197 3-isopropyl-5-methyl pyrazinyl ethanol 44 See Example 1 198 3,5-Dimethyl-4-[3-(1-pyrrolidinylpropyl)] pyrazinyl ethanol 30 See Example 1 199 4-Dimethylaminomethyl-3-isopropyl-5-methyl pyrazinyl toluene 40 See Example 1 200 4-Dimethylaminomethyl-3-isopropyl-5-methyl Cyclopropyl toluene 40 See Example 1 201 3,5-Dimethyl-4-(2-ethoxyoxalyl) pyrazinyl ethanol 40 See Example 1 202 3,5-Dimethyl-4-(2-ethylaminoethyl) Cyclopropyl NA 60 See Example 1 203 3,5-Dimethyl-4-(2-cyclopropylaminoethyl) pyrazinyl toluene 40 See Example 1 204 3,5-Dimethyl-4-[2-(4-pyridylmethylamino)ethyl] pyrazinyl NA 40 See Example 1 205 3,5-Dimethyl-4-(2-cyclopropylaminoethyl) Cyclopropyl toluene 36 See Example 1 206 3,5-Dimethyl-4-(2-diethylaminoethyl) 2-pyrimidinyl toluene 35 See Example 1 207 3,5-Dimethyl-4-(2-diethylaminoethyl) 2-pyridazinyl toluene 40 See Example 1 208 3,5-Dimethyl-4-(2-diethylaminoethyl) 2-pyrimidinyl toluene 50 See Example 1 209 3,5-Dimethyl-4-(2-diethylaminoethyl) 2-pyridazinyl toluene 30 See Example 1

Table 1A: Physical data of synthesized compounds of formula V. Example Mp.(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 1 220-222 68.10 68.27 6.59 6.61 18.32 18.30 2 182-184 71.69 72.00 5.21 5.40 16.72 16.47 3 177-180 64.63 64.06 5.08 5.02 14.13 14.00 4 163-165 67.40 66.88 4.90 4.88 15.72 15.53 5 218-222 59.71 59.87 4.00 4.24 13.92 13.85 6 179-180 68.55 68.45 5.03 5.44 14.99 14.99 7 270-272 67.64 67.17 5.67 5.82 12.45 12.38 8( _0.3H2O ) ^* 226-228 66.58 66.10 5.72 5.65 12.26 12.27 9 207-210 68.31 68.20 5.37 5.44 14.93 14.96 10 265-270 54.53 55.07 4.57 4.47 31.80 31.98 11 172-174 60.26 60.37 5.97 5.80 19.16 18.97 12 145-147 72.43 72.29 5.69 5.70 15.83 16.17 13 285-287 66.65 66.66 4.79 4.71 22.20 22.12 14 254-255 72.43 72.36 5.69 5.53 15.83 15.84 15 256-258 67.65 67.31 5.29 5.12 21.03 20.96 16 288-290 63.81 63.90 4.99 4.53 19.84 19.75 17 178-180 63.05 63.26 4.23 4.10 14.70 14.59 18(0.25 H ₂ O) ^* 245-247 57.74 57.69 3.97 3.81 19.23 18.95 19 165-167 59.71 59.69 4.00 4.05 13.92 13.80 20 300.305 69.55 69.67 4.37 4.61 20.27 20.39 twenty one 169-171 68.31 68.27 5.37 5.36 14.93 14.92 twenty two 164-165 65.58 65.58 5.50 5.63 13.49 13.44 twenty three 137-139 69.13 69.15 5.80 5.69 14.22 14.30 24(0.25 H ₂ O) ^* 192.194 72.50 72.56 5.07 5.36 12.07 12.02 25 130.131 73.09 73.16 6.13 6.25 15.04 14.83 26 169-170 73.09 73.46 6.13 6.32 15.04 14.42 27 253-255 68.31 68.48 5.37 5.01 14.93 14.74 28 186-187 73.69 73.89 6.52 6.49 14.32 14.25 29 153-154 73.09 73.38 6.13 5.95 15.04 14.85 30 176-177 63.14 63.20 6.93 6.77 16.99 16.98 31 211-213 58.53 58.81 5.40 5.27 20.48 20.52 32 224-226 61.92 62.02 4.54 4.75 18.05 18.31 33 272-273 62.21 62.45 4.10 4.33 20.73 20.81 34 193-194 64.11 64.27 4.71 4.85 14.02 14.07 35 195-197 63.14 63.26 6.93 6.76 16.99 17.04 36 188-190 65.43 65.59 7.68 7.00 15.26 15.29 37 168-170 74.73 74.40 7.21 7.10 13.07 13.11 38 138-140 61.84 61.87 7.27 7.17 14.42 14.31 39 201-203 63.65 63.65 6.16 6.19 17.13 17.24 40 266-268 56.71 57.04 6.22 6.06 25.43 25.69 41 215-217 61.78 61.77 6.48 6.40 18.01 17.96 42(0.75 H ₂ O) ^* 178-180 66.32 66.78 6.33 6.01 18.19 17.85 43 199-201 61.78 61.97 6.48 6.36 18.01 17.91 44 128-130 61.78 61.42 6.48 6.32 18.01 17.78 45 183-185 71.40 71.38 7.19 7.28 16.65 16.62 46 197-199 64.35 64.69 7.33 6.96 16.08 16.03 47 297-299 69.21 69.08 6.64 6.68 15.37 15.31 48 177-179 69.64 69.70 6.64 6.57 11.07 11.10 49 226-228 60.18 60.06 6.63 6.46 13.16 13.02 50 186-188 66.30 66.20 6.36 6.25 14.73 14.68 51 119-121 63.14 63.14 6.93 6.95 16.99 17.00 52 260-262 71.19 71.01 6.87 6.96 12.45 12.36 53 124-126 58.29 58.49 5.29 5.04 16.99 16.99 54 240-242 62.95 62.96 4.97 5.00 17.27 17.11 55 229-231 62.26 62.20 6.62 6.37 14.52 14.36 56 158-160 65.65 65.78 5.51 5.50 20.88 20.78 57 150-152 66.95 67.09 6.03 5.76 19.52 19.45 58 222-224 65.53 65.57 4.23 4.29 25.51 23.62 59 188-190 58.97 59.06 3.78 3.92 12.13 11.98 60 160-162 70.01 70.28 7.44 7.35 16.33 16.22 61 193-195 68.09 68.34 6.59 6.39 18.32 18.18 62(0.2 toluene) ^* 127-129 69.82 69.73 6.75 6.64 16.96 17.20 63 132-133 66.95 67.11 6.08 6.03 19.52 19.73 64 340-342 61.20 61.38 3.42 3.70 19.03 19.19 65 220(d) 67.65 67.47 5.29 5.30 21.04 20.94 66 206-210 70.01 69.65 7.44 7.46 16.33 16.23 67 245-247 63.70 63.76 4.45 4.64 24.76 24.64 68 212-215 66.95 66.72 6.08 5.63 19.52 19.29 69( _0.5H2O ) ^* 327-329 60.55 60.90 4.12 4.09 17.65 17.42 70 235-238 67.65 67.66 5.29 5.40 21.04 20.98 71 270-272 69.36 69.41 6.16 6.21 19.03 18.98 72 170-172 66.95 67.05 6.08 6.08 19.52 19.42 73 210-212 66.65 66.73 4.79 4.82 22.21 22.10 74 163-165 68.10 68.15 6.59 6.63 18.32 18.27 75 240-242 63.77 63.77 6.35 6.35 13.94 13.90 76 212-214 69.14 69.27 5.80 5.88 14.23 14.20 77-80 ¹³ C and ¹ H NMR and analytical LC/MS data were consistent with the assigned structure 81 134-136 65.91 65.60 7.00 6.99 15.37 15.03 82 267-269 59.01 59.12 6.27 6.22 13.76 13.66 83 >300 57.72 57.81 5.88 5.84 14.42 14.25 84 206-207 65.91 66.04 7.01 6.78 15.37 15.34 85 162-164 62.41 62.36 7.56 7.46 16.17 15.94 86 173-175 63.13 63.27 7.95 7.73 18.41 18.34 87 209-210 62.27 61.86 6.62 6.58 14.52 14.25 88 165-167 59.65 59.82 7.23 7.05 15.46 15.34 89 192-194 59.82 59.92 7.53 7.26 19.38 19.21 90 205-207 57.72 57.96 5.88 5.62 14.42 14.43 91 235-237 51.24 51.78 5.38 5.49 14.94 14.95 92 240-242 58.45 58.07 3.98 3.96 17.04 16.64 93 208-210 73.62 73.60 5.45 5.62 15.15 15.14 94 163-165 66.87 66.70 7.36 7.10 14.62 14.59 95 312(d) 61.53 61.08 5.53 5.38 15.37 15.11 96 247-249 63.89 64.05 5.36 5.48 16.56 16.70 97 175-177 65.82 65.62 7.36 7.43 17.06 16.75 98 245-250 62.91 63.30 4.90 5.10 26.20 26.29 99 290(d) 62.70 62.66 5.96 5.83 14.62 14.47 100 176-178 67.10 67.21 7.74 7.49 19.56 19.53 101 250-152 61.52 61.73 5.53 5.46 15.37 15.40 102 227-230 70.56 70.62 6.71 6.61 16.46 16.52 103 134-136 58.29 58.71 5.29 5.44 16.99 17.03 104 177-179 56.64 56.85 4.75 4.56 18.01 17.56 105 120-122 65.01 65.12 6.44 6.44 20.67 20.59 106 173-175 74.42 74.20 5.60 5.77 14.46 14.77 107 176-178 69.11 69.21 7.04 7.08 17.27 17.24 108 240-243 66.64 66.62 6.71 6.39 20.72 20.80 109 184-186 63.98 64.21 6.71 6.69 18.65 18.74 110 220(d) 54.75 55.17 4.97 4.90 15.96 16.21 111 237-239 50.12 50.54 4.21 3.90 17.53 17.59 112 242-244 42.28 42.45 3.55 3.39 14.79 14.58 113 170-172 50.12 49.98 4.21 4.21 17.53 18.10 114 220(d) 56.06 56.46 4.27 4.37 17.83 17.54 115 210(d) 47.16 47.60 3.59 3.85 15.00 14.57 116 253-255 65.51 65.83 5.15 5.25 23.87 23.86 117 264-267 69.84 69.61 5.51 5.53 19.16 19.13 118 225-228 56.71 56.59 4.94 4.79 22.00 21.94 119 172-174 62.77 62.61 7.02 6.71 16.26 16.06 120 223-225 58.30 58.79 5.92 6.10 21.47 20.89 121 220-222 63.50 63.57 6.26 6.25 25.39 25.55 122 206-210 55.01 54.51 5.71 5.64 18.32 18.30 123 178-180 59.56 60.03 5.95 5.82 23.15 22.87 124 228-230 67.65 68.00 5.29 5.46 21.04 21.12 125 184-186 69.36 69.19 6.16 6.09 19.03 19.33 126 214-216 69.84 69.94 5.51 5.41 19.16 19.33 127 235-237 65.87 65.88 5.13 5.24 16.46 16.51 128 274-277 62.28 62.26 6.05 5.90 22.93 22.94 129 235-237 61.96 62.01 4.82 4.91 15.48 15.44 130 192-194 61.52 61.73 5.53 5.53 15.37 15.43 131 278-280 54.23 54.40 4.83 4.92 15.81 15.68 132 217-219 63.61 63.84 7.11 6.90 21.19 21.22 133 295-297 63.33 63.55 4.37 4.45 17.38 17.44 134 285(d) 62.15 62.03 5.54 6.02 16.47 16.91 135 264-267 65.06 65.10 5.80 5.71 23.71 23.51 136 155-157 59.74 59.30 4.46 4.40 21.24 21.20 137 230-232 54.26 54.58 3.77 3.34 24.34 23.99 138 242-244 58.44 58.81 6.36 6.28 21.52 21.84 139 302-305 51.45 51.30 3.93 4.26 21.17 20.88 140 218-220 68.75 69.07 5.48 5.53 12.02 11.96 141 235-237 64.02 64.11 6.41 6.54 23.58 23.01 142 209-211 65.36 65.37 6.45 6.89 17.93 16.53 143 208-210 61.32 61.43 6.20 6.18 16.83 16.64 144 220-224 66.85 67.24 6.54 6.54 21.65 21.11 145 216-217 67.64 67.71 5.68 5.80 12.45 12.53 146 274-275 73.70 73.80 6.53 6.53 14.32 14.39 147 132-134 55.01 55.24 5.48 5.32 12.03 12.03 148 212-216 56.31 56.25 5.45 5.20 15.15 15.02 149 180-182 65.56 65.10 6.05 5.96 15.29 15.20 150 168-170 69.64 69.91 6.64 6.43 11.07 11.10 151 310-312 56.31 56.30 5.45 5.15 15.15 15.17 152 208-210 48.00 48.37 4.03 4.19 22.39 22.65 153 287-289 48.00 48.37 4.03 4.04 22.39 22.64 154 290-293 53.01 52.63 4.45 4.47 16.86 16.59 155 158-160 58.61 58.82 6.94 6.48 16.08 16.05 156 225-227 48.72 49.00 4.36 4.18 11.36 11.35 157 255-257 57.72 57.65 5.88 5.97 14.42 14.32 158 232-234 59.01 59.06 6.27 6.30 13.76 13.68 159 178-180 64.85 64.61 6.61 6.95 16.20 15.99 160 252-254 51.07 51.17 4.29 4.34 12.76 12.60 161 255-257 58.53 58.63 4.91 5.08 17.06 16.96 162 214-216 64.76 64.91 5.72 5.74 15.90 15.74 163 197-199 56.50 56.22 6.41 6.37 19.38 18.96 164 255-257 65.11 65.37 4.42 4.49 18.08 18.11 165 295-297 63.31 63.62 6.64 6.66 25.84 25.96 166 242-244 64.75 64.66 6.86 6.73 23.85 23.74 167 240-242 65.91 65.61 6.64 6.74 23.06 22.69 168 215-217 63.79 63.57 6.44 6.56 19.38 19.82 169 161-163 56.45 56.96 6.51 6.45 20.57 20.29 170 193-195 61.92 62.18 5.85 5.74 27.08 26.80 171 205-207 62.96 62.48 7.13 6.73 25.70 25.40 172 182-185 69.20 69.21 7.74 7.82 17.93 17.41 173 210-212 65.12 64.66 6.33 6.02 23.98 23.50 174 199-201 59.68 59.31 6.51 6.37 13.92 14.42 175 213(d) 57.92 58.32 4.61 4.82 19.08 19.26 176 210-212 65.55 65.24 7.15 7.18 22.93 22.94 177 242-244 62.37 61.87 6.47 6.55 21.39 21.06 178( _0.5H2O ) ^* 255-57 61.68 61.48 6.47 6.45 21.58 21.68 179( _0.5H2O ) 205-8 54.15 54.27 5.02 4.97 19.94 19.63 180(0.25) 211-14 70.64 70.56 6.69 7.06 18.30 17.93 181 306-8 61.72 61.64 5.50 5.45 22.49 22.41 182 (0.17 H ₂ O) 190-92 65.36 64.97 6.67 6.55 22.86 23.20 183 197-200 69.90 69.87 8.02 8.12 17.16 16.86 184 244-46 65.91 65.52 7.00 6.98 15.37 15.05 185 192-94 HRMN and EM data are consistent with the specified structure 186(3.H ₂ O) 208.10 58.05 58.21 7.88 7.39 19.73 19.47 187 273-75 62.75 63.01 5.88 5.76 21.52 21.33 188(ClH.2H ₂ O) >300(d) 50.83 51.14 5.88 5.70 19.76 20.10 189 198 60.36 59.86 6.97 6.90 17.60 17.36 190 133 69.48 69.19 8.59 8.47 17.06 16.74 191 216 60.60 60.43 6.73 6.32 23.56 23.14 192 222 63.70 63.85 6.24 6.23 20.63 20.53 193 184 66.98 66.70 7.66 7.40 21.30 20.85 194 192 62.75 62.46 6.79 6.73 21.96 21.64 195( _0.5H2O ) 220 61.94 61.66 5.93 5.72 21.68 21.54 196( _0.5H2O ) 199 61.62 61.78 6.41 6.13 21.56 22.06 197 244 65.07 65.02 5.80 5.79 23.71 23.99 198 202-04 66.64 66.24 6.92 6.99 22.20 22.00 199 227 64.75 64.90 6.86 6.99 23.85 23.88 200 190-92 68.75 68.86 8.33 8.46 17.82 17.51 201 223 58.85 58.96 4.66 4.73 19.06 19.03 202( _0.4H2O ) 150 66.37 66.46 8.12 7.90 18.21 17.80 203 210-218 63.81 63.95 6.42 6.45 23.50 23.12 204( _0.2H2O ) 203-205 65.23 65.05 5.82 5.84 24.20 23.77 205( _0.4H2O ) 158-160 67.64 67.93 7.81 7.74 17.53 17.40 206( _0.2H2O ) 144-146 64.91 64.87 7.19 7.30 22.71 22.53 207( _0.2H2O ) 218-220 64.91 64.79 7.19 7.00 22.71 22.78 208 220 65.55 65.45 7.15 7.13 22.93 22.53 209 212-216 65.55 65.49 7.15 7.38 22.93 22.31

^* For elemental analysis, calculated molecular weights include the indicated amounts of solvent.

Footnote: The maleate salt was formed by adding an ethanolic solution of maleic acid to the free base in ethanol at room temperature, then cooled, and the crystallized product was filtered.

II. 4-[(Indol-3-yl)methylene]-2-pyrazolin-5-one (VI).

Example 210: 3-Benzyl-4-[(indol-3-yl)methylene]-2-pyrazolin-5-one.

A reaction mixture of 3-benzyl-2-pyrazolin-5-one (905mg, 5.2mmol), 3-indolecarbaldehyde (800mg, 5.6mmol) and piperidine (100mg) in ethanol (50mL) was heated at 90 °C and stirred for 3 hours. After cooling overnight, the product was collected by filtration and purified by recrystallization from ethanol.

Table 2: Other synthetic compounds of formula VI. Example Substituents on indole R ¹ recrystallization solvent Yield% method 210 none Benzyl ethanol 76 See Example 210 211 1-(4-Hydroxybutyl) Benzyl Methanol 51 See Example 210 212 none 4-methoxyphenoxymethyl Isopropanol 67 See Example 210 213 none Phenoxymethyl Isopropanol 94 See Example 210 214 none 4-Chlorophenoxymethyl ethanol 65 See Example 210 215 none 4-methoxybenzyl ethanol 90 See Example 210 216 none 4-Methylphenoxymethyl ethanol 93 See Example 210 217 none phenethyl ethanol 84 See Example 210 218 none Isopropyl Methanol 81 See Example 210 219 none 4-Methylbenzyl ethanol 95 See Example 210 220 none aniline Isopropanol 52 See Example 210 221 none 4-Methylaniline Methanol 60 See Example 210 222 none 4-methoxyanilino ethanol 96 See Example 210 223 none 4-chlorobenzyl ethanol 77 See Example 210 224 1-(4-Hydroxybutyl) 4-methoxybenzyl DMF: water 89 See Example 210 225 none 4-Chloroanilino DMF: water 86 See Example 210 226 none 3-methoxybenzyl DMF: water 99 See Example 210 227 none 3,4-Dimethoxybenzyl DMF: water 88 See Example 210 228 none 4-Hydroxybenzyl DMF: water 56 See Example 210 229 none 3-Chlorophenoxymethyl Isopropanol 89 See Example 210 230 none Indol-3-yl Methanol 58 See Example 210 231 none 4-methoxyphenethyl Isopropanol 88 See Example 210 232 none 4-Phenylphenoxymethyl NA 91 See Example 210 233 none 2-Phenylpropyl Methanol 60 See Example 210 234 none 3-phenylpropyl ethanol 76 See Example 210 235 none 4-Hydroxyphenethyl Methanol 51 See Example 210 236 none 4-Methylphenethyl ethanol 86 See Example 210 237 none Ethoxy ethanol 90 See Example 210 238 1-(4-Hydroxybutyl) Isopropoxy Toluene: Heptane 43 See Example 210 239 1-(4-Hydroxybutyl) phenethyl Methanol 80 See Example 210 240 none 4-nitrophenethyl Isopropanol 83 See Example 210 241 none Propoxy DMF: water 43 See Example 210 242 none 4-Fluoroanilino ethyl acetate 65 See Example 210 243 none 4-Aminophenethyl Methanol: water 74 See Example 210 244 2-methyl Isopropoxy Methanol 40 See Example 210 245 7-Methyl Isopropoxy ethanol 98 See Example 210 246 7-Methyl phenethyl DMF: water 97 See Example 210 247 none Cyclopentyl ethanol 56 See Example 210 248 1-Methyl Isopropoxy ethanol 81 See Example 210 249 none 4-Methoxycarbonylphenethyl ethanol 77 See Example 210 250 1-isopropyl Isopropoxy Toluene: Heptane 71 See Example 210 251 1-Methyl 4-Hydroxyphenethyl ethanol 50 See Example 210 252 none Isopropyl ethanol 76 See Example 210 253 none 4-Chloroanilinocarbonylmethyl DMF: water 40 See Example 210 254 none Ethoxycarbonylmethyl Methanol 40 See Example 210 255 none 4-Methoxyphenylaminocarbonylmethyl DMF: water 40 See Example 210 256 none Cyclopropyl DMF: water 50 See Example 210 257 none 3-pyridyl ethanol 50 See Example 210 258 none 2-Aminocarbonylethyl Methanol 55 See Example 210 259 none Cyclobutyl ethanol 79 See Example 210 260 none 2-(Dimethylaminocarbonyl)ethyl ethanol 97 See Example 210 261 1-(4-Hydroxybutyl) Cyclopropyl ethanol 80 See Example 210 262 none 4-pyridyl ethanol 91 See Example 210 263 none Cyclopentyl ethanol 75 See Example 210 264 none 2,2,3,3-Tetramethylcyclopropyl ethanol 32 See Example 210 265 none 2-methylcyclopropyl ethanol 34 See Example 210 266 1-(4-Hydroxybutyl) Cyclohexyl toluene 41 See Example 210 267 1-(4-Hydroxybutyl) 4-pyridyl ethanol 50 See Example 210 268 none Benzothiazol-2-yl ethanol 50 See Example 210 269 none 2-pyridyl 67 See Example 210 270 none Dimethylamino ethanol 77 See Example 210 271 none pyrrol-2-yl ethanol 83 See Example 210 272 none 6-methoxybenzothiazol-2-yl ethanol 60 See Example 210 273 1-Methyl Cyclopropyl ethanol 76 See Example 210 274 7-Methyl Cyclopropyl ethanol 60 See Example 210 275 1-Methyl 3-pyridyl ethanol 64 See Example 210 276 none Propyl NA 63 See Example 210 277 none methyl NA 68 See Example 210 278 none Trifluoromethyl NA 14 See Example 210 279 1-(4-Hydroxybutyl) hydrogen NA 62 See Example 210 280 1-(4-Hydroxybutyl) methyl NA 36 See Example 210 281 1-(4-Hydroxybutyl) Trifluoromethyl NA 7 See Example 210 282 1-(4-Hydroxybutyl) tert-butyl NA 50 See Example 210 283 none Ethoxycarbonyl ethanol 74 See Example 210 284 none 2-Methoxycarbonylethyl ethanol 79 See Example 210 285 none trans-2-phenyl-1-cyclopropyl ethanol 92 See Example 210 286 1-(4-Hydroxybutyl) Cyclobutyl ethanol 26 See Example 210 287 6-carboxy-1-methyl Cyclopropyl ethanol 26 See Example 210 288 5-methoxy-1-methyl Cyclopropyl ethanol 75 See Example 210 289 1-Methyl pyrazinyl ethanol 82 See Example 210 290 1,7-Dimethyl Cyclopropyl ethanol 97 See Example 210 291 1-Methyl Tetrahydrofuran-3-yl ethanol 78 See Example 210 292 1-Methyl Cyclopropylamino ethanol 54 See Example 210 293 6-carboxy-1-methyl Isopropoxy DMF: water 45 See Example 210 294 1,7-Dimethyl Isopropoxy Methanol 53 See Example 210 295 5-methoxy-1-methyl Isopropoxy ethanol 72 See Example 210 296 1-Methyl 4-Fluoroanilino Methanol 80 See Example 210 297 1-Methyl Trifluoroacetamido Methanol 70 See Example 210 298 1-Methyl 4-Aminophenethyl toluene 64 See Example 210 299 1-Methyl Amino ethanol 80 See Example 210 300 none 4-Chlorophenethyl ethanol 85 See Example 210 301 1-Methyl Ethoxy ethanol 80 See Example 210 302 1-Methyl 5-isoxazolyl DMF: water 83 See Example 210 303 1-Methyl tert-butyl ethanol 92 See Example 210 304 6-carboxy-1-methyl pyrazinyl DMF 98 See Example 210 305 1-methyl-6-[2-(4-morpholino)ethyl]aminocarbonyl pyrazinyl NA 20 See Example 210

Table 2A: Physical data of synthesized compounds of formula VI. Example Mp.(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 210 292-295 75.73 75.74 5.02 5.28 13.94 13.85 211 217-220 73.97 73.93 6.20 6.14 11.25 11.18 212 266-268 69.35 69.23 4.65 5.05 12.13 12.03 213 284-286 71.91 71.86 4.76 4.78 13.24 13.34 214 264-267 64.87 64.78 4.01 4.12 11.94 11.93 215 265-270 72.49 72.64 5.17 5.21 12.68 12.72 216 288-291 72.49 72.52 5.17 5.36 12.68 12.74 217 268-270 76.17 76.12 5.43 5.55 13.32 13.59 218 263-265 66.90 66.75 5.61 5.46 15.60 15.48 219 280-282 76.17 76.34 5.43 5.23 13.32 13.30 220 265-267 71.50 71.48 4.66 4.62 18.53 18.35 221 (0.75 H ₂ O) ^* 255-257 69.11 69.30 5.30 5.07 16.98 16.99 222 265-267 68.66 68.65 4.85 4.98 16.85 16.67 223 274-277 67.96 67.77 4.20 4.39 12.51 12.33 224 204-206 71.44 71.39 6.24 6.14 10.41 10.32 225 248-250 64.19 64.01 3.89 4.15 16.63 16.59 226 288-290 72.49 72.46 5.17 5.16 12.68 12.81 227 282-284 69.79 69.68 5.29 5.29 11.62 11.75 228 295-300 71.91 71.20 4.76 4.76 13.24 13.44 229 265-268 64.87 64.91 4.01 4.16 11.94 11.92 230( _0.5CH3OH ) ^* 288-292 71.91 71.455 4.71 4.69 16.36 13.36 231 266-268 73.02 72.78 5.54 5.70 12.16 12.09 232(0.75 H ₂ O) ^* 295-296 73.78 73.58 5.07 5.21 10.32 10.20 233 253-255 76.57 76.06 5.81 6.09 12.75 12.60 234 218-220 76.57 76.52 5.81 5.93 12.75 12.62 235(1.0CH ₃ OH) ^* 271-275 69.40 69.40 5.82 5.72 11.56 11.38 236 244-245 76.57 76.73 5.81 5.72 12.75 12.64 237 248-250 65.87 65.94 5.13 5.01 16.46 16.45 238 210-212 66.84 66.76 6.79 6.83 12.30 12.21 239 205-207 74.39 74.32 6.50 6.58 10.84 10.92 240 295-297 66.65 66.65 4.47 4.85 15.54 15.75 241 246-247 66.90 66.95 5.61 5.56 15.60 15.61 242(0.75 ethyl acetate) ^* 251-252 65.28 64.88 4.92 4.91 14.50 14.53 243 244-246 72.70 72.45 5.49 5.67 16.95 16.71 244(0.25CH ₃ OH) ^* 262-264 66.99 66.78 6.22 6.09 14.42 14.46 245 254-256 67.82 67.78 6.04 5.76 14.83 14.82 246 302-304 76.57 75.96 5.81 5.59 12.75 12.84 247 277-279 69.13 68.95 5.80 5.79 14.22 14.36 248 239-240 67.82 67.75 6.04 6.10 14.83 14.77 249 259-260 70.76 70.62 5.13 5.43 11.25 11.24 250 161-163 69.43 69.40 6.75 6.80 13.49 13.48 251 255-257 73.04 72.89 5.50 5.72 12.17 12.11 252 264-266 71.12 71.17 5.96 5.87 16.58 16.65 253 305-307 63.41 63.17 3.99 4.07 14.79 14.57 254 235-237 64.63 64.81 5.08 5.04 14.13 14.22 255( _0.5H2O ) ^* >300 65.78 65.64 4.99 4.81 14.61 14.61 256 300-305 71.69 71.39 5.21 5.22 16.72 16.75 257 305-307 70.82 70.71 4.36 4.36 19.43 19.50 258 280-281 61.58 61.86 5.29 5.44 18.36 18.12 259 >300 72.43 72.30 5.69 5.71 15.84 15.85 260 258-260 65.79 65.66 5.84 5.50 18.05 17.82 261 215-216 70.56 70.29 6.54 6.45 12.99 12.99 262 >300 70.82 70.76 4.19 4.78 19.43 19.29 263 300-304 73.09 72.79 6.13 6.06 15.04 14.98 264(0.25 H ₂ O) ^* 296-298 73.16 73.43 6.86 6.89 13.47 13.36 265 294-296 72.43 72.57 5.69 5.73 15.84 15.85 266 226-227 72.29 72.10 7.44 7.56 11.49 11.54 267 224-225 68.27 68.65 5.73 5.91 15.16 15.25 268 >300 66.26 65.96 3.51 3.64 16.27 16.25 269 278-280 70.82 71.07 4.19 4.35 19.43 19.53. 270 258-260 66.12 66.26 5.54 5.50 22.03 21.87 271 300-302 69.55 68.91 4.37 4.54 20.28 20.23 272 >300 64.16 64.20 3.77 3.94 14.96 14.69 273 245-247 72.43 72.34 5.69 5.72 15.83 15.78 274 286-288 72.73 72.14 5.69 5.91 15.83 15.60 275( _0.5H2O ) ^* 230-232 69.44 69.89 4.85 4.84 17.99 18.10 276-282 ¹³ C and ¹ H NMR and analytical LC/MS data were consistent with the assigned structure 283 250(d) 63.59 63.42 4.62 5.00 14.83 14.83 284 267-269 64.63 64.58 5.08 5.29 14.13 14.14 285 280-282 75.99 76.11 5.31 5.32 12.66 12.65 286 220-222 71.19 71.16 6.87 6.85 12.45 12.46 287 237-240(d) 66.00 66.00 4.88 4.85 13.58 13.43 288 236-238 67.09 67.48 5.96 6.00 13.80 13.76 289 263-265 67.31 67.58 4.32 4.48 23.09 23.31 290 258-260 72.15 72.33 6.22 6.06 14.85 15.11 291 208-210 69.13 69.18 5.80 5.85 14.23 14.25 292 160-164(d) 68.55 68.25 5.75 5.86 19.98 19.71 293 330-332 62.38 62.37 5.23 5.31 12.84 12.87 294 245-247 68.67 68.86 6.44 6.21 14.13 14.14 295 238-239 65.16 65.31 6.11 6.10 13.41 13.46 296 218-219 67.09 66.65 4.82 4.99 16.12 16.10 297 252-253 53.58 53.80 3.30 3.51 16.66 16.67 298 192-193 74.29 74.26 5.98 5.85 15.27 15.38 299 246-247 63.73 63.51 5.10 5.32 22.88 22.54 300 271-272 68.67 68.59 4.61 5.04 12.01 11.81 301 194-196 66.90 66.94 5.61 5.72 15.60 15.62 302 271-272 65.75 66.02 4.14 4.34 19.17 19.00 303 201-203 70.28 70.02 7.44 7.41 13.29 13.17 304 >300 60.47 60.96 4.54 4.33 20.02 19.85 305 240-241 61.52 61.67 5.59 5.67 20.92 20.91

^* For elemental analysis, calculated molecular weights include the indicated amounts of solvent.

Footnote: The maleate salt was formed by adding an ethanolic solution of maleic acid to the free base in ethanol at room temperature, then cooled, and the crystallized product was filtered.

III. 4-[(Indol-2-yl)methylene]-2-pyrazolin-5-one (VII).

Table 3: Synthesized compounds of formula VII. Example Substituents on indole R ¹ recrystallization solvent Yield% method 306 none Isopropoxy ethanol 81 See Example 210 307 none 4-Hydroxyphenethyl ethanol 45 See Example 210 308 none 4-Aminophenethyl NA 20 See Example 210 309 none 4-Methoxycarbonylphenethyl toluene 75 See Example 210 310 none 4-carbamoylphenethyl DMF: water 90 See Example 210 311 none Cyclopropyl ethanol 35 See Example 210 312 3-Dimethylaminomethyl Cyclopropyl NA 20 See Example 210 313 none 3-pyridyl ethanol 62 See Example 210 314 5-methoxy Isopropoxy Methanol 78 See Example 210 315 1-Methyl Isopropoxy DMF: water 89 See Example 210 316 none Tetrahydrofuran-3-yl ethyl acetate 30 See Example 210 317 5-methoxy Cyclopropyl ethanol 33 See Example 210 318 5-nitro Cyclopropyl DMF 84 See Example 210 319 none Isopropylamino Methanol 80 See Example 210 320 none 4-carboxyphenethyl DMF: water 65 See Example 210 321 none Phenyl ethanol 55 See Example 210 322 3-methyl Isopropoxy Methanol 76 See Example 210 323 3-(2-methoxycarbonyl-2-acetamidoethyl) Isopropoxy Toluene: Heptane 40 See Example 210 324 none Ethoxy ethanol 55 See Example 210 325 3-(4-morpholinomethyl) Ethoxy ethanol 65 See Example 210 326 3-(4-morpholinomethyl) Cyclopropyl ethyl acetate 46 See Example 210 327 5-methoxy pyrazinyl NA 91 See Example 210 328 5-methoxy 2-pyridyl NA 90 See Example 210 329 4-chloro-6,7-dihydro Ethoxy ethanol 54 See Example 210 330 4-chloro-6,7-dihydro pyrazinyl Toluene 83 See Example 210 331 4-oxo-1,5,6,7-tetrahydro pyrazinyl toluene 40 See Example 210 332 3-Dimethylaminomethyl Ethoxy Toluene-heptane 41 See Example 210

Table 3A: Physical data of synthesized compounds of formula VII. Example Mp.(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 306 221-223 66.90 67.11 5.61 5.53 15.60 15.68 307 242-245 72.49 72.34 5.17 5.15 12.68 12.36 308 187-189 72.71 72.99 5.49 5.48 16.96 16.35 309 210-212 70.76 70.99 5.13 5.00 11.25 11.11 310( _0.25H2O ) ^* 263-265 69.44 69.51 5.09 5.05 15.43 15.21 311( _0.75H2O ) ^* 238-240 68.04 67.68 5.55 5.11 15.87 15.75 312( _0.25H2O ) ^* 202(d) 69.10 69.13 6.60 6.46 17.91 17.56 313( _0.5H2O ) ^* 155-157 68.67 68.68 4.40 4.48 18.84 18.56 314 219-220 64.20 64.48 5.72 5.76 14.04 14.08 315 254-255 67.83 67.89 6.05 6.09 14.83 14.83 316 180-183 68.31 68.49 5.37 5.57 14.94 14.80 317 221-224 68.31 68.34 5.37 5.35 14.94 14.82 318 316-320 60.80 60.70 4.08 4.35 18.91 19.01 319 245-247 67.14 67.08 6.01 6.03 20.88 20.94 320 >300 70.18 69.87 4.77 4.87 11.69 11.76 321 210-211 75.25 75.17 4.56 4.75 14.62 14.62 322 241-243 67.83 67.97 6.05 6.05 14.83 14.89 323 205-206 61.16 61.51 5.87 5.93 13.58 13.27 324 265-267 65.87 65.91 5.13 5.27 16.46 16.52 325 205-206 64.39 64.64 6.26 6.35 15.81 15.82 326 203-180 68.55 68.53 6.32 6.31 15.99 15.80 327 272-274 63.94 64.29 4.10 4.00 21.93 22.10 328 170-172 67.91 68.06 4.43 4.43 17.60 17.74 329 177-203 57.64 57.87 4.84 4.79 14.40 14.35 330(0.4 toluene) ^* 206-209 62.27 62.20 4.22 4.47 19.31 19.27 331 (0.1 toluene) ^* 300-303 63.36 63.49 4.36 4.41 22.12 21.96 332 185-187 65.37 65.13 6.45 6.35 17.94 17.70

^* For elemental analysis, calculated molecular weights include the indicated amounts of solvent.

IV. 4-[(7-Azaindol-3-yl)methylene]-2-pyrazolin-5-one (VIII).

Table 4: Synthesized compounds of formula VIII. Example Substituents on azaindole R ¹ recrystallization solvent Yield% method 333 none Benzyl DMF: water 71 See Example 210 334 1-(4-Hydroxybutyl) Benzyl ethyl acetate 30 See Example 210 335 none 4-methoxyphenoxymethyl DMF: water 80 See Example 210 336 none Isopropoxy Methanol 61 See Example 210 337 none Amino DMF: water 92 See Example 210 338 none 4-methoxybenzyl DMF: water 96 See Example 210 339 none aniline DMF: water 77 See Example 210 340 none 4-Methylbenzyl ethanol 95 See Example 210 341 none 4-Hydroxyphenethyl ethanol 84 See Example 210 342 1-(4-Hydroxybutyl) 4-Hydroxyphenethyl Methanol 80 See Example 210 343 none Isopropyl ethanol 30 See Example 210 344 none Cyclopropyl ethanol 50 See Example 210 345 none Cyclobutyl ethanol 74 See Example 210 346 none 3-pyridyl ethanol 40 See Example 210 347 none Phenyl NA 56 See Example 210 348 none 4-Fluoroanilino NA 14 See Example 210 349 none Propyl NA twenty four See Example 210 350 none methyl NA 77 See Example 210 351 none Trifluoromethyl NA 17 See Example 210 352 none tert-butyl NA 80 See Example 210 353 1-(4-Hydroxybutyl) Trifluoromethyl NA 6 See Example 210 354 none 4-Isopropylaniline NA 30 See Example 210 355 none 3-Methylaniline NA 70 See Example 210 356 1-(4-Hydroxybutyl) 3-Methylaniline NA 30 See Example 210 357 none phenethyl DMF: water 63 See Example 210

Table 4A: Physical data of synthesized compounds of formula VIII. Example Mp.(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 333 274-277 71.50 71.63 4.66 4.88 18.53 18.17 334 176-179 70.56 70.67 5.92 5.87 14.96 14.78 335 300-302 65.69 65.62 4.35 4.85 16.12 15.77 336 258-260 62.21 61.57 5.22 5.12 20.72 20.57 337(1H ₂ O) ^* >300 53.82 53.92 4.48 4.34 28.54 28.22 338 273-276 68.66 68.05 4.85 4.89 16.85 16.67 339(1H ₂ O) ^* 249-252 63.54 63.45 4.70 4.75 21.79 21.68 340( _0.5H2O ) ^* >300 70.07 70.54 5.22 5.07 17.21 17.24 341 270-272 68.66 68.25 4.85 5.04 16.86 16.71 342 211-212 68.30 67.97 5.98 6.11 13.85 13.80 343 300(d) 66.12 65.91 5.54 5.57 22.03 21.89 344( _0.25H2O ) ^* 245-246 65.48 65.20 4.90 4.76 21.82 21.47 345 300-302 66.52 66.51 5.39 5.22 20.69 20.88 346 212-215 66.50 65.84 3.83 4.07 24.20 23.93 347 280-282 70.80 70.50 4.20 4.10 19.40 19.10 348-356 ¹³ C and ¹ H NMR and analytical LC/MS data were consistent with the assigned structure 357 317-319 72.13 71.69 5.09 5.04 17.70 17.65

^* For elemental analysis, calculated molecular weights include the indicated amounts of solvent.

Footnote: The maleate salt was formed by adding an ethanolic solution of maleic acid to the free base in ethanol at room temperature, then cooled, and the crystallized product was filtered.

V. 4-(Phenylmethylene)-2-pyrazolin-5-one (IX).

Table 5: Synthesized compounds of formula IX. Example Substituents on Ring A R ¹ recrystallization solvent Yield% method 358 4-Dimethylamino Benzyl ethanol 32 See Example 210 359 4-Dimethylamino Isopropoxy Toluene: Heptane 51 See Example 210 360 4-Dimethylamino phenethyl NA 45 See Example 210 361 4-Dimethylamino Cyclopropyl ethanol 77 See Example 210

Table 5A: Physical data of synthesized compounds of formula IX. Example Mp.(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 358 253-255 74.73 74.20 6.27 6.13 13.75 13.34 359 197-198 65.91 66.33 7.01 6.86 15.37 15.27 360 224-225 75.20 75.08 6.62 6.56 13.15 13.19 361 280-289 70.56 70.33 6.71 6.80 16.46 16.20

VI. 4-[(Pyrazol-4-yl)methylene]-2-pyrazolin-5-one (X).

Table 6: Synthetic compounds of formula X. Example Substituents on Ring A R ¹ recrystallization solvent Yield% method 362 3-methyl Isopropoxy ethyl acetate 80 See Example 210 363 3-methyl Cyclopropyl toluene 51 See Example 210

Table 6A: Physical data of synthesized compounds of formula X. Example Mp(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 362 228-230 56.39 56.06 6.02 5.91 23.91 23.77 363 265-267 61.09 61.30 5.59 5.83 25.91 25.71

VII. 4-[(Imidazol-2-yl)methylene]-2-pyrazolin-5-one (XI).

Table 7: Synthesized compounds of formula XI. Example Substituents on Ring A R ¹ recrystallization solvent Yield% method 364 none Isopropoxy Toluene 45 See Example 210 365 none Cyclopropyl ethanol 42 See Example 210

Table 7A: Physical data for synthesized compounds of formula XI. Example Mp(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 364 212-214 54.53 54.96 5.49 4.61 25.43 25.67 365 264-266 59.39 59.52 4.98 5.00 27.71 27.37

VIII. 4-[(Imidazol-4-yl)methylene]-2-pyrazolin-5-one (XII).

Table 8: Synthesized compounds of formula XII. Example Substituents on Ring A R ¹ recrystallization solvent Yield% method 366 none Isopropoxy ethanol 81 See Example 210

Table 8A: Physical data of synthesized compounds of formula XII. Example Mp(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 366 259-260 54.53 54.84 5.49 5.68 25.43 25.37

IX. 4-[(Thien-2-yl)methylene]-2-pyrazolin-5-one (XIII).

Table 9: Synthesized compounds of formula XIII. Example Substituents on Ring A R ¹ recrystallization solvent Yield% method 367 none Cyclopropyl ethanol 20 See Example 210

Table 9A: Physical data of synthesized compounds of formula XIII. Example Mp(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 367 275-277 60.53 60.68 4.61 4.74 12.83 12.50

X. 4-[(Indol-3-yl)methylene]-1-methyl-2-pyrazolin-5-one (XIV).

Table 10: Synthesized compounds of formula XIV. Example Substituents on indole R ¹ recrystallization solvent Yield% method 368 none Isopropyl ethanol 54 See Example 210

Table 10A: Physical data of synthesized compounds of formula XIV. Example Mp(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 368 241-242 71.88 71.73 6.41 6.47 15.72 15.71

XI. 4-[(Pyrrol-3-yl)methylene]-2-pyrazolin-5-one (XV).

Table 11: Synthesized compounds of formula XV. Example Substituents on pyrrole R ¹ recrystallization solvent Yield% method 369 none Isopropoxy Methanol 70 See Example 210

Table 11A: Physical data for synthesized compounds of formula XV. Example Mp(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 369 252-255 60.26 60.35 5.98 5.82 19.17 19.13

XII. 4-[(Quinolin-5-yl)methylene]-2-pyrazolin-5-one (XVI).

Table 12: Synthetic compounds of formula XVI. Example Substituents on quinoline R ¹ recrystallization solvent Yield% method 370 8-hydroxy Isopropoxy Methanol 40 See Example 210

Table 12A: Physical data of the synthesized compound of formula XVI. Example Mp(°C) Elemental analysis carbon hydrogen nitrogen Calculated measured value Calculated measured value Calculated measured value 370 >300 64.64 64.43 5.09 5.01 14.13 13.98

X. Raw material synthesis.

A. Synthesis of 3-ketoesters (XIX).

The general procedure for the synthesis of 3-ketoesters is shown in Reaction Scheme II.

Reaction Scheme II: Synthesis of 3-ketoesters

Example 371: Ethyl 3-(2,2,3,3-tetramethylcyclopropyl)-3-oxopropanoate.

To an ice-cooled solution of 2,2-dimethyl-1,3-dioxane-4,7-dione (4.7 g, 0.032 mol) in anhydrous dichloromethane (37 mL) under nitrogen atmosphere To this was added pyridine (5 g, 0.063 mol) and 2,2,3,3-tetramethylcyclopropylcarbonyl chloride (5 g, 0.031 mol). It was held at 0°C for 1 hour, then allowed to warm to room temperature overnight. The mixture was then transferred to a separatory funnel and washed twice with 3% hydrochloric acid and twice with water. The organic layer was dried over magnesium sulfate, then filtered and concentrated under reduced pressure to give 5 g of a dark red oil. The oil was refluxed in absolute ethanol (60 mL) for 3 hours. The solvent was evaporated and the product was purified by distillation.

Example 377: Ethyl 3-(6-methoxybenzothiazol-2-yl)-3-oxopropanoate.

To sodium hydride (1.5 g, 50% dispersion in oil, 0.032 mol) was added ethyl acetate (7.2 g, 0.082 mol) keeping the temperature below 25°C. 2-Ethoxycarbonyl-2-(6-methoxy)benzothiazole (5.25 g, 0.022 mol) was added. The mixture was warmed to gentle reflux, then stirred at room temperature overnight. The reaction was quenched with ice water (50 mL) and adjusted to pH 7.7 with concentrated hydrochloric acid. The product precipitated and was collected by filtration, washed with water, and dried.

Example 378: Ethyl 4-(4-phenylphenoxy)-3-oxobutanoate.

To 75 mL of dimethylformamide (hereinafter referred to as "DMF") were added sodium hydride (5.0 g, 0.114 mol) and 4-phenylphenol (15.3 g, 0.09 mol) at 0°C over 2 hours. Ethyl 4-chloroacetoacetate (5.0 g, 0.03 mol) in DMF (75 mL) was added. The mixture was stirred at 0°C for 1 hour and at room temperature for 12 hours, then neutralized with 50% phosphoric acid and extracted with dichloromethane. The product was purified by silica gel chromatography using (8:2) toluene:ethanol as mobile phase.

Table 13: Synthesized compounds of formula XIX. Example R ¹ Yield% bp(°C) mp(°C) method 371 2,2,3,3-Tetramethylcyclopropyl 67 68(0.2mmHg) NA See Example 371 372 2-methylcyclopropyl 50 62-4 (0.2mmHg) NA See Example 371 373 trans-2-phenylcyclopropyl 64 138-40 (0.2mmHg) NA See Example 371 374 Tetrahydrofuran-3-yl 60 82-6 (0.2mmHg) NA See Example 371 375 3-methoxybenzyl 62 132(0.2mmHg) NA See Example 371 376 phenethyl 55 110(0.2mmHg) NA See Example 371 377 6-methoxybenzothiazol-2-yl 65 NA 160 See Example 377 378 4-Phenylphenoxymethyl 33 NA 83 See Example 378 379 3-Chlorophenoxymethyl 32 147(8mmHg) NA See Example 378 380 pyrazinyl 71 NA 82 See Example 377

B. Synthesis of ethyl cyclopentyloxythiocarbonyl acetate.

Reaction Scheme III: Synthesis of ethyl alkoxy or aryloxy iminocarboacetate hydrochloride (R ⁹ is a substituted or unsubstituted aliphatic or aromatic group).

Example 381: Synthesis of ethyl cyclopentyloxyiminocarboacetate hydrochloride (XXII).

A mixture of anhydrous ethyl cyanoacetate (14 g, 0.12 mol) and anhydrous cyclopentanol (12 g, 0.15 mol) was saturated with hydrogen chloride gas at 0°C for 3 hours, kept at 0°C overnight, and then diluted with diethyl ether. The product precipitated , collected by filtration and washed with ether.

Yield 22.4 g, (77%), melting point 110-112°C

Reaction Scheme IV: Synthesis of ethyl alkoxythio or aryloxythiocarbonyl acetates.

Example 382: Ethyl cyclopentyloxythiocarbonyl acetate (XXIV)

A mixture of ethyl cyclopentyloxyiminocarbonyl acetate hydrochloride (22 g 0.09 mol) in anhydrous pyridine (150 ml) was treated with hydrogen sulfide for 8 hours and kept at room temperature for 48 hours. The reaction mixture was acidified with concentrated hydrochloric acid and extracted with ether. The ether phase is washed with water, dried and purified by distillation.

Yield 15g, (75%), melting point 140-142°C (15mm Hg).

C. Synthesis of 2-pyrazolin-5-one

2-Pyrazolin-5-one was synthesized by the following four methods.

Reaction Scheme V: Method 1 for the synthesis of 2-pyrazolin-5-ones.

Reaction Scheme VI: Method 2 for the synthesis of 2-pyrazolin-5-ones.

Reaction Scheme VII: Method 3 for the synthesis of 2-pyrazolin-5-ones.

Reaction Scheme VIII: Method 4 for the synthesis of 2-pyrazolin-5-ones.

Example 383: 3-(2,2,3,3-Tetramethylcyclopropyl)-2-pyrazolin-5-one.

Add hydrazine hydrate (1.1 g, 0.024 mol). The reaction mixture was refluxed for 3 hours. After cooling, the solvent was evaporated and the residue was triturated with hexane to give a white solid.

Example 411: 3-(4-Hydroxybenzyl)-2-pyrazolin-5-one

A stirred suspension of 3-(4-methoxybenzyl)-2-pyrazolin-5-one (2.5 mmol) in 100 ml of dichloromethane was cooled at -78°C, and 7.5 ml of tribrominated Boron (1M solution in dichloromethane) was treated. After 1 hour at -78°C, the reaction mixture was stirred at room temperature for 12 hours. The mixture was quenched with 50 ml of water. The aqueous phase was separated and basified with 5% sodium bicarbonate solution. The formed precipitate was filtered and crystallized from methanol.

Example 413: 3-(4-Carbamoylphenethyl)-2-pyrazolin-5-one

A mixture of 3-(4-methoxycarbonylphenethyl)-2-pyrazolin-5-one (7.7 mmol) in 25% ammonium hydroxide (30 ml) was stirred at room temperature for 12 hours. The solvent was concentrated in vacuo and the solid product formed was filtered and dried.

Example 414: 3-(2-Aminocarbonylethyl)-2-pyrazolin-5-one

A mixture of 3-(ethoxycarbonylmethyl)-2-pyrazolin-5-one (1 g, 5.8 mmol) and NaCN (28 mg, 0.58 mmol) in 30 ml of 9M ammonia in methanol was placed in a sealed tube at 45 °C for 3 days. After cooling, the solvent was evaporated and the residue was suspended in water. The precipitated solid was collected by filtration.

Example 416: 3-(4-Methoxyanilino)-2-pyrazolin-5-one

A mixture of 3-amino-2-pyrazolin-5-one (20 mmol), 4-methoxyaniline (25 mol) in 50 ml acetic acid was refluxed for 4 hours. The solvent was evaporated and the residue was suspended in water. The solid was filtered and crystallized from methanol.

Table 14: Synthesized compounds of formula XXVI. Example R ¹ Yield% Mp(°C) recrystallization solvent method 383 2,2,3,3-Tetramethylcyclopropyl 44 195-7 NA See Example 383 384 Ethoxycarbonylmethyl 44 115-6 toluene See Example 383 385 pyrrol-2-yl 30 205-8 NA See Example 383 386 Indol-3-yl 69 250-3 NA See Example 383 387 6-methoxybenzothiazol-2-yl 40 269-70 NA See Example 383 388 2-methylcyclopropyl 70 196-7 water See Example 383 389 trans-2-phenylcyclopropyl 65 194-5 ethanol See Example 383 390 Tetrahydrofuran-3-yl 36 204-5 ethanol See Example 383 391 4-methoxybenzyl 73 192-5 NA See Example 383 392 4-Methylbenzyl 80 212-4 ethanol: water See Example 383 393 4-chlorobenzyl 67 206-8 ethanol See Example 383 394 4-methoxybenzyl 72 163-5 NA See Example 383 395 3,4-Dimethoxybenzyl 69 193-5 NA See Example 383 396 phenethyl 72 204-7 NA See Example 383 397 2-Phenylpropyl 72 215 NA See Example 383 398 2-Phenylpropyl 76 200-1 ethanol See Example 383 399 4-methoxyphenethyl 85 230 ethanol See Example 383 400 4-Methylphenethyl 90 251-2 NA See Example 383 401 4-Chlorophenethyl 63 243 NA See Example 383 402 4-nitrophenethyl 69 247 DMF: water See Example 383 403 4-Aminophenethyl 61 220-2 NA See Example 383 404 4-Methoxycarbonylphenethyl 77 259-60 ethanol See Example 383 405 4-Phenylphenoxymethyl 50 250 ethanol See Example 383 406 4-methoxyphenoxymethyl 70 216-8 ethanol See Example 383 407 4-Chlorophenoxymethyl 38 224-6 ethanol See Example 383 408 3-Chlorophenoxymethyl 40 232-4 ethanol See Example 383 409 4-Methylphenoxymethyl 77 207-10 Methanol See Example 383 410 Cyclopentyloxy 75 180-1 Toluene See Example 383 411 4-Hydroxybenzyl 75 233 Methanol See Example 411 412 4-Hydroxyphenethyl 70 205-6 water See Example 411 413 4-carbamoylphenethyl 90 >270 DMF: water See Example 413 414 2-Aminocarbonylethyl 66 193-6 NA See Example 414 415 2-Dimethylaminocarbonylethyl 38 203-9 NA See Example 414 416 4-methoxyanilino 30 232-4 Methanol See Example 416 417 4-Chloroanilino 28 262-4 ethanol See Example 416 418 4-Fluoroanilino 35 259-60 NA See Example 416 419 Cyclopropylamino 82 155-158 NA See Example 383 420 pyrazinyl 86 193(d) ethanol See Example 383 421 Isopropylamino 20 123-25 ethanol See Example 383 422 2-pyrimidinyl 55 278-80 ethanol See Example 383 423 3-pyridazinyl 83 294-95 ethanol See Example 383 424 4-pyrimidinyl 72 290-300 ethanol See Example 383 425 4-pyrimidinyl 60 288-291 ethanol See Example 383

D. Synthetic aldehydes

Example 426: 1-(4-Acetoxybutyl)-azaindole-3-carbaldehyde

To a stirred suspension of 60% sodium hydride (oil dispersion) (1.2 g, 30 mmol) in anhydrous DMF (65 ml) was added dropwise 7-azepam under nitrogen atmosphere, keeping the temperature at 5-10 °C. A solution of indole-3-carbaldehyde (4.19 g, 28 mmol) in anhydrous N,N-dimethylformamide (50 ml). After the addition was complete, stirring was continued at the same temperature for 30 minutes, and then a solution of 4-bromobutyl acetate (6.16 g, 31 mmol) in anhydrous N, N-dimethylformamide (15 ml) was added dropwise to make the The mixture was warmed to room temperature. The reaction mixture was stirred at room temperature for 137 hours, then water (100ml) was added and the mixture was extracted with dichloromethane (2 x 100ml). The organic phase was washed with water (3 x 100ml), dried over anhydrous magnesium sulfate, filtered and the solvent removed under reduced pressure to give an oil (6.8g, 93%) which was used without further purification.

Example 427: 1-(4-Hydroxybutyl)-7-azaindole-3-carbaldehyde

To a solution of 1-(4-acetoxybutyl)-7-azaindole-3-carbaldehyde (2.3g, 8.8mmol) in methanol (40ml) was added sodium hydroxide (0.2g, 17.5mmol) Solution in water (35ml). The mixture was heated at 60°C for 0.5 hours, then the solvent was evaporated to dryness. The residue was dissolved in a mixture of ethyl acetate and water (50ml:50ml), and the aqueous layer was separated. The organic phase was washed with water, dried over magnesium sulfate, filtered and evaporated to dryness. The residue was used without further purification. Yield 78%. The melting point is 90°C.

Example 428: 1-(4-Hydroxybutyl)pyrrole-2-carbaldehyde

The product was obtained as in Example 51, except that pyrrole-2-carbaldehyde was used instead of 7-azaindole-3-carbaldehyde. The product was purified by silica gel chromatography eluting with (5:5) ethyl acetate:hexane. Yield 67%.

Example 429: 3-Isopropyl-5-methylpyrrole-2-carbaldehyde

To a solution of anhydrous DMF (2.1 ml, 27 mmol) in anhydrous dichloroethane (50 ml) was added _POCl3 (2.1 ml, 23 mmol) dropwise at 0°C under nitrogen atmosphere. The solution was warmed to room temperature for 1 hour. Then, the suspension was cooled to 0° C., and a solution of 3-isopropyl-5-methylpyrrole (2 g, 16 mmol) in dichloroethane (20 ml) was added dropwise over 20 minutes. After stirring at room temperature for 24 hours, water was added, followed by NaOH to pH:8. The organic layer was extracted, dried and stripped of solvent to dryness. The residue was purified by flash chromatography. Yield 67%, melting point 90-93°C.

Example 430: 3,5-Dimethyl-4-morpholinomethylpyrrole-2-carbaldehyde

To a solution of morpholine (0.35g, 4mmol), 37% formaldehyde (0.32g, 4mmol) and acetic acid (2ml) was added 3,5-dimethylpyrrole-2-carbaldehyde (0.5g, 4mmol). The mixture was stirred at room temperature under nitrogen overnight, then the reaction was diluted to pH8 with _NaHCO3 . The aqueous solution was extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate. Ethyl acetate was evaporated in vacuo to give 0.4 g of pure solid.

Following a method similar to that described in Example 430, the following compounds were synthesized:

3,5-Dimethyl-4-dimethylaminomethylpyrrole-2-carbaldehyde,

3-(4-morpholino)methyl-indole-2-carbaldehyde,

3,5-Dimethyl-4-diethylaminomethylpyrrole-2-carbaldehyde,

3,5-Dimethyl-4-piperidinomethylpyrrole-2-carbaldehyde,

3,5-Dimethyl-4-[(4-methyl-1-piperazinyl)methyl]pyrrole-2-carbaldehyde,

3,5-Dimethyl-4-(1-pyrrolidinylmethyl)pyrrole-2-carbaldehyde,

5-methyl-4-dimethylaminomethylpyrrole-2-carbaldehyde,

3,5-Dimethyl-4-[N-methyl-N-(2-dimethylaminoethyl)aminomethyl]pyrrole-2-carbaldehyde,

3,5-Dimethyl-4-diethanolaminomethylpyrrole-2-carbaldehyde,

4-(4-Benzylpiperidinomethyl)-3,5-dimethylpyrrole-2-carbaldehyde,

4-Dimethylaminomethyl-3-isopropyl-5-methylpyrrole-2-carbaldehyde,

3,5-Dimethyl-4-(4-hydroxypiperidinomethyl)pyrrole-2-carbaldehyde, and

3-Dimethylaminomethyl-4,5-tetramethylenepyrrole-2-carbaldehyde.

Example 431: 3,5-Dimethyl-4-trifluoroacetamidomethylpyrrole-2-carbaldehyde

Keeping the temperature below 10 °C, a mixture of 3,5-dimethylpyrrole-2-carbaldehyde (2.6 g, 0.02 mol) and N-(hydroxymethyl)trifluoroacetamide (3 g, 0.02 mol) was added in portions sulfuric acid (15ml). The reaction mixture was allowed to warm to room temperature for 4 hours, the reaction was poured into ice water (100ml), and the precipitated solid was filtered and washed with water. The resulting white solid (78% yield) was used without further purification. M.p.200°C.

Example 432: 4-Aminomethyl-3,5-dimethylpyrrole-2-carbaldehyde

A mixture of 3,5-dimethyl-4-trifluoroacetamidomethylpyrrole-2-carbaldehyde (3.9 g, 15.7 mmol), NaOH 10% (19 ml) and methanol (100 ml) was heated at reflux for 1 hour. The solution was concentrated under reduced pressure to half volume. Water was added and the precipitated solid was filtered. Yield 72%, m.p. 210-20°C (d).

Example 433: 3-Acetyl-4-oxopentyl acetate

Under mechanical stirring, pentane-2,4-dione (60g, 0.6mol), 2-bromoethyl acetate (100g, 0.6mol), anhydrous potassium carbonate (83g, 0.6mol), IK (99.6g , 0.6mol) and a mixture of anhydrous acetone (500ml) was heated to reflux for 24 hours. The mixture was concentrated under reduced pressure and poured into hydrochloric acid (1.7M, 400ml). The product was isolated by successive extractions with ether, ethyl acetate and dichloromethane. The combined organic extracts were washed with brine, the solvent was removed to dryness, and the residue was distilled to give 38 g of the acetate salt, b.p. 75-80°C (0.1 mm Hg).

Following a procedure similar to that described in Example 433, 4-acetyl-5-oxohexyl acetate [60% yield, b.p. 110°C (0.2mm Hg)] and 5-acetyl-6-oxoacetate Hexyl ester [77% yield, b.p. 102°C (0.2 mm Hg)].

Example 434: tert-Butyl 4-(2-acetoxyethyl)-3,5-dimethylpyrrole-2-carboxylate

To a solution of tert-butyl acetoacetate (26g, 0.165mol) in acetic acid (48ml) was added dropwise sodium nitrite (11.3g, 0.165mol) in water (17ml) at a temperature below 20°C under stirring. solution and left overnight. A solution of 3-acetyl-4-oxopentyl acetate (30 g, 0.161 mol) in acetic acid (56 ml) was heated to 80° C., at which point zinc powder (26.2 g, 0.40 mol) and sodium acetate were added in portions (26.3 g, 0.32 mol) of the mixture, while the above hydroxyimino derivative (97 ml, 0.165 mol) was added dropwise. The reaction mixture was stirred vigorously during the addition so that there was always an excess of zinc and the temperature was maintained at 90-100°C. When the addition was complete, the mixture was boiled gently for 15 minutes and stirred at room temperature overnight. The reaction mixture was poured into ice water and left for 2hr. The solid was filtered and recrystallized from aqueous ethanol. Yield 78%, melting point 92°C.

Following a procedure similar to that described in Example 434, tert-butyl 4-(3-acetoxypropyl)-3,5-dimethylpyrrole-2-carboxylate was prepared [yield 60%, m.p. 73°C (hexane )] and tert-butyl 4-(4-acetoxybutyl)-3,5-dimethylpyrrole-2-carboxylate [52% yield, m.p. 62°C (hexane)].

Example 435: 3,5-Dimethyl-4-(2-hydroxyethyl)pyrrole-2-carbaldehyde.

Dissolve tert-butyl 4-(2-acetoxyethyl)-3,5-dimethylpyrrole-2-carboxylate (15 g, 53 mmol) in TFA (40 ml) and stir at 40 °C under nitrogen atmosphere The solution was left for 10 minutes. The reaction mixture was then cooled to 0°C and triethylorthoformate (9.6ml, 58mmol) was added dropwise. The mixture was warmed to 20°C and stirred for 1 hour, then poured into ice water. After extraction with dichloromethane, the extract was washed successively with 10% ammonia and water, and dried over magnesium sulfate. 4-(2-Acetoxyethyl)-3,5-dimethylpyrrole-2-carbaldehyde was purified by silica gel chromatography eluting with (7:3) ethyl acetate:hexane. Yield 45%, m.p. 125-27°C (water).

To a solution of the above compound (5 g, 23 mmol) in ethanol (20 ml) was added NaOH 10% (10 ml). The mixture was stirred at room temperature for 30 minutes, and the final solution was concentrated, diluted with water, and extracted with dichloromethane. The organic extract was dried and the solvent removed to dryness. Yield 98%, m.p. 100°C (ethyl acetate).

Following a procedure similar to that described in Example 435, 3,5-dimethyl-4-(3-hydroxypropyl)pyrrole-2-carbaldehyde was prepared [60% yield, m.p. 85°C (ethyl acetate/hexane )] and 3,5-dimethyl-4-(4-hydroxybutyl)pyrrole-2-carbaldehyde [38% yield, m.p. 99°C (hexane)].

Example 436: 4-(2-Diethylaminoethyl)-3,5-dimethylpyrrole-2-carbaldehyde.

At 0-5°C, 3,5-dimethyl-4-(2-hydroxyethyl)pyrrole-2-carbaldehyde (4.3g, 25.7mmol) and triethylamine (5.2g, 51mmol) were stirred in the absence of To a solution in aqueous THF (60ml) was added methanesulfonyl chloride (4ml, 51mmol) in anhydrous THF (4ml) and the mixture was stirred at room temperature for 1 hour. Water was then added to the mixture, and the precipitated solid was filtered. Yield 89%, m.p. 142-44°C.

A mixture of the above mesylate (23mmol), _K2CO3 (23mmol), _diethylamine (90mmol) and 2-propanol (70ml) was heated to 100°C for 0.5h. The solvent was removed to dryness and the residue was treated with water and extracted with dichloromethane. The organic extract was dried, and the solvent was evaporated to dryness. Yield 70%, mp 70°C (n-heptane).

3,5-Dimethyl-4-[2-(1-pyrrolidinylethyl)]pyrrole-2-carbaldehyde, 3,5-dimethyl-4-[2-(1-pyrrolidinylethyl)]pyrrole-2-carbaldehyde, 3,5 -Dimethyl-4-(2-ethylaminoethyl)pyrrole-2-carbaldehyde, 4-(3-diethylaminopropyl)-3,5-dimethylpyrrole-2-carbaldehyde, 4-(4 -diethylaminobutyl)-3,5-dimethylpyrrole-2-carbaldehyde, 3,5-dimethyl-4-[3-(1-pyrrolidinylpropyl)]pyrrole-2-carbaldehyde.

Example 437: 4-(2-Chloroacetyl)-3,5-dimethylpyrrole-2-carbaldehyde

To a solution of 3,5-dimethylpyrrole-2-carbaldehyde (5 g, 40 mmol) in 1,2-dichloroethane (50 mL) was added portionwise anhydrous Aluminum chloride (42 g, 315 mmol). After stirring for 15 minutes, chloroacetyl chloride (17 g, 150 mmol) was added dropwise over 1 hour. After the addition was complete, the mixture was stirred at room temperature for 16 hours. The mixture was poured into crushed ice, the organic layer was separated, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Yield 57%, m.p. 205-09°C (toluene).

Example 438: 3,5-Dimethyl-4-(2-diethylaminoacetyl)pyrrole-2-carbaldehyde

To a solution of 4-(2-chloroacetyl)-3,5-dimethylpyrrole-2-carbaldehyde (1 g, 5 mmol) in THF (20 ml) was added diethylamine (5 ml). The mixture was stirred at room temperature for 24 hours. The solvent was removed under reduced pressure and the residue was treated with water, _NaHCO3 (5%) and extracted with dichloromethane. After drying and filtration, the solvent was removed and the residue was used without further purification.

Following a method similar to that described in Example 438, 3,5-dimethyl-4-(2-dimethylaminoacetyl)pyrrole-2-carbaldehyde and 3,5-dimethyl-4-[2- (1-Pyrrolidinyl)acetyl]pyrrole-2-carbaldehyde.

Example 439: 3,5-Dimethyl-4-ethoxyoxalylpyrrole-2-carbaldehyde

To a solution of 3,5-dimethylpyrrole-2-carbaldehyde (7.6 g, 62 mmol) in 1,2-dichloroethane (140 ml) was added portion-wise at room temperature under a nitrogen atmosphere over 30 minutes without Aluminum chloride hydrate (37 g, 277 mmol). After stirring for 30 minutes, nitromethane (11.2ml, 179mmol) was added. The mixture was cooled at 0°C, and ethyl chloroglyoxylate (12.8 g, 94 mmol) was added dropwise over 1 hour. After the addition was complete, the mixture was stirred at room temperature for 4 hours. The mixture was poured into crushed ice and the organic layer was separated, dried and evaporated to give a white solid. Yield 45%, m.p. 125-127°C (toluene).

The NMR spectrum data of all the compounds in the previous examples are consistent with the corresponding chemical structures.

Although the present invention has been described in detail with reference to its preferred embodiments, it will be understood by those skilled in the art that many changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the claims.

Claims (34)

1. compound shown in the following formula and physiologically acceptable salt thereof are used for suppressing the application of the medicine of one or more protein kinase activities in preparation:

Wherein:

R is selected from replacement or unsubstituted: C ₃-C ₆Cycloalkyl, quinolyl, thienyl, imidazolyl, pyrryl, indyl, pyrrolo-pyrimidine radicals, phenyl, azaindole base and pyrazolyl;

R ¹Be hydrogen or-A-Z;

R ²Be that hydrogen or be selected from replaces or unsubstituted C ₁-C ₆Groups;

A is-(CH ₂) _n-,-(CH ₂) _nNH-or-(CH ₂) _nO-;

Z is-H, C ₁-C ₆Alkyl, R ³OC (O)-,-NR ⁴R ⁵,-C (O) NR ⁴R ⁵, R ³O-or be selected from following one group ring system: (C ₃-C ₆) cycloalkyl, benzene, pyrroles, isoxazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, furans and pyridazine, wherein said ring system is unsubstituted or is selected from following one group group and replaces by one or more: halogen, C ₁-C ₆Alkyl, R ³O-, HO-, R ³OC (O)-, nitro, phenyl and-NR ⁴R ⁵

The R that every place occurs ³Be independently from each other replacement or unsubstituted: C ₁-C ₆Groups, phenyl group, phenmethyl group and (C ₃-C ₆) naphthene group;

The R that every place occurs ⁴And R ⁵Independently of one another for hydrogen or be selected from and replace or unsubstituted: C ₁-C ₆Groups, phenyl group and (C ₃-C ₆) naphthene group; And

N is the integer of 0-3; Condition is that this compound is not 3H-pyrazoles-3-ketone, 2, and 4-dihydro-4-[[4-hydroxyl-3, two (1-methylethyl) phenyl of 5-] methylene radical]-the 5-methyl.

2. the application of claim 1, compound wherein are the mixture of steric isomer.

3. the application of claim 2, steric isomer wherein is an enantiomorph.

4. the application of claim 2, steric isomer wherein are E and Z isomer.

5. the application of claim 1, compound wherein are the mixtures of constitutional isomer.

6. the application of claim 5, constitutional isomer wherein is a tautomer.

7. the application of claim 1, wherein said protein kinase are receptor tyrosine kinase or nonreceptor tyrosine kinase.

8. the application of claim 7, wherein said Tyrosylprotein kinase is selected from and contains kinases insertion domain receptor, fms sample Tyrosylprotein kinase-1, TIE-2, fibroblast growth factor acceptor, platelet derived growth factor receptor, IGF-1R, the met proto-oncogene, lymph T cell kinase, the cell homologue of Rous sarcoma virus oncoprotein, fgr and yes related protein are present in hemopoietic tissue and the brain, the related protein of the cell homologue of tumor virus oncoprotein in the cell homologue of Gardner-Rasheed sarcoma virus oncoprotein and the Yamaguchi73, lymph B cell kinase), the cell homologue of Yamaguchi73 sarcoma virus oncoprotein.

9. the application of claim 1, wherein said protein kinase is a serine kinase.

10. the application of claim 1, wherein said protein kinase is a threonine kinase.

11. compound shown in the following formula and physiologically acceptable salt thereof are used for the treatment of or fundamentally suppress need application in the medicine of curer's inflammatory diseases in preparation:

Wherein:

R is selected from replacement or unsubstituted: C ₃-C ₆Cycloalkyl, quinolyl, thienyl, imidazolyl, pyrryl, indyl, pyrrolo-pyrimidine radicals, phenyl, azaindole base and pyrazolyl;

R ¹Be hydrogen or-A-Z;

R ²Be that hydrogen or be selected from replaces or unsubstituted C ₁-C ₆Groups;

A is-(CH ₂) _n-,-(CH ₂) _nNH-or-(CH ₂) _nO-;

Z is-H, C ₁-C ₆Alkyl, R ³OC (O)-,-NR ⁴R ⁵,-C (O) NR ⁴R ⁵, R ³O-or be selected from following one group ring system: (C ₃-C ₆) cycloalkyl, benzene, pyrroles, isoxazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, furans and pyridazine, wherein said ring system is unsubstituted or is selected from following one group group and replaces by one or more: halogen, C ₁-C ₆Alkyl, R ³O-, HO-, R ³OC (O)-, nitro, phenyl and-NR ⁴R ⁵

The R that every place occurs ³Be independently from each other replacement or unsubstituted: C ₁-C ₆Groups, phenyl group, phenmethyl group and (C ₃-C ₆) naphthene group;

The R that every place occurs ⁴And R ⁵Independently of one another for hydrogen or be selected from and replace or unsubstituted: C ₁-C ₆Groups, phenyl group and (C ₃-C ₆) naphthene group; And

N is the integer of 0-3.

12. compound shown in the following formula and physiologically acceptable salt thereof are used for the treatment of or suppress to need application in the medicine of curer's vasculogenesis in preparation:

Wherein:

R is selected from replacement or unsubstituted: C ₃-C ₆Cycloalkyl, quinolyl, thienyl, imidazolyl, pyrryl, indyl, pyrrolo-pyrimidine radicals, phenyl, azaindole base and pyrazolyl;

R ¹Be hydrogen or-A-Z;

R ²Be that hydrogen or be selected from replaces or unsubstituted C ₁-C ₆Groups;

A is-(CH ₂) _n-,-(CH ₂) _nNH-or-(CH ₂) _nO-;

Z is-H, C ₁-C ₆Alkyl, R ³OC (O)-,-NR ⁴R ⁵,-C (O) NR ⁴R ⁵, R ³O-or be selected from following one group ring system: (C ₃-C ₆) cycloalkyl, benzene, pyrroles, isoxazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, furans and pyridazine, wherein said ring system is unsubstituted or is selected from following one group group and replaces by one or more: halogen, C ₁-C ₆Alkyl, R ³O-, HO-, R ³OC (O)-, nitro, phenyl and-NR ⁴R ⁵

The R that every place occurs ³Be independently from each other replacement or unsubstituted: C ₁-C ₆Groups, phenyl group, phenmethyl group and (C ₃-C ₆) naphthene group;

The R that every place occurs ⁴And R ⁵Independently of one another for hydrogen or be selected from and replace or unsubstituted: C ₁-C ₆Groups, phenyl group and (C ₃-C ₆) naphthene group; And

N is the integer of 0-3.

13. compound shown in the following formula and physiologically acceptable salt thereof are used for inducing the application of the medicine that needs curer's blood vessel formation against function in preparation:

Wherein:

R is selected from replacement or unsubstituted: C ₃-C ₆Cycloalkyl, quinolyl, thienyl, imidazolyl, pyrryl, indyl, pyrrolo-pyrimidine radicals, phenyl, azaindole base and pyrazolyl;

R ¹Be hydrogen or-A-Z;

R ²Be that hydrogen or be selected from replaces or unsubstituted C ₁-C ₆Groups;

A is-(CH ₂) _n-,-(CH ₂) _nNH-or-(CH ₂) _nO-;

Z is-H, C ₁-C ₆Alkyl, R ³OC (O)-,-NR ⁴R ⁵,-C (O) NR ⁴R ⁵, R ³O-or be selected from following one group ring system: (C ₃-C ₆) cycloalkyl, benzene, pyrroles, isoxazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, furans and pyridazine, wherein said ring system is unsubstituted or is selected from following one group group and replaces by one or more: halogen, C ₁-C ₆Alkyl, R ³O-, HO-, R ³OC (O)-, nitro, phenyl and-NR ⁴R ⁵

The R that every place occurs ³Be independently from each other replacement or unsubstituted: C ₁-C ₆Groups, phenyl group, phenmethyl group and (C ₃-C ₆) naphthene group;

The R that every place occurs ⁴And R ⁵Independently of one another for hydrogen or be selected from and replace or unsubstituted: C ₁-C ₆Groups, phenyl group and (C ₃-C ₆) naphthene group; And

N is the integer of 0-3.

14. compound shown in the following formula and physiologically acceptable salt thereof are used for the treatment of or suppress to need application in the medicine of curer's disease or illness in preparation:

Wherein:

R is selected from replacement or unsubstituted: aromatic group, (C ₃-C ₆) cycloalkyl, heterocyclic radical, aralkyl, (C ₃-C ₆) cycloalkyl-alkyl and heterocyclic radical-alkyl;

R ¹Be hydrogen or-A-Z;

R ²Be that hydrogen or be selected from replaces or unsubstituted: C ₁-C ₆Alkyl, aromatic group, (C ₃-C ₆) cycloalkyl, heterocyclic radical, aralkyl, (C ₃-C ₆) cycloalkyl-alkyl, heterocyclic radical-alkyl;

A is-(CH ₂) _n-,-(CH ₂) _nNH-,-(CH ₂) _nO-,-(CH ₂) _nS-,-(CH ₂) _nS (O)-or-(CH ₂) _nS (O) ₂-;

Z is-H, C ₁-C ₆Alkyl, aralkyl, R ³CO-, R ³OC (O)-,-NR ⁴R ⁵,-C (O) NR ⁴R ⁵, R ³O-or be selected from following one group ring system: (C ₃-C ₆) cycloalkyl, benzene, pyrroles, isoxazole, isothiazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, triazine, imidazoles, furans, benzoglyoxaline, pyridazine, quinoxaline, pyrazoles, oxazole, thiazole and N-oxide compound thereof, wherein said ring system is unsubstituted or is selected from following one group group and replaces by one or more: halogen, C ₁-C ₆Alkyl, R ³O-, HO-, HOC (O)-, R ³OC (O)-, trihalomethyl group, nitro, aryl ,-CN ,-C (O) NR ⁴R ⁵With-NR ⁴R ⁵

The R that every place occurs ³Be independently from each other replacement or unsubstituted: C ₁-C ₆Alkyl, C ₁-C ₆Alkoxy C ₁-C ₆Alkyl, aromatic group, (C ₃-C ₆) cycloalkyl, heterocyclic radical, aralkyl, (C ₃-C ₆) cycloalkyl-alkyl and heterocyclic radical-alkyl;

The R that every place occurs ⁴And R ⁵Independently of one another for hydrogen or be selected from and replace or unsubstituted: C ₁-C ₆Alkyl, aromatic group, (C ₃-C ₆) cycloalkyl, heterocyclic radical, aralkyl, (C ₃-C ₆) cycloalkyl-alkyl and heterocyclic radical-alkyl; And

N is the integer of 0-3,

Wherein said disease or illness are selected from cancer, sacroiliitis, atherosclerosis, restenosis, psoriasis, vascular tumor, angiogenesis of cardiac muscle, crown and brain pleurapophysis, the ischemic limb vessel generates, keratopathy, flush, neovascular glaucoma, macular degeneration, wound healing, peptide ulceration, with the helicobacter diseases associated, the vasculogenesis disease that virus causes, fracture, diabetic retinopathy, Crohn disease, the fever that inflammatory bowel disease, cat scratcs cause, retinopathy or precocity, ulcer, the Tiroidina hyperplasia is burnt, wound, acute lung injury, chronic lung disease, apoplexy, polyp, tumour, synovitis, chronic and alterative inflammation, ovarian hyperstimulation syndrome, lung and cerebral edema, keloid, fibrosis, liver cirrhosis, carpal tunnel syndrome, Sepsis, adult respiratory distress syndrome, many organ dysfunction syndrome, ascites and seepage hydrops and the oedema relevant with tumour.

15. compound shown in the following formula and physiologically acceptable salt thereof are used for influencing the application that needs the too high or medicine that oedema produces of curer's vascular permeability in preparation:

Wherein:

R is selected from replacement or unsubstituted: C ₃-C ₆Cycloalkyl, quinolyl, thienyl, imidazolyl, pyrryl, indyl, pyrrolo-pyrimidine radicals, phenyl, azaindole base and pyrazolyl;

R ¹Be hydrogen or-A-Z;

R ²Be that hydrogen or be selected from replaces or unsubstituted C ₁-C ₆Groups;

A is-(CH ₂) _n-,-(CH ₂) _nNH-or-(CH ₂) _nO-;

Z is-H, C ₁-C ₆Alkyl, R ³OC (O)-,-NR ⁴R ⁵,-C (O) NR ⁴R ⁵, R ³O-or be selected from following one group ring system: (C ₃-C ₆) cycloalkyl, benzene, pyrroles, isoxazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, furans and pyridazine, wherein said ring system is unsubstituted or is selected from following one group group and replaces by one or more: halogen, C ₁-C ₆Alkyl, R ³O-, HO-, R ³OC (O)-, nitro, phenyl and-NR ⁴R ⁵

The R that every place occurs ³Be independently from each other replacement or unsubstituted: C ₁-C ₆Groups, phenyl group, phenmethyl group and (C ₃-C ₆) naphthene group;

The R that every place occurs ⁴And R ⁵Independently of one another for hydrogen or be selected from and replace or unsubstituted: C ₁-C ₆Groups, phenyl group and (C ₃-C ₆) naphthene group; And

N is the integer of 0-3.

16. the application of claim 15 wherein act as Ivy extract to what oedema produced.

17. compound that following structural is represented and physiologically acceptable salt thereof:

Wherein:

R is selected from replacement or unsubstituted: C ₃-C ₆Cycloalkyl, quinolyl, thienyl, imidazolyl, pyrryl, indyl, pyrrolo-pyrimidine radicals, phenyl, azaindole base, pyrazolyl, azaindolyl and 4,5,6,7-tetrahydro indole base;

R ¹Be hydrogen or-A-Z;

R ²Be that hydrogen or be selected from replaces or unsubstituted C ₁-C ₆Groups;

A is-(CH ₂) _n-,-(CH ₂) _nNH-or-(CH ₂) _nO-;

Z is-H, C ₁-C ₆Alkyl, R ³OC (O)-,-NR ⁴R ⁵,-C (O) NR ⁴R ⁵, R ³O-or be selected from following one group ring system: (C ₃-C ₆) cycloalkyl, benzene, pyrroles, isoxazole, indoles, pyridine, pyrazine, pyrimidine, benzothiazole, tetrahydrofuran (THF), thiophene, furans and pyridazine, wherein said ring system is unsubstituted or is selected from following one group group and replaces by one or more: halogen, C ₁-C ₆Alkyl, R ³O-, HO-, R ³OC (O)-, nitro, phenyl and-NR ⁴R ⁵

The R that every place occurs ³Be independently from each other replacement or unsubstituted: C ₁-C ₆Groups, phenyl group, phenmethyl group and (C ₃-C ₆) naphthene group;

The R that every place occurs ⁴And R ⁵Independently of one another for hydrogen or be selected from and replace or unsubstituted: C ₁-C ₆Groups, phenyl group and (C ₃-C ₆) naphthene group; And

N is the integer of 0-3; Condition be when R be unsubstituted indol-3-yl, R ¹Be not-NH ₂With condition be that this compound is not 3H-pyrazoles-3-ketone, 2,4-dihydro-4-[[4-hydroxyl-3, two (1-methylethyl) phenyl of 5-] methylene radical]-the 5-methyl,

18. the compound of claim 1, wherein:

A is-NH-or-O-; And

Z is cyclopropyl, 3-pyridyl or pyrazinyl.

19. the compound of claim 17, wherein:

A is-O-; And

Z is ethyl, n-propyl or sec.-propyl.

20. the compound of claim 17, wherein:

A is-CH ₂-; And

Z is a phenyl, and wherein said phenyl is unsubstituted or is selected from following one group group and replaces by one or more: halogen, hydroxyl ,-NR ⁴R ⁵, nitro, C ₁-C ₆Alkyl, R ³O-,-C (O) OR ⁴With-OC (O) R ⁴

21. the compound of claim 17 is selected from following one group compound:

3-cyclopropyl-4-([(3,5-dimethyl-4-(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-(3,5-two bromo-4-hydroxyl benzylidenes)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-cyclopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-{[(3,5-dimethyl-4-[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical)-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,

3-(3-pyridyl)-4{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

3-(3-pyridyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-isopropoxy-4-([3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

3-oxyethyl group-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

3-oxyethyl group-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-oxyethyl group-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-oxyethyl group-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-oxyethyl group-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

3-oxyethyl group-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

3-oxyethyl group-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

3-oxyethyl group-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-oxyethyl group-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-oxyethyl group-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-oxyethyl group-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,

3-oxyethyl group-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

3-pyrazinyl-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

3-pyrazinyl-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(1-skatole-3-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

3-pyrazinyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(imidazoles-2-yl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(imidazoles-2-yl))-the 2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(imidazoles-2-yl)-2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

3-(1-methyl cyclopropyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

3-(1-methyl cyclopropyl)-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(1-methyl cyclopropyl)-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(1-methyl cyclopropyl)-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(1-methyl cyclopropyl)-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

3-(1-methyl cyclopropyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

3-(1-methyl cyclopropyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[(pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[(indoles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(1-methyl cyclopropyl))-the 2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl cyclopropyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(1-pyrrolidyl methyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3-diethyllaminoethyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-(2-furyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-(2-furyl)-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-furyl)-4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-furyl)-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-furyl)-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-furyl)-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-furyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-furyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-furyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(3-(2-furyl))-2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-[(morpholino methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(4-methyl isophthalic acid-piperazinyl) methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3-(4-methyl isophthalic acid-piperazinyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3-(1-pyrrolidyl methyl)-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-oxo-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

3-(2-thienyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(1-skatole-3-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(indoles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,

3-encircles propoxy--4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-ring propoxy--4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-ring propoxy--4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-ring propoxy--4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-ring propoxy--4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-ring propoxy--4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-ring propoxy--4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-ring propoxy--4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-ring propoxy--4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-encircles propoxy--4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-encircles propoxy--4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-encircles propoxy--2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-encircles propoxy--2-pyrazolin-5-one,

3-encircles propoxy--4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-encircles propoxy--2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

3-[2-(5-pyrimidinylethyl)]-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[(1-skatole-3-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

3-[2-(5-pyrimidinylethyl)]-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

3-[2-(5-pyrimidinylethyl)]-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(indoles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(5-pyrimidinylethyl)]-the 2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

3-(2-styroyl)-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[(1-skatole-3-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

3-(2-styroyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-(2-styroyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[(indoles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-(2-styroyl)-2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-(2-styroyl)-2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-styroyl)-2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

3-[2-(4-hydroxyphenyl) ethyl]-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

3-[2-(4-hydroxyphenyl) ethyl]-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-hydroxyphenyl) ethyl]-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-hydroxyphenyl) ethyl]-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-hydroxyphenyl) ethyl]-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

3-[2-(4-hydroxyphenyl) ethyl]-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-hydroxyphenyl) ethyl]-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-3-[2-(4-hydroxyphenyl) ethyl]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(4-bromine pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(4-chlorine pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(5-chlorine pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(5-trifluoromethyl pyrpole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[4-(2-dimethylamino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[4-(2-dimethylamino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(3-ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[3-(2-dimethylamino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[3-(2-dimethylamino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[4-(4-morpholino ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[4-(4-morpholino B aminocarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[3-(4-morpholino ethoxycarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[3-(4-morpholino B aminocarbonyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(3,4-diethoxy carbonyl pyrrolidine-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3-(2-acetylaminohydroxyphenylarsonic acid 2-methoxycarbonyl ethyl) indoles-2-yl] methylene radical }-3-[2-(4-aminophenyl) ethyl]-the 2-pyrazolin-5-one,

4-{[3-(2-amino-2-propyloic) indoles-2-yl] methylene radical }-3-[2-(4-aminophenyl) ethyl]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(5-oxyethyl group-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-[2-(4-aminophenyl) ethyl]-4-[(5-chloro-4-methoxycarbonyl methyl-3-methoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

3-(4-pyrimidyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyrimidyl) pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-diethylin methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

3-(5-pyrimidyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

3-(2-pyrimidyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

3-(3-pyridazinyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(piperidino-(1-position only) methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

3-(4-pyridazinyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

3-(5-isoxazolyl)-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

3-(5-isoxazolyl)-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-(5-isoxazolyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-(5-isoxazolyl)-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-{[(4-methyl isophthalic acid-piperazinyl methyl) pyrroles-2-yl] methylene radical }-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-[(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-[(4-diethanolamine ylmethyl-3,5-dimethyl-pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

3-(5-methyl-3-isoxazolyl)-4-[(3-morpholino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3-diethylin methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

3-(5-methyl-3-isoxazolyl)-4-{[3-(4-methyl isophthalic acid-piperazinyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-(5-methyl-3-isoxazolyl)-4-{[3-(1-pyrrolidyl) methyl-4,5-tetramethylene pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-(5-methyl-3-isoxazolyl)-4-[(3-piperidino-(1-position only) methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-dimethylamino-4,5,6,7-tetrahydro indole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-[(4-diethyllaminoethyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-(3,5-two bromo-4-hydroxyl benzylidenes)-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

3-(5-methyl-3-isoxazolyl)-4-[(4-oxo-1,5,6,7-tetrahydro indole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-dimethylamino methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-(1-3-[(dimethylamino) methyl]-4,5,6,7-tetrahydrochysene-1H-2-indyl methylene radical)-4,5-dihydro-1H-5-pyrazolone,

3-cyclopropyl-4-(1-4-[(1,1-Dimethyl Ammonium) methyl]-3,5-dimethyl-1H-2-pyrryl methylene radical)-4,5-dihydro-1H-5-pyrazolone maleate,

4-[1-(4-[[2-(dimethylamino) ethyl] (methyl) amino] methyl-3,5-dimethyl-1H-2-pyrryl) methylene radical]-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,

4-(1-4-[2-(diethylin) ethyl]-3,5-dimethyl-1H-2-pyrryl methylene radical)-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,

4-1-[4-(3-chlorine propionyl)-3,5-dimethyl-1H-2-pyrryl] methylene radical-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,

4-(1-3-[(dimethylamino) methyl]-4,5,6,7-tetrahydrochysene-1H-2-indyl methylene radical)-3-(2-pyrazinyl)-4,5-dihydro-1H-5-pyrazolone,

4-(1-4-[(dimethylamino) methyl]-3,5-dimethyl-1H-2-pyrryl methylene radical)-3-(5-methyl-3-isoxazolyl)-4,5-dihydro-1H-5-pyrazolone,

3-cyclopropyl-4-[(4,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-benzyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-methoxyl group phenoxymethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-phenoxymethyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-chlorophenoxy methyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-methoxy-benzyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-benzyl-4-{[4-(2-propyloic)-3-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-benzyl-4-{[3-(2-propyloic)-4-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-(4-methylenedioxy phenoxy ylmethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

2-amino-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-styroyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-phenylamino-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-xylyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-methylbenzene amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-anisole amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-benzyl chloride base)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-chlorobenzene amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(3-chlorophenoxy methyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(indol-3-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(3-methoxy-benzyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(3, the 4-dimethoxy-benzyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-anisole ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-phenyl phenoxymethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-phenyl propyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(3-phenyl propyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-leptodactyline)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,

3-(4-methylbenzene ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-oxyethyl group-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-oil of mirbane ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-fluoroanilino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-chlorobenzene ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,

3-cyclopentyloxy-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-tertiary butyl urea groups-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-amino-benzene ethyl)-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(1-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-amino-benzene ethyl)-4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-oxyethyl group-4-[(5-methylpyrrole-2-yl) methylene radical] the 2-pyrazolin-5-one,

3-(4-formamyl styroyl)-4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(4-methoxycarbonyl styroyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-(4-amino-benzene ethyl)-4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(5-N-ethyl pyrrole N--2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(4-leptodactyline)-2-pyrazolin-5-one,

3-(ethoxycarbonylmethyl group)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(the amino carbonyl methyl of 4-anisole)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{ (3-(2-propyloic)-4-methylpyrrole-2-yl] methylene radical }-3-sec.-propyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclobutyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(3-pyridyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[[1-(3, the 5-dichlorophenyl) pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(pyrroles-2-yl) methylene radical]-3-(2,2,3,3-tetramethyl-ring propyl group)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopentyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-methyl cyclopropyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-(benzothiazole-2-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4,5-dimethyl pyrrole-2-yl) methylene radical]-4-(3-pyridyl)]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(pyrroles-2-yl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(benzothiazole-2-yl)-4-[(4-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-N-ethyl pyrrole N--2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(5-phenylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-propyl group-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-methyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-isopropyl benzene amino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(3-phenylamino)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[1-(4-hydroxybutyl) pyrroles-2-yl] methylene radical]-the 2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3-methylpyrrole-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(4-ethanoyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,

4-[(5-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(5-carboxy pyrrole-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-(4-chlorobenzene amino carbonyl methyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-phenylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(tetrahydrofuran (THF)-3-yl)-2-pyrazolin-5-one,

4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,4-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3-methylpyrrole-2-yl] methylene radical }-3-cyclopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-methoxycarbonyl ethyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-ethoxycarbonyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-sec.-propyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(anti--the 2-phenycyclopropyl)-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclohexyl-4-[(pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropylamino-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-morpholino methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(5-carboxy pyrrole-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,

4-[(4-chlorine pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(5-chlorine pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4 [(4-chlorine pyrroles-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-ones,

4-[(4-bromine pyrroles-2-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,

3-pyrazinyl-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(3-pyridyl)-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino ethoxycarbonyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one maleate,

4-{[3,5-dimethyl-4-(2-morpholino B aminocarbonyl) pyrroles-2-yl] methylene radical-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,

4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-trifluoroacetamido methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-amino methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(benzothiazole-2-yl)-4-[(3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(benzothiazole-2-yl)-4-[(3,5-dimethyl-4-morpholino methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-carboxy pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-diethanolamino methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-trifluoroacetamido methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-ethoxycarbonyl-3-phenylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(1-pyrrolidyl methyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-N-ethyl pyrrole N--2-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,

4-[(3,4-two (ethoxycarbonyl) pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

3-oxyethyl group-4-[(4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(2-pyridyl ethyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(1-methyl-2-styroyl)-2-pyrazolin-5-one,

4-[(4-carboxyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

3-oxyethyl group-4-[(5-nitro-pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-oxyethyl group-4-[(4-nitro-pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(4-carboxy pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylamino B aminocarbonyl) pyrroles-2-yl) methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,

4-[(5-chloro-3-methoxycarbonyl-4-methoxycarbonyl methylpyrrole-2-yl) methylene radical-3-oxyethyl group-2-pyrazolin-5-one,

4-{[3-(2-carboxy ethyl)-4-methylpyrrole-2-yl) methylene radical }-3-oxyethyl group-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

3-oxyethyl group-4-[(4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-trifluoromethyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

3-(3-aminophenyl)-4-[(3,5-dimethyl-4-ethoxycarbonyl pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-oxyethyl group-4-{[2-(4-morpholino ethyl) aminocarboxyl pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(4-ethoxycarbonyl-3-phenylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(4-methyl isophthalic acid-piperazinyl methyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-piperidine subbase methylpyrrole-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-isoxazolyl)-2-pyrazolin-5-one,

4-[(5-methyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[N-(2-dimethylaminoethyl)-N-methylamino-methylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(3-dimethylamino methyl-4,5-tetramethylene pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-2-pyrazolin-5-one maleate,

4-{[4-(3-chlorine propionyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino methyl pyrroles-2-yl) methylene radical]-3-(5-methyl-3-isoxazolyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(4-hydroxy piperidine subbase methyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-amino methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one maleate,

4-{[4-(4-benzyl piepridine subbase) methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-hydroxyethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-{{3,5-dimethyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[3,5-dimethyl-4-(2-hydroxyethyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-ethylamino ethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(3-diethylin propyl group)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(3-hydroxypropyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-dimethylamino acetyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one hydrochloride,

4-[(3,5-dimethyl-4-dimethylamino acetyl pyrrole-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

3-cyclopropyl-4-{[(2-diethyllaminoethyl)-3,5-dimethyl-4-pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-dimethylaminoethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(4-hydroxybutyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(4-diethylin butyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl-N-oxide compound)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(1-pyrrolidyl ethanoyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-diethylin ethanoyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-[3-(1-pyrrolidyl propyl group)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(dimethylamino methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(dimethylamino methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-oxyethyl group oxalyl group) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

3-benzyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-benzyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-methoxyl group phenoxymethyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-phenoxymethyl-2-pyrazolin-5-one,

3-(4-chlorophenoxy methyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-methoxy-benzyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-methylenedioxy phenoxy ylmethyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-xylyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-phenylamino-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-methylbenzene amino)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-anisole amino)-2-pyrazolin-5-one,

3-(4-benzyl chloride base)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-(4-methoxy-benzyl)-2-pyrazolin-5-one,

3-(4-chlorobenzene amino)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(3-methoxy-benzyl)-2-pyrazolin-5-one,

3-(3, the 4-dimethoxy-benzyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-hydroxybenzyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(3-chlorophenoxy methyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(indol-3-yl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-anisole ethyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-phenyl phenoxymethyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(2-phenyl propyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(3-phenyl propyl)-2-pyrazolin-5-one,

3-(4-leptodactyline)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-methylbenzene ethyl)-2-pyrazolin-5-one,

3-oxyethyl group-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-isopropoxy-2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-styroyl-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-oil of mirbane ethyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-propoxy--2-pyrazolin-5-one,

3-(4-fluoroanilino)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-amino-benzene ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(2-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(7-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(7-skatole-3-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,

3-cyclopentyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-methoxycarbonyl styroyl)-2-pyrazolin-5-one,

3-isopropoxy-4-[(1-isopropyl indole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-leptodactyline)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-sec.-propyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-chlorobenzene amino carbonyl methyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-ethoxycarbonylmethyl group-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(the amino carbonyl methyl of 4-anisole)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

3-(2-aminocarboxyl ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclobutyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(2-dimethylamino carbonyl ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(4-pyridyl)-2-pyrazolin-5-one,

3-cyclopentyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(2,2,3,3-tetramethyl-ring propyl group)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(2-methyl cyclopropyl)-2-pyrazolin-5-one,

3-cyclohexyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-(4-pyridyl)-2-pyrazolin-5-one,

3-(benzothiazole-2-yl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,

3-dimethylamino-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(pyrroles-2-yl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(6-methoxyl group benzo thiazol-2-yl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(7-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(1-skatole-3-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-propyl group-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-antazoline-5-ketone,

The 4-[(indol-3-yl) methylene radical]-3-trifluoromethyl-2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-antazoline-5-ketone,

4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-trifluoromethyl-2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-3-(tertiary butyl)-2-pyrazolin-5-one,

3-ethoxycarbonyl-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(2-methoxycarbonyl ethyl)-2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-(anti--2-phenyl-1-cyclopropyl)-2-pyrazolin-5-one,

3-cyclobutyl-4-{[1-(4-hydroxybutyl) indol-3-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(6-carboxyl-1-skatole-3-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-methoxyl group-1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(1-skatole-3-yl) methylene radical [3-pyrazinyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(1,7-dimethyl indole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(1-skatole-3-yl) methylene radical]-3-(tetrahydrofuran (THF)-3-yl)-2-pyrazolin-5-one,

3-cyclopropyl amino-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(6-carboxyl-1-skatole-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-[(1,7-dimethyl indole-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-isopropoxy-4-[(5-methoxyl group-1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-fluoroanilino)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(1-skatole-3-yl) methylene radical]-3-trifluoroacetamido-2-pyrazolin-5-one,

3-(4-amino-benzene ethyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-amino-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-chlorobenzene ethyl)-4-[(indol-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-oxyethyl group-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(5-isoxazolyl)-4-[(1-skatole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(1-skatole-3-yl) methylene radical]-the 3-tertiary butyl-2-pyrazolin-5-one,

4-[(6-carboxyl-1-skatole-3-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{{1-methyl-6-[2-(4-morpholino) ethyl] the aminocarboxyl indol-3-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(indoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-(4-leptodactyline)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-amino-benzene ethyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-methoxycarbonyl styroyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-(4-formamyl styroyl)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-dimethylamino methyl indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(indoles-2-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

3-isopropoxy-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(1-skatole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(indoles-2-yl) methylene radical]-3-(tetrahydrofuran (THF)-3-yl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-methoxyl group indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(5-nitroindoline-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(indoles-2-yl) methylene radical]-3-sec.-propyl amino-2-pyrazolin-5-one,

3-(4-carboxyl styrene base)-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(indoles-2-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,

3-isopropoxy-4-[(3-skatole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-{[3-(2-methoxycarbonyl-2-kharophen ethyl) indoles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-oxyethyl group-4-[(indoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-oxyethyl group-4-{[3-(4-morpholino methyl) indoles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-(4-morpholino methyl) indoles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(5-methoxyl group indoles-2-yl) methylene radical]-3-(2-pyridyl)-2-pyrazolin-5-one,

4-[(4-chloro-6,7-indoline-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(4-chloro-6,7-indoline-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-oxo-1,5,6,7-indoline-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-dimethylamino methyl indoles-2-yl) methylene radical]-3-oxyethyl group-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-benzyl-2-pyrazolin-5-one,

3-benzyl-4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-the 2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-(4-methoxyl group phenoxymethyl)-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-amino-4-[(7-azaindole-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-(4-methoxy-benzyl)-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-phenylamino-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-(4-xylyl)-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-(4-leptodactyline)-2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-3-(4-leptodactyline)-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-sec.-propyl-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-cyclopropyl-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-cyclobutyl-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-(3-pyridyl)-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-phenyl-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-(4-fluoroanilino)-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-propyl group-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-antazoline-5-ketone,

4-[(7-azaindole-3-yl) methylene radical]-3-trifluoromethyl-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-(tertiary butyl)-2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-3-trifluoromethyl-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-(4-isopropyl benzene amino)-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-(3-methylbenzene amino)-2-pyrazolin-5-one,

4-{[1-(4-hydroxybutyl)-7-azaindole-3-yl] methylene radical }-3-(3-methylbenzene amino)-2-pyrazolin-5-one,

4-[(7-azaindole-3-yl) methylene radical]-3-styroyl-2-pyrazolin-5-one,

3-benzyl-4-[(4-dimethylamino phenyl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(4-dimethylamino phenyl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

The 4-[(4-dimethylamino phenyl) methylene radical]-3-styroyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-dimethylamino phenyl) methylene radical]-the 2-pyrazolin-5-one,

3-isopropoxy-4-[(3-methyl-pyrazol-4-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-methyl-pyrazol-4-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(imidazoles-2-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-cyclopropyl-4-[(imidazoles-2-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(imidazol-4 yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

3-cyclopropyl-4-[(thiophene-2-yl) methylene radical]-the 2-pyrazolin-5-one,

The 4-[(indol-3-yl) methylene radical]-3-sec.-propyl-1-antazoline-5-ketone,

3-isopropoxy-4-[(pyrroles-3-yl) methylene radical]-the 2-pyrazolin-5-one,

4-[(8-hydroxyquinoline-5-yl) methylene radical]-3-isopropoxy-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

3-cyclopropyl-4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-cyclopropyl-2-pyrazolin-5-one,

3-cyclopropyl-4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-cyclopropyl-4-(1-pyrrolidyl methyl)-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5 methylpyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-the 2-pyrazolin-5-one,

3-cyclopropyl-4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

3-pyrazinyl-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

3-pyrazinyl-4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-2-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(2 furyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

3-(2-furyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

3-(2-furyl)-4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-the 2-pyrazolin-5-one,

3-(2-furyl)-4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2 furyl)-2-pyrazolin-5-one,

4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-furyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(2 furyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(2-furyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-thienyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(2-thienyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

3-(4-pyrimidyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(4-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

3-(5-pyrimidyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{{4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(5-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

3-(2-pyrimidyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical)-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(2-pyrimidyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

3-(3-pyridazinyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(3-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

3-(4-pyridazinyl)-4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-the 2-pyrazolin-5-one,

4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(4-pyridazinyl)-2-pyrazolin-5-one,

4-[(3,5-dimethyl-4-(1-pyrrolidyl methylpyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3,5-dimethyl pyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-ethylamino ethyl)-pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[3,5-dimethyl-4-(2-phenylamino ethyl) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{{3,5-dimethyl-4-[2-(4-pyridyl methylamino-) ethyl] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[4-(2-propyloic)-3,5-dimethyl pyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-[(4-diethylin methyl-3-sec.-propyl-5-methylpyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[4-(1-pyrrolidyl methyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{{3-sec.-propyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{{4-[3-(1-pyrrolidyl) propyl group]-3-sec.-propyl-5-methylpyrrole-2-methylene }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[3-sec.-propyl-5-methyl-4-(4-piperidino-(1-position only) butyl) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{{4-[3-(4-pyridyl methylamino-) propyl group]-3-sec.-propyl-5-methylpyrrole-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[4-(4-dimethylamino butyl)-3-sec.-propyl-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-[(3-cyclopropyl-4-diethylin methyl-5-methylpyrrole-2-yl) methylene radical]-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[2-(1-pyrrolidyl) ethyl] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[2-two (methoxy ethyl) amino-ethyl]-5-methylpyrrole-2-yl } methylene radical)-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-4-(3-diethylin propyl group)-5-methylpyrrole-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-4-[3-(2,5-dimethyl-1-pyrrolidyl) propyl group]-5-methylpyrrole-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(3-phenyl methylamino-propyl group) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{{3-cyclopropyl-5-methyl-4-[4-(1-pyrrolidyl) butyl] pyrroles-2-yl } methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[3-cyclopropyl-5-methyl-4-(the amino butyl of 4-cyclobutyl) pyrroles-2-yl] methylene radical }-3-(1,2,4-triazine-3-yl)-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-4-[2-(1-pyrrolidyl ethyl)]-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-4-[2-(4-pyridyl methylamino-ethyl)]-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino-ethyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-4-[2-(1-pyrrolidyl ethyl)]-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical)-3-pyrazinyl-2-pyrazolin-5-one,

4-{5-methyl-4-[2-(4-pyridyl methylamino-ethyl)]-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino-ethyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-3-ethyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-ethyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-ethyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-ethyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-N-ethyl pyrrole N--2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino-ethyl)-5-methyl-3-N-ethyl pyrrole N--2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclobutyl-4-(2-diethyllaminoethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclobutyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclobutyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclobutyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-cyclobutyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino-ethyl)-5-methyl-3-cyclobutyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopentyl-4-(2-diethyllaminoethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclopentyl-5-methyl-4-[2-(1-pyrrolidyl ethyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopentyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclopentyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-cyclopentyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino-ethyl)-5-methyl-3-cyclopentyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclohexyl-4-(2-diethyllaminoethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclohexyl-5-methyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclohexyl-4-(2-ethylamino ethyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclohexyl-5-methyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-cyclohexyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino-ethyl)-5-methyl-3-cyclohexyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-phenyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-phenyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-phenylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino-ethyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino-ethyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-pyridyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-pyridyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-pyridyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino-ethyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-pyrazinyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-pyrazinyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-pyrazinyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-imidazolyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-imidazolyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-imidazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[5-methyl-3-(2-pyrimidyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-pyrimidyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-furyl)-4-[2-(1-pyrrolidyl ethyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-furyl)-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{4-[2-(1-imidazolyl) ethyl]-5-methyl-3-(2-furyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methylol-3-sec.-propyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methylol-3-sec.-propyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-5-methylol-3-sec.-propyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[4-(2-diethyllaminoethyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-two cyclopropyl-4-[2-(1-pyrrolidyl ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino ethyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-two cyclopropyl-4-[2-(4-pyridyl methylamino-ethyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) ethyl]-3,5-two cyclopropyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino-ethyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-4-[2-(1-pyrrolidyl methyl)]-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-4-[2-(4-pyridyl methylamino-methyl)]-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-trifluoromethyl pyrpole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino methyl)-5-methyl-3-trifluoromethyl pyrpole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-4-[2-(1-pyrrolidyl methyl)]-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-4-[2-(4-pyridyl methylamino-methyl)]-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{4-[2-(1-imidazolyl) methyl]-5-methyl-3-tertiary butyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino methyl)-5-methyl-3-tertiary butyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-3-ethyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-3-ethyl-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-ethyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-ethyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-ethyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-N-ethyl pyrrole N--2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino methyl)-5-methyl-3-N-ethyl pyrrole N--2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclobutyl-4-(2-diethylin methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclobutyl-4-(2-dimethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclobutyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclobutyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclobutyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-cyclobutyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino methyl)-5-methyl-3-cyclobutyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopentyl-4-(2-diethylin methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopentyl-4-(2-dimethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclopentyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopentyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclopentyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-[2-(1-imidazolyl) methyl]-5-methyl-3-cyclopentyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino methyl)-5-methyl-3-cyclopentyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclohexyl-4-(2-diethylin methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclohexyl-4-(2-dimethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclohexyl-5-methyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclohexyl-4-(2-ethylamino methyl)-5-methylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3-cyclohexyl-5-methyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-cyclohexyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino methyl)-5-methyl-3-cyclohexyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-phenyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-phenyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-phenylpyrrole-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino methyl)-5-methyl-3-phenylpyrrole-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methyl }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(4-methoxyphenyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino methyl)-5-methyl-3-(4-methoxyphenyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-pyridyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-pyridyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(2-pyridyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-amino methyl)-5-methyl-3-(2-pyridyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-pyrazinyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-pyrazinyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-pyrazinyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-pyrazinyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-imidazolyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-imidazolyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(2-imidazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(2-imidazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{5-methyl-3-(2-pyrimidyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-pyrimidyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(the 1-imidazolyl } methyl]-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(2-pyrimidyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethyllaminoethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylaminoethyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(3-isoxazolyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(3-isoxazolyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-(2-diethylin methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-furyl)-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methyl-3-(2-furyl)-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methyl-3-(2-furyl) pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino methyl)-5-methyl-3-(2-furyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methylol-3-sec.-propyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{5-methylol-3-sec.-propyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-5-methylol-3-sec.-propyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-cyclopropyl amino methyl)-5-methylol-3-sec.-propyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-diethylin methyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-dimethylamino methyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{3,5-two cyclopropyl-4-[2-(1-pyrrolidyl methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[4-(2-ethylamino methyl)-3,5-two cyclopropyl pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3,5-two cyclopropyl-4-[2-(4-pyridyl methylamino-methyl)] pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{{4-[2-(1-imidazolyl) methyl]-3,5-two cyclopropyl pyrroles-2-yl } methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-[(4-cyclopropyl amino methyl-3,5-two cyclopropyl pyrroles-2-yl) methylene radical]-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopropyl amino methyl-5-methyl-4-(2-diethyllaminoethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-cyclopropyl amino methyl-5-methyl-4-(2-hydroxyethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one,

4-{[3-dimethylamino methyl-5-methyl-4-(2-diethyllaminoethyl) pyrroles-2-yl] methylene radical-3-pyrazinyl-2-pyrazolin-5-one and

4-{[3-methylol-5-methyl-4-(2-diethyllaminoethyl) pyrroles-2-yl] methylene radical }-3-pyrazinyl-2-pyrazolin-5-one.

22. the compound of claim 17, compound wherein are the mixture of steric isomer.

23. the compound of claim 22, steric isomer wherein is an enantiomorph.

24. the method for claim 23, steric isomer wherein are E and Z isomer.

25. the method for claim 17, compound wherein are the mixtures of constitutional isomer.

26. the method for claim 25, constitutional isomer wherein is a tautomer.

27. the compound of claim 17, wherein R one or morely is selected from following one group substituting group and replaces by independent of each other: halogen, C ₁-C ₆Alkyl, R ³O-, hydroxyl, HOC (O)-, R ³OC (O)-, R ³OC (O) R ⁶, R ³OR ⁶-, nitro ,-NR ⁴R ⁵, R ³CO-,-(CH ₂) _n-R ⁷,-C (O) (CH ₂) _n-R ⁷,-C (O)-(CH ₂) _n-C (O)-R ⁷,-C (O) NR ⁴(CH ₂) _nR ⁷,-C (O) O (CH ₂) _nR ⁷,-R ⁶NR ⁴R ⁵,-R ⁶N (R ⁴)-R ⁶R ⁷,-R ⁶OC (O) (CH ₂) _nR ⁷, unsubstituted or the phenyl, morpholinyl, benzothiazolyl or the pyrazinyl that replace;

Wherein the phenyl of Qu Daiing, morpholinyl, benzothiazolyl or pyrazinyl are selected from following one group substituting group and replace by one or more: halogen, hydroxyl ,-NR ⁴R ⁵, nitro, C ₁-C ₆Alkyl or R ³O;

R ⁶Be C ₁-C ₆Alkyl or morpholinyl;

R ⁷Be alkoxyl group, C ₁-C ₆Alkylpiperazine, hydroxyl, R ³O-, R ³C (O)-or-NR ⁴R ⁵

28. the compound of claim 27, wherein R is pyrryl, indyl, azaindolyl, phenyl, pyrazolyl, imidazolyl, thienyl, 4,5,6,7-tetrahydro indole base or quinolyl.

29. the compound of claim 28, wherein R is pyrroles-2-base, pyrroles-3-base, indoles-2-base, indol-3-yl, azaindole-3-base, pyrazoles-4-base, imidazoles-2-base, imidazol-4 yl, thiophene-2-base or quinoline-5-base.

30. the compound of claim 17 or 29, wherein R ¹Be trifluoromethyl, amino, cyclopropylamino, methyl, ethyl, propyl group, sec.-propyl, cyclopropyl, 2-methyl cyclopropyl, 2,2,3,3-tetramethyl-ring propyl group, 2-phenycyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl ,-(CH ₂) _p-O-phenyl ,-(CH ₂) _p-O-(4-methoxyphenyl) ,-(CH ₂) _p-O-(4-chloro-phenyl-) ,-(CH ₂) _p-O-(4-aminomethyl phenyl) ,-(CH ₂) _p-O-(3-aminomethyl phenyl) ,-(CH ₂) _p-O-(4-phenyl) ,-(CH ₂) _p-O-(4-hydroxyphenyl) ,-(CH ₂) _p-O-(4-nitrophenyl) ,-(CH ₂) _p-O-(4-aminophenyl) ,-(CH ₂) _p-O-(4-formamyl phenyl) ,-(CH ₂) _p-O-(4-methoxycarbonyl phenyl) ,-the NH-phenyl ,-NH-(4-methoxyphenyl) ,-NH-(4-chloro-phenyl-) ,-NH-(4-fluorophenyl) ,-NH-(4-isopropyl phenyl), isopropoxy, oxyethyl group, cyclopentyloxy ,-(CH ₂) _p-indyl ,-(CH ₂) _p-pyridyl ,-(CH ₂) _p-benzothiazolyl ,-(CH ₂) _p-pyrryl ,-(CH ₂) _p-tetrahydrofuran base ,-(CH ₂) _p-pyrazinyl ,-(CH ₂) _p-furyl ,-(CH ₂) _p-thienyl ,-(CH ₂) _p-phenyl ,-(CH ₂) _p-isoxazolyls ,-(CH ₂) _p-(5-methyl-isoxazole base) ,-(CH ₂) _p-pyrimidyl ,-(CH ₂) _p-pyridazinyl ,-(CH ₂) _n-C (O)-OMe ,-(CH ₂) _n-C (O)-OEt and unsubstituted or by one or more Cl, F, OMe, methyl or the amino benzyl that replaces,

Wherein p is the integer of 1-3.

31. the compound of claim 30, wherein R is unsubstituted or is selected from following group and replaces by one or more: Br, Cl, F, amino methyl, N, N-dimethylamino methyl, carboxyl, carboxymethyl, propyloic, carbonyl methyl, carbonyl ethyl, methoxycarbonyl, ethoxycarbonyl, phenyl, 4-morpholino methyl ,-C (O)-O-(CH ₂) ₂-N (Me) ₂,-C (O)-O-(CH ₂) ₂-N (Et) ₂,-C (O)-O-CH ₂-N (Me) ₂,-C (O)-O-(CH ₂) ₂-N (Me) ₂,-CH ₂-NH-C (O)-CF ₃Be selected from unsubstituted or by one or more Br, Cl, F, hydroxyl, nitro, amino or C ₁-C ₆The following groups that alkyl replaces: methyl, ethyl, propyl group, sec.-propyl, butyl and phenyl.

32. the compound of claim 17 is used for influencing the application of the medicine of curer hyperproliferation disease in preparation.

33. pharmaceutical composition wherein contains compound and the pharmaceutically acceptable carrier or the thinner of claim 17.

34. the pharmaceutical composition of claim 33 wherein contains compound and the pharmaceutically acceptable carrier or the thinner of claim 21.