EP1678153A1

EP1678153A1 - Thiozolidinones, production and use thereof as medicaments

Info

Publication number: EP1678153A1
Application number: EP04791006A
Authority: EP
Inventors: Volker Schulze; Knut Eis; Lars Wortmann; Wolfgang Schwede; Gerhard Siemeister; Hans Briem; Herbert Schneider; Uwe EBERSPÄCHER; Holger Hess-Stumpp
Original assignee: Schering AG
Current assignee: Bayer Pharma AG
Priority date: 2003-10-31
Filing date: 2004-10-26
Publication date: 2006-07-12
Also published as: ECSP066588A; KR20060098374A; PE20050924A1; ZA200604432B; TW200530230A; BRPI0416005A; RS20060294A; AR046347A1; US20070037862A1; AU2004285682A1; EA200600833A1; NO20062453L; CN1902185A; JP2007509892A; DE10351744A1; WO2005042505A1; IL175245A0; CR8385A; CA2544267A1

Abstract

The invention relates to thiazolidinones of general formula ( I ), wherein Q, A, B, X, R<1> and R<2> have the meaning cited in the description, and the general formula (IA) wherein Q, A, B, X, R<1> and R<2a> have the meaning cited in the description, to the production and use thereof as inhibitors of the Polo Like Kinase (PLK) for the treatment of different diseases. The invention also relates to intermediate products for the production of thiazolidinones.

Description

Thiazolidinones, their preparation and use as pharmaceuticals

The invention relates to thiazolidones, their preparation and use as inhibitors of the Polo Like Kinase (Pik) for the treatment of various diseases.

Tumor cells are characterized by an unrestrained cell cycle process. This is based on the one hand on the loss of control proteins such as RB, p16, p21, p53, etc., and the activation of so-called accelerators of the cell-cycle process, the cyclin-dependent kinases (Cdk's). The Cdk's are a pharmacy recognized anti-tumor target protein. In addition to the Cdk's new Zeil cycle regulating serine / threonine kinases, so-called 'polo-like kinases' have been described, which not only in the regulation of the cell cycle but also in the coordination with other processes during mitosis and cytokinesis (formation of the Spindle apparatus, chromosome separation) are involved. Therefore, this class of proteins provides an interesting target for the therapeutic intervention of proliferative diseases such as cancer (Descombes and Nigg. Embo J, 17, 1328ff, 1998, Glover et al., Genes Dev 12, 3777ff, 1998).

A high expression rate of Plk-1 has been reported in non-small cell lung cancer (Wolf et al Oncogene, 14, 543ff, 1997), in melanomas (Strebhardt et al., JAMA, 283, 479ff, 2000). squamous cell carcinomas' (Knecht et al., Cancer Res, 59, 2794ff, 1999) and in 'esophageal carcinomas' (Tokumitsu et al., Int J Oncol 15, 687ff, 1999).

A correlation of high expression rate in tumor patients with poor prognosis was shown for various tumors (Strebhardt et al JAMA, 283, 479ff, 2000, Knecht et al., Cancer Res, 59, 2794ff, 1999 and Tokumitsu et al., Int J Oncol 15 , 687ff, 1999).

Constitutive expression of Plk-1 in NIH-3T3 cells resulted in malignant transformation (increased proliferation, growth in soft agar, colony formation and tumor development in nude mice (Smith et al., Biochem Biophys Res Comm, 234, 397ff. , 1997). Microinjection of Plk-1 antibodies into HeLa cells resulted in defective mitosis (Lane et al., Journal Cell Biol, 135, 1701 et seq., 1996).

A '20 -mer 'antisense oligo inhibited the expression of Plk-1 in A549 cells and stopped their viability. Likewise, a clear anti-tumor effect could be shown in nude mice (Mundt et al., Biochem Biophys ResComm, 269, 377ff., 2000).

Microinjection of anti-PIk antibodies into nonimmortalized human Hs68 cells, when compared to HeLa cells, revealed a significantly higher fraction of cells that remained in growth arrest at G2 and showed far fewer signs of defective mitosis (Lane et al. Journal Cell Biol, 135, 1701ff, 1996).

Unlike tumor cells, antisense oligo molecules did not inhibit the growth and viability of primary human mesangial cells (Mundt et al., Biochem Biophys ResComm, 269, 377ff., 2000).

In mammals, in addition to Plk-1, three other polo-kinases have been described that are induced as a mitogenic response and exert their function in the G1 phase of the cell cycle. These are on the one hand the so-called Prk / Plk-3 (the human homolog of the mouse Fnk = fibroblast growth factor induced kinase, Wiest et al, Genes, Chromosomes & Cancer, 32: 384ff, 2001), Snk / Plk-2 (serum induced kinase, Liby et al., DNA Sequence, 11, 527-33, 2001) and sak / Plk4 (Fode et al., Proc. Natl. Acad. Sci. U. SA, 91, 6388ff, 1994).

Inhibition of Plk-1 and other polo family kinases, such as Plk-2, Plk-3 and Plk-4 thus represents a promising approach to the treatment of various diseases.

The sequence identity within the polypic spiking domains is between 40 and 60%, so that in part interaction of inhibitors of a kinase with one or more other kinases of this family occur. Depending on the structure of the However, the effect of the inhibitors can also be selective or preferred on only one polo family kinase.

International application WO03 / 093249 discloses thiazolidinone compounds which inhibit polo family kinases.

The object of the present invention is to provide further substances which inhibit kinases of the polo family in the nanomolar range.

It has now been found that compounds of general formula I

(I),

in the

Q is aryl or heteroaryl,

A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted by identical or different substituents with halogen, hydroxy, C ₃ -C ₆ -heterocycloalkyl or with the group -NR ³ R ⁴ or - CO (NR ³ ) -M substituted dC ₃ alkyl or CC ₆ - alkoxy, where the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by one or more - ( CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself may be mono- or polysubstituted, identically or differently, with C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₁ -C ₆ -hydroxyalkyl or with the group -NR ³ R ⁴ , or for -NR ³ (CO) -L, -NR ³ (CO) -NR ³ -L, -COR ⁶ , -CO (NR ³ ) -M, - NR ³ (CS) NR ³ R ⁴ , -NR ³ SO ₂ -M, -SO ₂ -NR ³ R ⁴ or -SO ₂ (NR ³ ) -M, L is optionally mono- or polysubstituted by identical or different substituents with C ₁ -C ₆ -hydroxyalkoxy, C ₁ -C ₆ -alkoxyalkoxy, C ₃ -Cβ-heterocycloalkyl or with the group -NR ³ R ⁴ , substituted Ci- Cβ-alkyl or heteroaryl, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds can be contained in the ring and / or the ring itself optionally substituted one or more times, identically or differently, with C -C ₆ alkyl, C ₃ - C ₆ -cycloalkyl may be, Cι-C ₆ hydroxyalkyl or substituted with the group -NR ³ R ^4, is,

M represents optionally mono- or polysubstituted, identically or differently, with the group -NR ³ R ⁴ or C ₃ -C ₆ -heterocycloalkyl-substituted CC ₆ -alkyl, X stands for -NH- or -NR ⁵ -, R ¹ for optionally mono- or polysubstituted by identical or different halogens substituted C- | -C ₄ alkyl, C ₃ -CycloalkyI, allyl or propargyl, R ^{2 is} hydrogen or optionally mono- or polysubstituted, identical or different with halogen, hydroxy , cyano, C ₆ - alkyl, Cι-C ₆ -alkoxy, -C ₆ hydroxyalkyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ - heterocycloalkyl, Cι-C ₆ alkynyl, aryl, aryloxy, heteroaryl or Ci-Cβ-alkyl substituted with the group -S-C ₁ -C ₆ -alkyl, -COR ⁶ , -NR ³ R ⁴ , -NR ³ (CO) -L or -NR ³ COOR ⁷ , -C-C ₆ - Alkoxy, C ₁ -C ₆ - Alkenyl, C ₁ -C ₆ -alkynyl, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -heterocycloalkyl, aryl or heteroaryl, where the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms may optionally and / or may be interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and wherein aryl, heteroaryl, C ₃ -C ₆ - Cycloalkyl and / or the C ₃ -Cβ heterocycloalkyl ring each itself optionally optionally mono- or polysubstituted, identical or different, with cyano, halogen, hydroxy, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -hydroxyalkyl, optionally one or more times, C ₁ -C ₆ -cycloalkyl, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -heterocycloalkyl, aryl, benzyl or heteroaryl which may be substituted identically or differently by halogen, or for the group -NR ³ R ⁴ , -NR ³ (CO) -L, -NR ³ (CS) NR ³ R ⁴ , or R ² and R ⁵ together form a C ₃ - C ₆ -Heterocycloalkylring form which is interrupted at least once by nitrogen and may optionally be interrupted by one or more times by oxygen or sulfur and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally mono- or polysubstituted by identical or different cyano, halogen, hydroxy, C ₁ -C ₄ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₁ -C ₄ -alkyl ₆ -hydroxyalkyl, C -C ₆ -alkoxyalkyl or with the group -NR ³ R ⁴ or -COR ⁶ may be substituted and / or optionally with one or more times, same or different with halogen, Ci-Cβ-alkoxy or with the Group - COR ⁶ substituted aryl or heteroaryl may be substituted,

R ³ and R ⁴ independently of one another are hydrogen or optionally mono- or polysubstituted by identical or different radicals Halogen, hydroxy, C ₃ -C ₆ heterocycloalkyl, _Cι-C6 hydroxyalkoxy or with the group -NR ³ R ⁴ is substituted Cι-C ₆ -alkyl, C ₆ - alkoxy, -CO-Cι-C ₆ - Alkyl or aryl, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds in the ring can be contained and wherein the C ₃ -C itself in each case optionally mono- or polysubstituted ₆ -heterocycloalkyl, identically or differently, with cyano, halogen, Cι-C ₆ -alkyl, C ₆ -Hydroxyalkyl, -CC ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, or may be substituted by the group -NR ³ R ⁴ or -CO-NR ³ R ⁴ , or R ³ and R ⁴ together form a C ₃ - Form C ₆ -Heterocycloalkylring which is interrupted at least once by nitrogen and optionally mono- or polysubstituted by oxygen or Sulfur may be interrupted and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and / or the heterocycloalkyl itself or polysubstituted, identically or differently, with -CC ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₁ -C ₆ -hydroxyalkyl, -CC ₆ -alkoxyalkyl, cyano, hydroxy or with the group -NR ³ R ⁴ .

R ⁵ is optionally substituted one or more times, identically or differently with halogen, hydroxy, cyano, CrC ₆ alkoxy, C ₃ -C ₆ cycloalkyl, C ₃ - Cβ-heterocycloalkyl, or substituted with the group -NR ³ R ⁴ Cι -C ₆ alkyl, C -C ₆ alkenyl, -CC ₆ -Alkinyi, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds can be contained in the ring and wherein the C ₃ -C itself in each case optionally mono- or polysubstituted ₆ -heterocycloalkyl, identically or differently with cyano, halogen, _Cι-C6 alkyl, -C ₆ hydroxyalkyl, CrC ₆ -Alkoxy, C ₃ -C ₆ -cycloalkyl, or may be substituted by the group -NR ³ R ⁴ or -CO-NR ³ R ⁴ , R ^{6 is} hydroxy, C ₁ -C ₆ -alkyl, CC ₆ -alkoxy or the Group -NR ³ R ⁴ , R ^{7 is} - (CH ₂ ) _n -aryl or - (CH ₂ ) _n -heteroaryl and n is 1-6, and their solvates, hydrates, stereoisomers, diastereomers, enantiomers and Salts, with the proviso that the following compounds do not fall under the general formula (I):

{2-Cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) - ylidenes] -acetylamino } -acetic acid methyl ester,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- pyridin-3-ylmethyl-acetamides, 2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or

Z)) - ylidene] -N- (3-imidazol-1-yl-propyl) -acetamide,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- (4-fluorobenzyl) acetamides, 2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] thiazolidine (2- (E or Z)) - ylidenes] - N - (3-morpholin-4-yl-propyl) -acetamides,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- (2-morpholin-4-yl-ethyl) -acetamide,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- [3- (2-oxopyrrolidin-1-yl) -propyl] -acetamide, 2-cyano-N-cyclohexyl-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth- (E / Z) -ylidene] - thiazolidine (2- (E or Z)) - ylidenes] -acetamides,

4- {2-Cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) - ylidenes] acetylamino} -piperidine-1-carboxylic acid ethyl ester, 2-Cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or

Z)) - ylidene] -N- (3-hydroxy-propyl) -acetamide,

2-Cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or

Z)) - ylidenes] - N - (4-methoxybenzyl) acetamides, 2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene ] -thiazolidine (2- (E or

Z)) - ylidene] -N- [2- (4-hydroxy-phenyl) -ethyl] -acetamide,

N-Allyl-2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth- (E / Z) -ylidene] -thiazoIidin- (2-

(E or Z)) - ylidenes] -acetamides,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- (2-hydroxy-ethyl) -acetamide,

Z)) - ylidene] -N- (4-hydroxy-butyl) -acetamide,

Z)) - ylidenes] - N - (6-hydroxy-hexyl) -acetamides, 2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene ] -thiazolidine (2- (E or

Z)) - ylidene] -acetamide,

2-cyano-N-ethyl-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth- (E / Z) -ylidene] -thiazolidine

(2- (E or Z)) - ylidenes] -acetamides,

2-Cyano-2- [3-ethyl-5- [1- (4-methoxy-phenylamino) -methyl- (E / Z) -ylidene] -4-oxo-thiazolidine (2- (E or Z)) -ylidene] -N, N-dimethyl-acetamide,

Z)) - ylidene] -N, N-dimethyl-acetamdie,

6 - {[2- [1-Cyano-1-dimethylcarbamoyl-meth (E or Z) -ylidene] -3-ethyl-4-oxothiazolidine (5- (E / Z)) -ylidenemethyl] -amino } -naphthalenes-2-carboxylic acid, 4 - {[2- [1-cyano-1-dimethylcarbamoyl-meth (E or Z) -ylidene] -3-ethyl-4-oxothiazolidine (5- (E / Z)) - ylidenemethyl] -amino} -benzoic acid,

2-cyano-2- [3-ethyl-5- [1- (4-hydroxy-phenylamino) -meth (E / Z) -ylidene] -4-oxo-thiazolidine (2- (E or Z)) -ylidene] -N, N-dimethyl-acetamide,

4 - {[2- [1-Cyano-1-dimethylcarbamoyl-meth (E or Z) -ylidene] -3-ethyl-4-oxothiazolidine (5- (E / Z)) -ylidenemethyl] -amino } benzamide,

2-cyano-2- [3-ethyl-5- [1- (4-hydroxymethyl-phenylamino) -meth (E / Z) -ylidene] -4-oxo-thiazolidine (2- (E or Z)) -ylidene] -N, N-dimethyl-acetamides, are suitable inhibitors of polo family kinases. The compounds of the general formula I according to the invention essentially inhibit the polo like kinases, as well as their action for example against cancer, such as solid tumors and leukemia, autoimmune diseases such as psoriasis, alopecia, and multiple sclerosis, chemotherapeutic-induced alopecia and mucositis, cardiovascular diseases, such as stenoses, atherosclerosis and restenosis, infectious diseases such. As by unicellular parasites such as Trypanosoma, Toxoplasma or Plasmodium, or caused by fungi, nephrological diseases such. Glomerulonephritis, chronic neurodegenerative diseases such as Huntington's disease, amyotropic lateral sclerosis, Parkinson's disease, AIDS dementia and Alzheimer's disease, acute neurodegenerative diseases such as brain ischaemia and neurotrauma, viral infections such as. As cytomegalovirus infections, herpes, hepatitis B and C, and HIV-based diseases.

Stereoisomers are to be understood as meaning E / Z and R / S isomers and mixtures of E / Z and R / S isomers.

Alkyl is in each case a straight-chain or branched alkyl radical, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl and decyl.

Alkoxy is in each case a straight-chain or branched alkoxy radical, such as, for example, methyloxy, ethyloxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy, sec. Butyloxy, pentyloxy, isopentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy or decyloxy.

The alkenyl substituents are in each case straight-chain or branched, for example the following radicals being meant: vinyl, propen-1-yl, propen-2-yl, but-1-en-1-yl, but-1-en-2-yl , But-2-en-1-yl, but-2-en-2-yl, 2-methyl-prop-2-en-1-yl, 2-methyl-prop-1-en-1-yl, But -1-en-3-yl, but-3-en-1-yl, allyl.

Alkynyl is in each case to be understood as meaning a straight-chain or branched alkynyl radical which contains 2-6, preferably 2-4, C atoms. For example, the following radicals called: acetylene, propyn-1-yl, propyn-3-yl, but-1-yn-1-yl, but-1-yn-4-yl, but-2-yn-1-yl, but-1 in-3-yl, etc.

Heterocycloalkyl stands for an alkyl ring comprising 3 to 6 carbon atoms which, instead of the carbon, has one or more identical or different heteroatoms, such as, for example, B. oxygen, sulfur or nitrogen and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and at one or more Carbon, nitrogen or sulfur optionally independently of one another may contain a further substituent. Substituents on the heterocycloalkyl ring may be:

Cyano, halogen, hydroxy, Cι-C ₆ -alkyl, C ₆ alkoxy, CRCE alkoxyalkyl, Cι-C ₆ - hydroxyalkyl, C ₃ -C ₆ cycloalkyl, aryl or the group -NR ³ R ^4, - CO-NR ³ R ⁴ , -SO ₂ R ³ or -SO ₂ NR ³ R ⁴ .

As heterocycloalkyl z. Examples are: oxiranyl, oxethanyl, aziridinyl, azetidinyl, tetrahydrofuranyl, pyrrolidinyl, dioxolanyl, imidazolidinyl, pyrazolidinyl, dioxanyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, trithianyl, quinuclidinyl, pyrolidonyl, N-methylpyrrolidinyl, 2-hydroxymethylpyrrolidinyl, Hydroxypyrrolidinyl, N-methylpiperazinyl, N-acetylpiperazinyl, N-

Methylsulfonylpiperazinyl, 4-hydroxypiperidinyl, 4-aminocarbonylpiperidinyl, 2-hydroxyethylpiperidinyl, 4-hydroxymethylpiperidinyl, nortropinyl, 1, 1-dioxothiomorpholinyl, etc.

Cycloalkyl is to be understood as meaning monocyclic alkyl rings such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl, but also bicyclic rings or tricyclic rings such as, for example, adamantanyl. The cycloalkyl may optionally also be benzo-fused, e.g. (Tetralin) yl etc.

Halogen is in each case fluorine, chlorine, bromine or iodine.

The aryl radical has in each case 6 to 12 carbon atoms, for example naphthyl, biphenyl and in particular phenyl. The heteroaryl group comprises in each case 3 to 16 ring atoms and may contain one or more identical or different heteroatoms, such as oxygen, nitrogen or sulfur in the ring, instead of the carbon, and may be mono-, bi- or tricyclic, and may additionally be benzo-fused in each case.

For example:

Thienyl, furanyl, pyridyloxy, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,

Isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, etc. and benzo derivatives thereof, such as. Benzofuranyl, benzothienyl, benzoxazolyl, benzimidazolyl, indazolyl, indolyl, isoindolyl, etc .; or pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc. and benzo derivatives thereof, such as. Quinolyl, isoquinolyl, etc .; or oxepinyl, azocinyl, indolizinyl, indolyl, indolinyl, isoindolyl, indazolyl, benzimidazolyl, purinyl, etc. and benzo derivatives thereof; or quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl, tetralinyl etc.

Preferred heteroaryl radicals are, for example, 5-ring heteroaromatics, such as thiophene, furanyl, oxazolyl, thiazole, imidazolyl and benzo derivatives thereof and 6-membered heteroaromatics, such as pyridinyl, pyrimidinyl, triazinyl, quinolinyl, isoquinolinyl and benzo derivatives thereof.

The aryl radical comprises in each case 3 to 12 carbon atoms and may each be benzo-fused. Examples which may be mentioned are: cyclopropenyl, cyclopentadienyl, phenyl, tropyl, cyclooctadienyl, indenyl, naphthyl, azulenyl, biphenyl, fluorenyl, anthracenyl, tetralinyl, etc.

Isomers are to be understood as meaning chemical compounds of the same empirical formula but of different chemical structure. In general, one distinguishes constitutional isomers and stereoisomers. Constitutional isomers have the same molecular formula, but differ in how their atoms or atomic groups are linked. These include functional isomers, positional isomers, tautomers or valence isomers.

Stereoisomers basically have the same structure (constitution) - and therefore also the same molecular formula - but differ by the spatial arrangement of the atoms.

In general, a distinction is made between configuration isomers and conformational isomers. Configuration isomers are stereoisomers that can only be converted into each other by bond breaking. These include enantiomers, diastereomers and E / Z (ice / trans) isomers.

Enantiomers are stereoisomers that behave in the same way as image and mirror image and have no plane of symmetry. All stereoisomers that are not enantiomers are called diastereomers. A special case is E / Z (ice / trans) isomers of double bonds.

Conformational isomers are stereoisomers that can be converted into each other by the rotation of single bonds.

For the differentiation of the isomeric species from each other, see also the IUPAC rules section E (Pure Appl. Chem. 45, 11-30, 1 976).

The compounds of general formula I according to the invention also include the possible tautomeric forms and include the E or Z isomers or, if a chiral center is present, also the racemates and enantiomers. These include double bond isomers.

The compounds according to the invention can also be present in the form of solvates, in particular of hydrates, the compounds according to the invention accordingly containing polar solvents, in particular of water, as structural element of the crystal lattice of the compounds according to the invention. The proportion of polar solvent, in particular water, can be present in a stoichiometric or even unstoichiometric ratio. In the case of stoichiometric solvates, hydrates, we also speak of hemi, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta-, etc. solvates or hydrates. If an acidic function is present, suitable salts are the physiologically tolerated salts of organic and inorganic bases, such as, for example, the readily soluble alkali and alkaline earth salts and N-methyl-glucamine, dimethyl-glucamine, ethyl-glucamine, lysine, 1,6-hexadiamine , Ethanolamine, glucosamine, sarcosine, serinol, tris-hydroxy-methyl-amino-methane, A inopropandiol, Sovak base, 1-amino-2,3,4-butanetriol.

If a basic function is included, the physiologically acceptable salts of organic and inorganic acids are suitable, such as hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, tartaric acid and the like.

Particular preference is given to those compounds of the general formula I in which Q is phenyl, naphthyl, quinolinyl, benzimidazolyl, indolyl, indazolyl, thiazolyl, imidazolyl or pyridyl, A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted, identically or differently, with halogen, hydroxyl, C ₃ -C ₆ -heterocycloalkyl or with the group -NR ³ R ⁴ or -CO (NR ³ ) -M-substituted dC ₃ -alkyl or C ₁ -C ₆ -alkyl Alkoxy, where the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or may be interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally one or more times, identically or differently with Ci-Cβ-alkyl, C ₃ -C ₆ -cycloalkyl, CrC ₆ - hydroxyalkyl or with the group -NR ³ R ⁴ may be substituted, or -NR ³ (CO) -L, -NR ³ (CO) -NR ³ -L, -COR ^6, -CO (NR ³⁾ -M, - NR ³ (CS) NR ³ R ⁴ , -NR ³ SO ₂ -M, -SO ₂ -NR ³ R ⁴ or -SO ₂ (NR ³ ) -M, L is optionally mono- or polysubstituted, identically or differently Cι-C ₅ hydroxyalkoxy, _C-C6 alkoxyalkoxy, C ₃ -C ₆ - heterocycloalkyl or with the group -NR ³ R ^4, substituted d- C ₆ alkyl, or heteroaryl, wherein the heterocycloalkyl itself optionally substituted by one or more Nitrogen, oxygen and / or sulfur atoms may be interrupted and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally substituted one or more times, identically or differently, with Cι-C ₆ alkyl, C ₃ -, is C ₆ cycloalkyl, Ci-C _δ hydroxyalkyl, or may be substituted with the group -NR ³ R ⁴ .

M is C ₁ -C ₆ -alkyl which is optionally mono- or polysubstituted identically or differently with the group -NR ³ R ⁴ or C ₃ -C ₆ -heterocycloalkyl, X is -NH- or -NR ⁵ -, R ^{1 is} optionally is mono- or polysubstituted by identical or different halogen-substituted dC ₄ alkyl, C ₃ -cycloalkyl, allyl or propargyl, R ² is hydrogen or one is optionally substituted one or more times, identically or differently with halogen, hydroxy, cyano, CC ₆ - alkyl, _Cι-C6 alkoxy, CRCE hydroxyalkyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ - heterocycloalkyl, Cι-C ₆ alkynyl, aryl, aryloxy, heteroaryl or with the group -S-C _{r is} C ₆ -alkyl, -COR ⁶ , -NR ³ R ⁴ , -NR ³ (CO) -L or -NR ³ COOR ⁷ substituted C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, CC ₆ -alkenyl, C ₁ -C ₆ -alkynyl, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -heterocycloalkyl, aryl or heteroaryl, where the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring optionally and / or one or more double bonds can be contained in the ring and wherein aryl, heteroaryl, C ₃ -C ₆ -cycloalkyl and / or the C ₃ -C ₆ - heterocycloalkyl ring each themselves optionally optionally one or more times, same or different with cyano, halogen, hydroxy, Ci-Cβ--alkyl, Cι-C ₆ hydroxyalkyl, optionally substituted one or more times, identically or differently with halogen substituted C Cβ alkoxy, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ Heterocycle, aryl, benzyl or heteroaryl, or is the group -NR ³ R ⁴ , -NR ³ (CO) -L, -NR ³ (CS) NR ³ R ⁴ , or R ² and R ^{5 in} common form a C ₃ -C ₆ heterocycloalkyl ring which is interrupted at least once by nitrogen and may optionally be interrupted one or more times by oxygen or sulfur and / or optionally by one or more - (CO) - or -SO ₂ - groups in Ring may be interrupted and / or optionally one or more double bonds in the ring may contain and / or the ring itself optionally one or more times, same or different with cyano, halogen, hydroxy, -CC ₆ - alkyl, C ₃ -C ₃ -cycloalkyl, -CC ₆ -hydroxyalkyl, -CC ₆ -alkoxyalkyl or with the group -NR ³ R ⁴ or -COR ⁶ may be substituted and / or with optionally mono- or polysubstituted, identically or differently with halogen, -CC ₆ -alkoxy or with the group - COR ⁶ substituted aryl or heteroaryl may be substituted,

R ³ and R ⁴ independently of one another represent hydrogen or optionally mono- or polysubstituted, identical or different, with halogen, hydroxyl, C ₃ -C ₆ -heterocycloalkyl, -CC ₆ -hydroxyalkoxy or with the group -NR ³ R ⁴ C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, -CO-C ₁ -C ₆ -alkyl or aryl, where the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C ₆ -Heterocycloalkylring itself each optionally optionally one or more times, same or different with cyano, halogen, Cι-C ₆ -alkyl, -C ₆ hydroxyalkyl, Cι-C ₆ -alkoxy, C ₃ -C ₈ cycloalkyl, or may be substituted with the group -NR ³ R ⁴ or -CO-NR ³ R ^4, or R ³ and R ⁴ together form a C ₃ -C ₆ -heterocycloalkyl ring which is interrupted at least once by nitrogen and may optionally be interrupted once or several times by oxygen or sulfur and / or optionally by one or more - (CO) - or - SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the heterocycloalkyl itself optionally one or more times, same or different with -CC ₆ alkyl, C ₃ -C ₆ - Cycloalkyl, Ci-Cβ-Hydrox yalkyl, Ci-Cβ-alkoxyalkyl, cyano, hydroxy or with the group -NR R ⁴ may be substituted, R ^{5 is} optionally mono- or polysubstituted, identical or different with halogen, hydroxy, cyano, CrC ₆ alkoxy, C ₃ - C ₆ -cycloalkyl, C ₃ - C _δ -heterocycloalkyl, or -C-C ₆ -alkyl substituted with the group -NR ³ R ^4, C ₁ -C ₆ -alkenyl, C ₁ -C ₆ -alkynyl, where the heterocycloalkyl itself is optionally may be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds in the ring may be included and wherein the C ₃ -C itself in each case optionally mono- or polysubstituted ₆ -heterocycloalkyl, identically or differently with cyano, halogen, Cι-C ₆ -alkyl, C ₆ hydroxyalkyl, Cι-C ₆ alkoxy, C ₃ -C ₆ -cycloalkyl, or may be substituted by the group -NR ³ R ⁴ or -CO-NR ³ R ⁴ , R ^{6 is} hydroxy, C ₁ -C ₆ -alkyl, CC ₆ -alkoxy or the group -NR ³ R ⁴ , R ^{7 is} - (CH ₂ ) _n -aryl or - (CH ₂ ) _n -heteroaryl and n is 1 - 6, as well as their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.

Particular preference is given to those compounds of the general formula I in which Q is phenyl, naphthyl or indolyl,

A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted by identical or different substituents with halogen, hydroxy, C ₃ -C ₆ -heterocycloalkyl or with the group -NR ³ R ⁴ or - CO (NR ³ ) -M substituted CC ₃ alkyl or CC ₆ - alkoxy, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by one or more - ( CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally one or more times, same or different with -CC ₆ alkyl, C ₃ -C ₆ cycloalkyl, Cι-C ₆ - may be substituted hydroxyalkyl or with the group -NR ³ R ⁴ or -NR ³ (CO) -L, -NR ³ (CO) -NR ³ -L, -COR ⁶ , -CO (NR ³ ) -M, - NR ³ (CS) NR ³ R ⁴ , -NR ³ SO ₂ -M, -SO ₂ -NR ³ R ⁴ or -SO ₂ (NR ³ ) -M ste hen L optionally optionally mono- or polysubstituted, identically or differently, with Ci-Cβ-hydroxyalkoxy, -CC ₆ -alkoxyalkoxy, C ₃ -C ₆ - heterocycloalkyl or with the group -NR ³ R ⁴ , substituted CC ₆ alkyl or Heteroaryl, where the heterocycloalkyl itself is optionally substituted by one or more nitrogen, oxygen and / or or sulfur atoms may be interrupted and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally mono- or polysubstituted, identically or differently, with Cι-C ₆ alkyl, C ₃ - C ₆ cycloalkyl, Ci-Ce-hydroxyalkyl, or may be substituted with the group -NR ³ R ^4, M is optionally mono- or d, C ₆ -alkyl which is mono- or disubstituted by identical or different substituents with the group -NR ³ R ⁴ or C ₃ -C ₆ -heterocycloalkyl, X is -NH- or -NR ⁵ -,

R ^{1 is} optionally mono- or polysubstituted by identical or different halogen-substituted C 1 -C 4 -alkyl, C ₃ -cycloalkyl, AHyl or propargyl,

R ² represents hydrogen or represents optionally mono- or polysubstituted, identically or differently with halogen, hydroxy, cyano, CrC ₆ - Cι-C alkyl, ₆ alkoxy, d-Ce-hydroxyalkyl, C ₃ -C ₆ cycloalkyl, C C ₃ -C ₆ -heterocycloalkyl, C ₁ -C ₆ -alkynyl, aryl, aryloxy, heteroaryl or with the group -SC C ₆ -alkyl, -COR ⁶ , -NR ³ R ⁴ , -NR ³ (CO) -L or - NR ³ COOR ⁷ substituted -CC ₆ alkyl, -CC ₆ alkoxy, CC ₆ - alkenyl, -CC ₆ alkynyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ heterocycloalkyl, aryl or heteroaryl where the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds can be contained in the ring and wherein aryl, heteroaryl, C ₃ -C ₆ -cycloalkyl and / or the C ₃ -C ₆ -heterocycloalkyl each optionally themselves one or more fa ch, identical or different with cyano, halogen, hydroxy, C -C ₆ -alkyl, C ₁ -C ₆ -hydroxyalkyl, optionally mono- or polysubstituted, identically or differently with halogen-substituted d- Cs-alkoxy, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -heterocycloalkyl, aryl, benzyl or heteroaryl may be substituted, or for the group -NR ³ R ⁴ , -NR ³ (CO) -L, -NR ³ (CS) NR ³ R ⁴ , or

R ² and R ⁵ together form a C ₃ -C ₆ heterocycloalkyl ring which is interrupted at least once by nitrogen and may optionally be interrupted once or several times by oxygen or sulfur and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally one or more times, same or different with cyano, halogen, hydroxy, C ₁ -C ₆ -alkyl, C ₃ -C ₆ cycloalkyl, Cι-C ₆ hydroxyalkyl, -C ₆ alkoxyalkyl or substituted with the group -NR ³ R ⁴ or -COR ⁶ can and / or singly with optionally one or more times, identically or differently with halogen , C ₁ -C ₆ -alkoxy or with the group - COR ⁶ -substituted aryl or heteroaryl may be substituted, R ³ and R ^{4 are} independently hydrogen or optionally mono- or polysubstituted, identical or different with halogen, H ydroxy, C ₃ -C ₆ - heterocycloalkyl Ci-Cβ-hydroxyalkoxy or substituted with the group -NR ³ R ⁴ Cι-C, ₆ alkyl, -C ₆ - alkoxy, -CO-Cι-C ₆ alkyl or aryl where the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C ₆ -Heterocycloalkylring itself each optionally optionally one or more times, same or different with cyano, halogen, -CC ₆ alkyl, C -Cβ hydroxyalkyl, -C -C ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, or may be substituted by the group -NR ³ R ⁴ or -CO-NR ³ R ⁴ , or

R ³ and R ⁴ together form a C ₃ -C ₆ -HeterocycloalkyIring which is interrupted at least once by nitrogen and may optionally be interrupted by one or more times by oxygen or sulfur and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the heterocycloalkyl ring itself optionally one or more times, same or different with -CC ₆ alkyl, C ₃ -C ₆ -cycloalkyl, C ₁ -C ₆ -hydroxyalkyl, C ₁ -C ₆ -alkoxyalkyl, cyano, hydroxy or may be substituted by the group -NR ³ R ⁴ ,

R ⁵ is optionally substituted one or more times, identically or differently with halogen, hydroxy, cyano, CrC ₆ alkoxy, C ₃ -C ₆ cycloalkyl, C ₃ - C ₆ substituted heterocycloalkyl, or with the group -NR ³ R ⁴ C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkenyl, C ₁ -C ₆ -alkynyl, where the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by an or a plurality of - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C ₆ -Heterocycloalkylring itself each optionally one or more times, the same or differently, with cyano, halogen, _Cι-C6 alkyl, CC ₆ hydroxyalkyl, Cι-C ₆ -alkoxy, C ₃ -C ₆ cycloalkyl, or with the group -NR ³ R ⁴ or -CO-NR ³ R ⁴ may be substituted

R ^{6 is} hydroxy, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy or the group -NR ³ R ⁴ , R ^{7 is} - (CH ₂ ) _n -aryl or - (CH) _n -heteroaryl and n is 1 - 6, and their solvates, hydrates, stereoisomers, diastereomers,

Enantiomers and salts. Particular preference is given to those compounds of the general formula (I) in which

Q is phenyl, naphthyl or indolyl,

A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted by identical or different substituents with pyrrolidinyl, piperidinyl, piperazinyl or C -C -substituted with the group --N (CC ₆ -alkyl) ₂ ₃ alkyl or Cι-C are ₆ alkoxy wherein pyrrolidinyl, piperidinyl or piperazinyl itself optionally substituted one or more times, identically or differently, with Cι-C ₆ alkyl or Cι-C ₆ hydroxyalkyl may be substituted, or -CO (NH) -M, -CO (NCH ₃ ) -M, -NH (CO) -L, -NH (CO) -NH-L, -SO ₂ (NH) -M or -SO ₂ (NCH ₃ ) - Stand,

L is optionally mono- or polysubstituted, identically or differently, with C ₁ -C ₆ -hydroxyalkoxy, C -C ₆ -alkoxyalkoxy, pyrrolidinyl, piperazinyl or C ₁ -C ₆ -alkyl or pyridyl which is substituted by -N (C 1 -C ₆ -alkyl) 2, where Pyrrolidinyl or piperazinyl itself may optionally be monosubstituted or polysubstituted, identically or differently, by C 1 -C 6 -alkyl,

M is optionally substituted one or more times, identically or differently, with the group -N _(Cι-C6 alkyl) ₂ or pyrrolidinyl substituted Cι ~ C ₆ - is alkyl, X is -NH- or -NR ⁵ - group,

R ^{1 represents} optionally mono- or polysubstituted by identical or different halogen-substituted C 1 -C ₄ -alkyl,

R ² represents hydrogen or represents optionally Ci-Cβ- alkyl, Cι-C ₆ -alkoxy, C one or more times, identically or differently with halogen, hydroxy, cyano, ₆ hydroxyalkyl, C ₃ -C ₆ cycloalkyl , Tetrahydrofuranyl, pyrrolidinyl, piperazinyl, morpholinyl, phenyl, phenoxy, biphenyl, naphthyl, thienyl, furanyl, tetrazolyl, pyridyl or with the group -SC-C ₁ -C ₆ -alkyl, -CONH ₂ , -COO-C ₁ -C ₆ - Alkyl, - N is CrCe-alkylh, -N (-CC ₆ -alkyl) phenyl, -NH (CO) -L substituted CVCβ-alkyl, C ₁ -C ₆ -alkenyl, C ₁ -C ₆ -alkynyl, C ₃ -C ₆ -cycloalkyl, pyrrolidinyl, piperidinyl, phenyl, tetralinyl or indolyl, wherein phenyl, furanyl, C ₃ -C ₆ -cycloalkyl, piperidinyl or piperazinyl in each case even if appropriate optionally mono- or polysubstituted, identically or differently, with C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, cyano, halogen, hydroxy, phenyl, benzyl, morpholinyl and C 1 -C ₆ -alkyl or C ₁ -C ₄ -alkyl ₆ -alkoxy itself may optionally be monosubstituted or polysubstituted by identical or different substituents with halogen, or the group -Nfd-Cβ-alkylh, -NH (CO) -L, -NCH ₃ (CS) NHCH ₃ , or R ² and R ⁵ together aziridinyl, azetidinyl, morpholinyl, pyrrolidinyl, piperidinyl or piperazinyl form, wherein aziridinyl, azetidinyl, morpholinyl, pyrrolidinyl, piperidinyl or piperazinyl itself optionally one or more times, same or different with hydroxy, C 1 -C ₆ alkyl, Ci-Ce -Hydroxyalkyl, C ₁ -C ₆ -alkoxyalkyl or with the group -CONH ₂ , -CO-C C ₆ -alkyl or -COO- dC ₆ alkyl may be substituted and / or substituted with optionally mono- or polysubstituted by identical or different substituents with halogen or C _r Cs alkoxy substituted phenyl, benzyl or pyridyl, and

R ^{5 is} optionally mono- or polysubstituted by identical or different C ₁ -C ₆ -alkoxy-substituted C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkenyl, and also their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.

Above all, preference is given to those compounds of the general formula (I) in which

Q is phenyl, naphthyl or indolyl,

A and B are independently hydrogen, halogen, hydroxy, amino or nitro or optionally mono- or polysubstituted, identically or differently, with pyrrolidinyl, piperidinyl, piperazinyl or with the group --N (CH ₃ ) ₂ -substituted C 1 -C ₃ -alkyl or C 1 -C ₃ -alkoxy, pyrrolidinyl, piperidinyl or piperazinyl itself optionally being or polysubstituted, identically or differently, with C ₁ -C ₃ -alkyl or C ₁ -C ₃ -hydroxyalkyl, or for the group -CO-NH- (CH ₂ ) ₂ -N (CH ₃ ) ₂ , -CO-NH- ( CH ₂ ) ₂ - N (C ₂ H ₅ ) ₂ , -CO-N (CH ₃ ) - (CH ₂ ) ₂ -N (CH ₃ ) ₂ ,

-NH (CO) -C (CH ₃ ) ₃ , -NH (CO) - (CH ₂ ) -O (CH ₂ ) ₂ -OCH ₃ , -NH (CO) - (CH ₂ ) ₂ -N (C ₂ H ₅ ) ₂ ,

or -SO ₂ -NH- (CH ₂ ) ₂ -N (CH ₃ ) ₂ or -SO ₂ -N (CH ₃ ) - (CH ₂ ) ₂ -N (CH ₃ ) ₂ , X is -NH- or - NR ⁶ - stands,

R ^{1 represents} optionally mono- or polysubstituted by identical or different halogen-substituted C ₁ -C ₃ -alkyl, represents hydrogen or optionally mono- or polysubstituted, identical or different, with halogen, hydroxyl, cyano, C 1 -C ₆ -alkyl, C ₆ -hydroxyalkyl, methoxy, C ₃ -C ₆ -cycloalkyl, tetrahydrofuranyl, pyrrolidinyl, piperazinyl, morpholinyl, phenyl, phenoxy, biphenyl, naphthyl, thienyl, furanyl, tetrazolyl or pyridyl or with the group -S-CH ₃₎ -COOCH ₃ , -COOC ₂ H ₅ , -CO-NH ₂ , -OCF ₃ , - N (CH ₃ ) -phenyl, -N (C ₁ -C 12 -alkyl) _{2 L} -NH (CO) -CH ₃ -substituted C i -

Cβ-alkyl, -CC-alkenyl, -CC ₄ alkynyl, C ₃ -C ₆ -cycloalkyl, piperidinyl, phenyl, pyrolidinyl, indolyl or tetralinyl, where phenyl, furanyl, C ₃ -C ₆ cycloalkyl, piperidinyl or piperazinyl optionally each themselves one or more times, identically or differently with cyano, halogen, hydroxy, C ₁ -C ₃ -alkyl, C ₁ -C ₃ -

Hydroxyalkyl, methoxy, morpholinyl, phenyl or benzyl, or for the group -N (CH ₃ ) ₂ , -N (CH ₃ ) (CS) NHCH ₃ , -NH (CO) -CH ₃ , - NH (CO) Pyridyl, -NH (CO) pyridinyl, or

R ² and R ⁵ together form one of the following rings

and

R ^{5 represents} optionally mono- or polysubstituted, identically or differently with dC ₆ -alkoxy-substituted dC ₃ -alkyl or dC ₃ -alkenyl, and their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.

The place marked with * in the form indicates the linkage point to the remainder of the formula.

Likewise provided by the invention are compounds of the general formula I in which

Q represents phenyl, naphthyl, quinolinyl, benzimidazolyl, indolyl, indazolyl, thiazolyl, imidazolyl or pyridyl, A and B independently of one another represent hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted, identically or differently, with hydroxyl , C ₃ -C ₆ -heterocycloalkyl or -NR ³ R ⁴ or -CO (NR ³ ) (CH ₂ ) _n NR ³ R ⁴ -substituted dC ₃ -alkyl or dC ₆ -alkoxy, the heterocycloalkyl itself being optionally may be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds in the ring may be contained and / or the ring itself may optionally be mono- or polysubstituted, identically or differently with C -C ₆ alkyl, C ₃ -Cβ-cycloalkyl, Ci-Cβ-hydroxyalkyl or with the group -NR ³ R ⁴ may be substituted , or for COR ⁶ , -CO (NR ³ ) (CH ₂ ) _n NR ³ R ⁴ , -NR ³ (CO) -CC ₆ -alkyl, - NR ³ (CO) (CH ₂ ) _n -C 1 -C ₆ -alkoxy, -NR ³ (CO) (CH ₂ ) _{n is} C ₁ -C ₆ alkoxyalkoxy, - NR ³ (CO) (CH ₂ ) _n NR ³ R ⁴ , -NR ³ (CO) NR ³ R ⁴ , -NR ³ (CS) NR ³ R ⁴ , -NR ³ SO ₂ -Ci-Ce-alkyl, -NR ³ SO ₂ - (CH ₂ ) _n NR ³ R ⁴ , -SO ₂ -NR ³ R ⁴ or -SO ₂ (NR ³ ) (CH ₂ ) _n NR ³ R ⁴ stand .

X is oxygen, -NH- or -NR ⁵ -,

R ^{1 represents} optionally mono- or polysubstituted by identical or different halogen-substituted C ₁ -C ₃ -alkyl, C ₃ -cycloalkyl, allyl or propargyl, R ² is hydrogen or mono- or optionally me rfach, identically or differently with halogen, hydroxy, cyano, dC ₆ alkyl, d-Cβ-alkoxy, d-Cβ hydroxyalkyl, C -C ₆ cycloalkyl, C ₃ -C ₆ - heterocycloalkyl, aryl, heteroaryl or with the group -S-C ₁ -C ⁶ -alkyl, -COR ⁶ , -NR ³ R ⁴ , -NR ³ (CO) -C 1 -C ₆ -alkyl, -NR ³ (CO) -aryl, -NR ³ (CO) -Heteroaryl, -NR ³ COOR ⁷ , -NR ³ (CS) NR ³ R ⁴ substituted C 1 -C ₆ -alkyl, C 1 -C ₆ -alkoxy, C -C ₆ -alkenyl, C i -Cβ-alkynyl, Cs-Cβ-cycloalkyl, C ₃ -C ₆ -heterocycloalkyl, aryl or heteroaryl, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -Cβ-cycloalkyl and / or C ₃ -C ₆ - Heterocycloalkylring itself each optionally one - or more times, identically or differently, with cyano, halogen, d-Cβ-alkyl, Cι-C ₆ hydroxyalkyl, Ci-Cβ alkoxy, C ₃ -C ₆ cycloalkyl, or with the group -NR ³ R ⁴ or - CO-NR ³ R ⁴ or the group -NR ³ R ⁴ , -NR ³ (CO) -aryl, -NR ³ (CO) -eteroaryl, -NR ³ (CS) NR ³ R ⁴ , or R ² and R ⁵ together form a C ₃ -C ₆ heterocycIoalkyl ring which is interrupted at least once by nitrogen and may optionally be interrupted one or more times by oxygen or sulfur and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more Doppelbindu lengths may be contained in the ring and / or the ring itself optionally one or more times, same or different with cyano, halogen, hydroxy, -CC _6- alkyl, Cs-Cβ-cycloalkyl, C ₁ -C ₆ -hydroxyalkyl, C ₁ -C ₆ -alkoxyalkyl, aryl or may be substituted by the group -NR R ⁴ , R ³ and R ⁴ independently of one another represent hydrogen or optionally mono- or polysubstituted, identical or different, with halogen, hydroxyl, C ₃ -C ₆ -heterocycloalkyl, -CC ₆ -hydroxyalkoxy or with the group -NR ³ R ⁴ Ci-Cβ-alkyl, dC ₆ - alkoxy or -CO-Ci-Cβ-alkyl, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C ₆ -Heterocycloalkylring itself each optionally one or more times, the same or different m it cyano, halo, Cι-C ₆ -alkyl, C ₈ hydroxyalkyl, Ci-Cβ alkoxy, C ₃ -C ₆ cycloalkyl, or with the group -NR ³ R ⁴ or NR ³ -CO- R ⁴ may be substituted, or R ³ and R ⁴ together form a C ₃ -Cβ heterocycloalkyl ring s, which is interrupted at least once by nitrogen and may optionally be interrupted by one or more times by oxygen or sulfur and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds in the ring may be included and / or self optionally mono- the heterocycloalkyl or more times, identically or differently, with Cι-C ₆ alkyl, C ₃ -C ₆ - cycloalkyl, dC ₆ hydroxyalkyl, Cι-C ₆ - Alkoxyalkyl, cyano, hydroxy or with the group -NR ³ R ⁴ may be substituted,

R ⁵ is optionally substituted one or more times, identically or differently with halogen, hydroxy, cyano, dC ₆ alkoxy, C ₃ -Cβ cycloalkyl, C ₃ -C ₆ - heterocycloalkyl, or substituted with the group -NR ³ R ⁴ C -Cβ-alkyl, Ci-Cβ-alkenyl, Ci-Cβ-alkynyl, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by one or more - (CO ) - or -SO ₂ - Groups may be interrupted in the ring and / or optionally one or more double bonds in the ring may be contained and wherein the C ₃ -C ₆ -Heterocycloalkylring itself each optionally one or more times, same or different with cyano, halogen, C ₁ -C ₆ -alkyl , C ₁ -C ₆ -hydroxyalkyl, C -C ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, or may be substituted by the group -NR ³ R ⁴ or -CO-NR ³ R ⁴ , R ^{6 is} hydroxyl, C ₁ -C ₄ -alkyl, Alkyl, C 1 -C 6 -alkoxy or the group -NR ³ R ⁴ ,

R ^{7 is} - (CH ₂ ) _n -aryl or - (CH ₂ ) _n -heteroaryl and _{n is} 1-6, and their stereoisomers, diastereomers, enantiomers and salts.

Particular preference is given to those compounds of the general formula I in which

Q is phenyl, naphthyl, quinolinyl, benzimidazolyl or indolyl,

A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted, identically or differently, with hydroxyl, pyrrolidinyl, piperidinyl, piperazinyl or with the group --N (CH ₃ ) ₂ , --N ( C ₂ H ₅ ) ₂ or -CO (NH) (CH ₂ ) ₂ N (C ₂ H ₅ ) ₂ substituted C ₁ -C ₃ -alkyl or C ₁ -C ₃ -alkoxy, where pyrrolidinyl, piperidinyl or piperazinyl itself optionally - or more times, identically or differently, with Cι-C ₃ alkyl, C ₃ -C ₆ cycloalkyl, -C ₃ - hydroxyalkyl or may be substituted with the group -N (C ₂ H ₅₎ _2, or for the group COOH, -COOCH ₃ , -COOC ₂ H ₅ , -CONH ₂ ,

-NH (CO) -C (CH ₃ ) ₃ , -NH (CO) - (CH ₂ ) -OCH ₃ , -NH (CO) - (CH ₂ ) ₂ -OCH ₃ , NH (CO) - (CH ₂ ) -O (CH ₂ ) ₂ -OCH ₃ , -NH (CO) - (CH ₂ ) ₂ -N (C ₂ H ₅ ) ₂ ,

-NH (CO) -NH (CH ₂ ) ₂ -N (CH ₃ ) _{2 L} -NH (CO) -NH (CH ₂ ) ₂ -OH, -NH (CO) -NH (CH ₂ ) ₂ -O (CH ₂ ) ₂ -OH,

-NH (CS) NH (CH ₂ ) ₂ -OH, -NH (CS) NH (CH ₂ ) ₂ -O (CH ₂ ) ₂ -OH,

-NHSO ₂ -C 1 -C ₆ -alkyl, -NHSO ₂ -CH ₃ ,

or -SO ₂ -NH- (CO) -CH ₃ ,

X is oxygen, -NH- or -NR ⁵ -,

R ^{1 is} optionally mono- or polysubstituted by identical or different fluorine, chlorine, bromine or iodine, C ₁ -C ₃ -alkyl or C ₃ -cycloalkyl,

R ² is optionally substituted one or more times, identically or differently, by fluorine, chlorine, bromine, iodine, hydroxy, cyano, C ₆ -alkyl, C ₆ - hydroxyalkyl, methoxy, or with the group -S-CH _3, -COOCH ₃ , COOC ₂ H ₅ , -NH (CH ₃ ), -N (CH ₃ ) ₂ , -NHC (CH ₃ ) ₃ , -NH (CO) -CH ₃ , -NH (CO) -phenyl, - NH (CO) -O- (CH ₂ ) -phenyl, -N (CH ₃ ) - (CS) -NH (CH ₃ ), -N (CH ₃ ) - (CS) -N (CH ₃ ) ₂ or with the following ring systems C ₃ -C ₈ -cycloalkyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, phenyl, biphenyl, furanyl, thienyl, pyrrolyl, pyridyl, these ring systems optionally each themselves one or more times, identically or differently, with -CC ₃ -alkyl, Cyano, fluorine, chlorine, bromine, iodine, methoxy or -CO-NH ₂ may be substituted, substituted Ci-Cs-alkyl, -CC ₃ -alkoxy, Ci-Cs-alkenyl, dC ₃ - alkynyl, C ₃ -C ₆ -cycloalkyl, isoxazolyl, piperidinyl, phenyl, pyrazolyl, pyrrolyl, (tetralin) yl or thiazolyl, or for the group -N (CH ₃ ) ₂ , -N (CH ₃ ) (CS) NHCH ₃ , -NH (CS) N (CH ₃ ) ₂ , - NH (CO) -phenyl, -NH- (CH ₂ ) -CF ₃ , -NH- (CH ₂ ) ₂ -CF _3, -NH- (CH ₂ ) ₂ -OH, NH (CO) -pyridinyl,

or R ² and R ⁵ together form one of the following rings

- ^ - N

of the and R ⁵ is optionally substituted one or more times, identically or differently with halogen, hydroxy, cyano, C ₆ -alkoxy, C ₃ -C ₆ cycloalkyl, C ₃ -C6- heterocycloalkyl, or with the group -N (CH ₃ ) ₂ substituted d-Cs-alkyl, Ci-Cs-alkenyl, -C-C ₃ -alkynyl, and their stereoisomers, diastereomers, enantiomers and

Salts.

Another object of the present invention are compounds of general formula IA

in the

Q is aryl or heteroaryl,

A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted by identical or different substituents with halogen, hydroxy, C ₃ -C ₆ -heterocycloalkyl or with the group -NR ³ R ⁴ or - CO (NR ³ ) -M substituted dC ₃ alkyl or -C-C ₆ alkoxy, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally one or more times, same or different with Ci-Cβ-alkyl , C ₃ -Ce -cycloalkyl, C may be C 6 -hydroxyalkyl or may be substituted by the group -NR ³ R ⁴ , or -NR ³ (CO) -L, -NR ³ (CO) -NR ³ -L, -COR ⁶ , -CO (NR ³ ) -M, -NR ³ (CS) NR ³ R ⁴ , -NR ³ SO ₂ -M, -SO ₂ -NR ³ R ⁴ or -SO ₂ (NR ³ ) -M, L is optionally mono- or polysubstituted, identically or differently, by C -Cβ-hydroxyalkoxy, C ₁ -C ₆ -alkoxyalkoxy, C ₃ -C ₆ -heterocycloalkyl or by the group -NR ³ R ⁴ , substituted C ₁ -C ₆ -alkyl or heteroaryl, where Heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more ring double bonds can be contained and / or the ring itself optionally substituted one or more times, identically or differently, with Cι-C ₆ alkyl, C ₃ -C ₆ cycloalkyl, Cι-C ₆ hydroxyalkyl or with the group -NR ³ R may be substituted ^4, may be single or M is optionally more times, identically or differently, with the group -NR ³ R ⁴ or C ₃ -C ₆ heterocycloalkyl substituted Cι-C ₆ -alkyl, R ¹ is optionally mono- or several times, the same or different with Haloge n is substituted C ₁ -C ₄ -alkyl, C ₃ -cycloalkyl, allyl or propargyl, R ^{2a is} allyl or propargyl,

R ³ and R ⁴ independently of one another are hydrogen or optionally mono- or polysubstituted, identically or differently, by halogen, hydroxyl, C ₃ -Ce-heterocycloalkyl, C ₁ -C -hydroxyalkoxy or C ₁ -C ₆ -substituted with the group -NR ³ R ⁴ Alkyl, C ₁ -C ₆ -alkoxy, -CO-C ₁ -C ₆ -alkyl or aryl, where the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by an or a plurality of - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C ₆ -Heterocycloalkylring itself each optionally one or more times, the same or may be substituted by cyano, halogen, C 1 -C ₆ -alkyl, C 1 -C ₆ -hydroxyalkyl, C 1 -C ₆ -alkoxy, C 5 -C 8 -cycloalkyl, or by the group -NR ³ R ⁴ or -CO-NR ³ R ⁴ , or R ³ and R ⁴ together form a C ₃ -C ₆ -heterocycloalkyl ring which is interrupted at least once by nitrogen and may optionally be interrupted by one or more times by oxygen or sulfur and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the heterocycloalkyl ring itself optionally one or more times, same or different with d-Cβ-alkyl, C ₃ -C ₆ -Cycloalkyl, Cr Cβ-hydroxyalkyl, -CC ₆ -alkoxyalkyl, cyano, hydroxy or may be substituted by the group -NR ³ R ⁴ , and

R ^{6 is} hydroxy, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy or the group -NR ³ R ⁴ , and also their solvates, hydrates, stereoisomers, diastereomers,

Enantiomers and salts.

These compounds have an allyl ester or propargyl ester in contrast to the compounds of general formula I. These too

Compounds inhibit kinases of the polo family and, in particular by the presence of the allyl ester, are more suitable for cleavage into the free acid and thus for the preparation of compounds of the general type

Formula I.

Preference is given to those compounds of the general formula IA in which

Q is phenyl, quinolinyl, indolyl or naphthyl,

A and B independently of one another are hydrogen or halogen or optionally mono- or polysubstituted, identical or different, with halogen, hydroxyl or with the group -NC Cβ-alkyl) ₂ or -CO (NH) -M-substituted C -C ₃ - Alkyl or C ₁ -C ₆ -alkoxy or -NH (CO) -L, -NH (CO) -NH-L, -COR ⁶ , -CO (NH) -M, -CO (NCH ₃ ) -M, -SO ₂ (NH) -M or -SO ₂ (NCH ₃ ) -M,

L is optionally mono- or polysubstituted by identical or different pyrrolidinyl-substituted -CC ₆ alkyl,

M ₆ alkyl optionally mono- or polysubstituted, identically or differently, with the group -N (dC ₆ alkyl) ₂ or pyrrolidinyl substituted CrC, R ^{1 is} C ¹ -C ₃ -alkyl,

R ^{2a is} allyl or propargyl and

R ^{6 is} hydroxy, C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkoxy, and also their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.

In particular, compounds of the compounds of Preparation Examples 77, 104, 105, 106, 107, 117, 119, 121, 123-131, 133, 135, 137, 140 are preferred.

Another object of the invention are the preparation examples 1 to 75, and their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts. These compounds differ from those of general formula I by the presence of an ester residue, rather than an amide bond. These compounds are suitable for inhibiting kinases of the polo family. These compounds are also known as

Intermediates suitable for the preparation of the compounds of general formula I.

Essential features of the compounds of the invention are in particular R ¹ as optionally substituted with halogen -CC-alkyl

or C ₃ -cycloalkyl, and the secondary amine on Q represents.

Further objects of the invention are in particular also those uses of the compounds of general formulas IIA, IIB, INA, IIIB, IVA, IVB and compounds of the general V, as intermediates for the preparation of the compounds of general formula I. Uses of the compounds of the general formulas IIA or IIB

in which D is the group -NO ₂ , -NH ₂ or -NH (CO) OC (CH ₃ ) ₃ and E is -CC ₆ - alkoxy or halogen and R ³ and R ^{4 are} those described in the general formula I. Have significance as intermediates for the preparation of the compounds of general formula I.

Uses of the compounds of the general formulas INA or IIIB

in which D is the group -NO ₂ , -NH ₂ or -NH (CO) OC (CH ₃ ) ₃ and G is the group -NR ³ R ⁴ and R ³ , R ⁴ and n are those represented by the general formula I have described meaning as intermediates for the preparation of the substances of the general formula I.

Uses of the compounds of general formulas IVA or IVB

in which D for the group -NO ₂ , -NH ₂ or -NH (CO) OC (CH ₃ ) ₃ and K for optionally substituted by the group -NR ³ R ⁴ -CC ₆ alkyl or dC ₆ - alkenyl and L is optionally substituted by -CC ₆ alkoxy, -C-Cβ-alkoxy-Cι-Cβ-alkoxy or the group -NR ³ R ^{4 is} substituted dC ₆ alkyl or Ci-Cβ-alkenyl and R ³ and R ⁴ in the general formula I described have, as intermediates for the preparation of the substances of general formula I.

Compounds of the general formula V

^V in which Q, A, B and R ^{1 have} the meaning described in general formula I as intermediates for the preparation of the compounds of the general formula I according to the invention, provided that cyano- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) - ylidenes] -acetic acid does not fall under the general formula V:

For the use of the compounds of the general formula I according to the invention as pharmaceuticals, these are brought into the form of a pharmaceutical preparation which, in addition to the active substance for enteral or parenteral administration, is suitable pharmaceutical, organic or inorganic inert carrier materials, such as, for example, water, gelatin, gum arabic , Lactose, starch, magnesium stearate, talc, vegetable oils, polyalkylene glycols, etc. The pharmaceutical preparations may be in solid form, for example as tablets, dragees, suppositories, capsules or in liquid form, for example as solutions, suspensions or emulsions. If appropriate, they also contain adjuvants, such as preservatives, stabilizers, wetting agents or emulsifiers; Salts for changing the osmotic pressure or buffer. These pharmaceutical preparations are also the subject of the present invention.

Injection solutions or suspensions, in particular aqueous solutions of the active compounds in polyhydroxyethoxylated castor oil, are particularly suitable for parenteral use. Surfactant auxiliaries such as salts of bile acids or animal or plant phospholipids, but also mixtures thereof and liposomes or components thereof can also be used as carrier systems.

For oral administration, especially tablets, dragees or capsules with talc and / or hydrocarbon carriers or binders, such as lactose, corn or potato starch, are suitable. The application can also take place in liquid form, for example as juice, which may be accompanied by a sweetener.

The enteral, parenteral and oral applications are also the subject of the present invention.

The dosage of the active ingredients may vary depending on the route of administration, the age and weight of the patient, the nature and severity of the disease being treated, and similar factors. The daily dose is 0.5-1000 mg, preferably 50-200 mg, which dose may be given as a single dose to be administered once or divided into 2 or more daily doses.

Likewise provided by the present invention is the use of the compounds of general formula I for the preparation of a medicament for the treatment of cancer, autoimmune diseases, cardiovascular diseases, chemotherapeutic-induced alopecia and mucositis, infectious diseases, nephrological diseases, chronic and acute neurodegenerative diseases and viral infections , Cancerous tumors and leukemia, autoimmune psoriasis, alopecia and multiple sclerosis, cardiovascular diseases, stenosis, arteriosclerosis and restenosis, infectious diseases caused by unicellular parasites, nephrology glomerulonephritis, chronic neurodegenerative diseases Huntington's disease, amyotrophic lateral sclerosis , Parkinson's disease, AIDS dementia and Alzheimer's disease, brain ischemia in acute neurodegenerative diseases and neurotrauma, and viral infections are cytomegalovirus infections, herpes, hepatitis B or C, and HIV disorders. Likewise provided by the present invention are medicaments for the treatment of the abovementioned disorders which contain at least one compound according to the general formula I, as well as medicaments with suitable formulation and carrier substances.

The compounds of the general formula I according to the invention are, inter alia, excellent inhibitors of the polo-like kinases, such as Plk1, Plk2, Plk3 and Plk4.

Unless the preparation of the starting compounds is described, they are known or can be prepared analogously to known compounds or processes described herein. It is also possible to carry out all the reactions described here in parallel reactors or by combinatorial working techniques. The isomer mixtures can be prepared by conventional methods such as crystallization, chromatography or salt formation in the isomers, such as. B. are separated into the enantiomers, diastereomers or E / Z isomers, provided that the isomers are not in equilibrium with each other.

The preparation of the salts is carried out in a customary manner by adding a solution of the compound of formula I with the equivalent amount or an excess of a base or acid, optionally in solution, and separating the precipitate or working up the solution in a conventional manner.

Preparation of the compounds of the invention

The following examples illustrate the preparation of the compounds of the invention without limiting the scope of the claimed compounds to these examples.

The compounds of the general formula I or IA according to the invention can be prepared by the following general procedure scheme:

Synthesis scheme:

, sx

Coupling for reaction of A or B = amino group amino

R ^A = ethyl, propyl, allyl, benzyl R ¹ , R ² , A, B and Q have the meaning given in the general formula I. Scheme No. 1 for the synthesis of anilines:

reduction

Wherein A, Q, R ³ and R ^{4 have} the meaning given in the general formula I.

Scheme 2 for the synthesis of anilines:

reduction

Wherein A, Q, R ³ and R ^{4 have} the meaning given in the general formula I.

HR ³ R ⁴ N - ^ - ~ _s _-N. .NH ₂ OO Where A, Q, R ³ and R ^{4 have} the meaning given in the general formula I.

Scheme 4 for the synthesis of anilines:

_{O MO M}

"

Wherein A, Q, R ³ and R ^{4 have} the meaning given in the general formula I.

Scheme 5 for the synthesis of anilines:

Wherein A, Q, R ³ and R ^{4 have} the meaning given in the general formula I.

Scheme 6 for the synthesis of anilines:

Wherein A, Q, R ³ and R ^{4 have} the meaning given in the general formula I.

Scheme 7 for the synthesis of anilines:

₂ ^N / YV ^'NH 2 reagent

R ^κ = C ¹ - C ⁶ alkyl or - (CH ₂₎ _n C i - C ₆ - alkoxy, or - (CH ₂₎ _n d - C ₆ - alkoxyalkoxy

Wherein A, Q, R ³ and R ^{4 have} the meaning given in the general formula I.

Scheme 8 for the synthesis of anilines:

RL - c ¹ - C ⁶ alkyl

Wherein A and Q have the meaning given in the general formula I. Scheme 9 for the synthesis of anilines:

HNR ³ R ⁴ reduction

Wherein A, Q, R ³ and R ^{4 have} the meaning given in the general formula I.

Scheme No. 10 for the synthesis of anilines:

reduction

Wherein A, Q, R and R have the meaning given in the general formula I.

Scheme 11 for the synthesis of anilines:

^HO

Wherein A, Q, R j3 and R have the meaning given in the general formula I. Scheme 12 for the synthesis of anilines:

R ^ OH H, N -..- .. NH, ° _{. R} κ H y _ ^RN γ ^NHa A coupling O ² reagent

R ^κ = C ¹ - C ⁶ alkyl or - (CH ₂₎ _n C i - C ₆ - alkoxy, or - (CH ₂₎ _π Ci - C ₆ - alkoxyalkoxy where A and Q have the meaning given in general formula I.

Scheme No. 13 for the synthesis of anilines:

Reduction _H0 / F ^A

Wherein A and Q have the meaning given in the general formula I.

Scheme 14 for the synthesis of anilines:

reduction

R ^κ = C ¹ - C ⁶ alkyl or - the meaning given in general formula I alkoxyalkoxy wherein A, Q and R ³ - (CH ₂₎ _n C i - C _β - alkoxy, or - (CH ₂₎ _n d - C ₆ to have. Synthesis of intermediates

Preparation of the intermediates (INT) which can preferably be used for the preparation of the thiazolidinone compounds according to the invention.

Example INT1 N- (3-amino-phenyl) -2,2-dimethyl-propionamide 5.0 g of the 1,3-diaminobenzene are dissolved in 50 ml of dichloromethane and mixed at 0 ° C. with 24 ml of diisopropylethylamine and 10.4 ml of pivalic anhydride. It is stirred for 2 hours at 0 ° C and 18 hours at room temperature. The reaction mixture is mixed with half-saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic solution is washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and, after purification by chromatography on silica gel, 5.7 g of the title compound are obtained.

1 H-NMR (DMSO-d6): δ = 1.20 (s, 9H); 4.98 (s, 2H); 6.24 (d, 1H); 6.70 (d, 1H); 6.83-6.96 (m, 2H) ppm.

Example INT2 1- (2-iodo-ethyl) -4-nitrobenzenes

15 g of 4-nitrophenylethanol, 28.1 g of triphenylphosphine and 9.2 g of imidazole are dissolved in 500 ml of THF, treated in portions with 27.77 g of iodine and stirred for 2 hours at room temperature. The reaction mixture is treated with ammonium chloride solution and extracted with dichloromethane. The organic phase is washed successively with sodium thiosulfate solution and water and dried over sodium sulfate. After purification by chromatography on silica gel, 23.22 g of the title compound are obtained. 1 H-NMR (DMSO-d6): δ = 3.30 (t, 2H); 3.54 (t, 2H); 7.57 (d, 2H); 8.18 (d, 2H) ppm. Example INT3 1- [2- (4-nitro-phenyl) -ethyl] -pyrrolidines

8 g of the compound described under example INT2), 26.4 g of potassium carbonate and 3.6 ml of pyrolidine are dissolved in 20 ml of DMF and stirred at room temperature for 5 hours. The solvent is condensed off in a high vacuum, the residue is taken up in ethyl acetate and washed three times with water. The organic phase is dried over sodium sulfate. After purification by chromatography on silica gel, 5.6 g of the title compound are obtained. 1 H-NMR (DMSO-d6): δ = 1.68 (m, 4H); 2.48 (m, 4H); 2.67 (t, 2H); 2.89 (t, 2H); 7.52 (d, 2H); 8.13 (d, 2H) ppm.

Example INT4 4- (2-pyrrolidin-1-yl-ethyl) -phenylamine

5.67 g of the compound described under Example INT3) are dissolved in 500 ml of ethanol and treated with 1 g of palladium on carbon (10%). It is stirred for 2 hours under a hydrogen atmosphere at room temperature. After filtration through diatomaceous earth and condensing off the solvent on a rotary evaporator, 4.8 g of the title compound are obtained.

1 H-NMR (DMSO-d6): δ = 1.67 (m, 4H); 2.31-2.60 (m, 8H); 4.81 (s, 2H); 6.48 (d, 2H); 6.84 (d, 2H) ppm.

Example INT5 1-ethyl-4- [2- (4-nitro-phenyl) -ethyl] -piperazine

5 g of the compound described under Example INT2), 6.2 ml of triethylamine and 2.4 ml of N-methylpiperazine are dissolved in 20 ml of tetrahydrofuran and 3 hours under

Stirred reflux. A further 0.6 ml of N-methylpiperazine are added and stirring is continued for a further 3 hours under reflux. The solvent is dissolved on Condensed off rotary evaporator, the residue is taken up in ethyl acetate and washed with water. The organic phase is dried over sodium sulfate. After purification by chromatography on silica gel, 1.6 g of the title compound are obtained. 1 H-NMR (DMSO-d6): δ = 2.13 (s, 3H); 2.20-2.48 (m, 8H); 2.54 (t, 2H); 2.87 (t, 2H); 7.51 (d, 2H); 8.13 (d, 2H) ppm.

Example INT6 4- [2- (4-Methyl-piperazin-1-yl) -ethyl] -phenylamine

dissolved and treated with 1.1 g of palladium on charcoal (10%). It is stirred for 2 hours under a hydrogen atmosphere at room temperature. After filtration through diatomaceous earth and condensing off the solvent on a rotary evaporator, 5.6 g of the title compound are obtained.

1 H-NMR (DMSO-d6): δ = 2.15 (s, 3H); 2.20-2.59 (m, 12H); 4.80 (s, 2H); 6.48 (d, 2H); 6.83 (d, 2H) ppm.

Example INT7 {1- [2- (4-nitro-phenyl) -ethyl] -piperidin-4-yl} -methanol

8 g of the compound described under Example INT2), 26.4 g of potassium carbonate and 5.0 g of 4-hydroxymethylpiperidine are dissolved in 20 ml of DMF and stirred for 18 hours at room temperature. The solvent is condensed off in a high vacuum, the residue is taken up in ethyl acetate and washed three times with water. The organic phase is dried over sodium sulfate. After purification by chromatography on silica gel, 5.56 g of the title compound are obtained.

1 H-NMR (DMSO-d6): δ = 0.99-1, 16 (m, 2H); 1, 21-1,41 (m, 1H); 1.61 (d, 2H); 1, 90 (t, 2H); 2.54 (t, 2H); 2.81-2.98 (m, 4H); 3.23 (d, 2H); 4.40 (s, 1H); 7.50 (d, 2H); 8.13 (d, 2H) ppm. Example INT8 {1- [2- (4-Amino-phenyl) -ethyl] -piperidin-4-yl} -methanol

6.56 g of the compound described under Example INT7) are dissolved in 500 ml of ethanol and treated with 1, 1 g of palladium on carbon (10%). It is stirred for 4 hours under a hydrogen atmosphere at room temperature. After filtration through diatomaceous earth and condensing off the solvent on a rotary evaporator 4.67 g of the title compound are obtained.

1 H-NMR (DMSO-d6): δ = 0.99-1.20 (m, 2H); 1, 20-1, 41 (m, 1H); 1, 61 (d, 2H); 1, 87 (t, 2H); 2.36 (t, 2H); 2.50-2.60 (m, 2H); 2.88 (d, 2H); 3.23 (t, 2H); 4.40 (s, 1H); 4.80 (s, 2H); 6.47 (d, 2H); 6.84 (d, 2H) ppm.

acid tert-butyl ester

2.0 g of (4-aminophenyl) -carbamic acid (tert) butyl ester are dissolved in 60 ml of tetrahydrofuran, with 6.74 ml of triethylamine and with 1.0 ml

2-Chlorethansulfonsäurechlorid added and stirred for 2 hours at room temperature.

The reaction mixture is treated with water and extracted with ethyl acetate. The organic solution is washed successively with 4 normal hydrochloric acid, with half-saturated sodium bicarbonate solution and with saturated sodium chloride solution, dried over sodium sulfate, concentrated and after recrystallization from ethanol / dichloromethane (1: 3) 1.45 g of

Title compound obtained.

1 H-NMR (DMSO-d6): δ = 1.47 (s, 9H); 5.97 (d, 1H); 6.01 (d, 1H); 6.70 (dd, 1H); 7.03

(d, 2H); 7.35 (d, 2H); 9.28 (s, 1H); 9.70 (s, 1H) ppm. Example INT10

[4- (2-morpholin-4-yl-ethanesulfonylamino) -phenyl] -carbamic acid tert-butyl ester

107 mg of the compound described under example INT9) are dissolved in 5 ml of tetrahydrofuran, admixed with 0.25 ml of triethylamine and 71 μl of morpholine and stirred at reflux for 24 hours. The reaction mixture is treated with water and extracted with ethyl acetate. The organic solution is washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and, after purification by chromatography on silica gel, 62 mg of the title compound are obtained.

1 H-NMR (DMSO-d6, stored over K 2 CO 3): δ = 1.47 (s, 9H); 2.30 (m, 4H); 2.63 (t, 2H); 3.14 (t, 2H); 3.50 (m, 4H); 7.08 (d, 2H); 7.37 (d, 2H); 9.25 (s, 1H); 9.52 (s, 1H) ppm.

acid tert-butyl ester 200 mg of (4-aminophenyl) -carbamic acid (tert) butyl ester are dissolved in 5 ml of tetrahydrofuran, combined with 0.63 ml of triethylamine and 0.16 ml of methoxyacetyl chloride and stirred for 2 hours at room temperature. The reaction mixture is mixed with half-saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic solution is washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and, after purification by chromatography on silica gel, 211 mg of the title compound are obtained.

1 H-NMR (DMSO-d6, stored over K 2 CO 3): δ = 1.48 (s, 9H); 3.38 (s, 3H); 3.97 (s, 2H); 7.37 (d, 2H); 7.52 (d, 2H); 9.25 (s, 1H); 9.61 (s, 1H) ppm. Example INT12) N- (4-nitrophenyl) -acrylamϊd

To a solution of 20 g of 4-nitroaniline in 200 ml of THF are first added 61 ml of triethylamine and then 14.6 ml of acrylic acid chloride. The mixture is stirred for 4 h at room temperature, treated with sodium chloride solution and extracted with ethyl acetate. The crude product obtained after evaporation of the solvent is recrystallized (dichloromethane). There are obtained 18.5 g of the title compound.

¹ H-NMR (CDCl ₃ ): δ = 5.87 (1H); 6.34 (1H); 6.47 (1H); 7.92 (2H); 8.23 (2H) ppm.

Example INT13) 3- (4-Methylpiperazin-1-yl) -N- (4-nitro-phenyl) -propionamide

To a solution of 8.6 g of N- (4-nitrophenyl) acrylamide in 225 ml of THF are first added 31.2 ml of triethylamine and then 11.7 ml of 1-methylpiperazine. The mixture is stirred for 15 h under reflux and concentrated on a rotary evaporator to dryness. After addition of dichloromethane is extracted with sodium bicarbonate solution and sodium chloride solution, dried over sodium sulfate and the solvent evaporated. The crude product obtained is recrystallized (ethyl acetate). There are obtained 8.0 g of the title compound. Molecular weight = 292,341; MS (ESI): [M + 1] + = 293. Example INT14) N- (4-amino-phenyl) -3- (4-methylpiperazin-1-yl) -propionamide

A mixture of 8.6 g of N- (4-nitrophenyl) acrylamide and 0.8 g of palladium on carbon (10%) in 150 mL of ethanol was stirred in a hydrogen atmosphere for 5 h at room temperature. Subsequently, the mixture was filtered through Celite and the solvent evaporated. There was obtained 7.0 g of the title compound. ¹ H-NMR (CDCl ₃ ): δ = 2, 14 (3H); 2.19-2.52 (10H) 2.58 (2H); 4.92 (2H); 6.71 (2H); 7.05 (2H); 7.83 (1H); ppm.

Example INT15 N- (3-nitro-phenyl) -acrylamide Analogously to Example INT12) are from 20 g of 3-nitroaniline, 61 mL of triethylamine and

14.6 mL of acrylic acid chloride, after purification by recrystallization from

Dichloromethane 18.5 g of the title compound. 1 H-NMR (DMSO-d6): δ = 5.84 (dd, 1H); 6.32 (dd, 1H); 6.45 (dd, 1H); 7.62 (t, 1H);

7.89-8.02 (m, 2H); 8.70 (s, 1H); 9.6-11, 0 (b, 1H) ppm.

Example INT16 N- (3-nitro-phenyl) -3-pyrrolidin-1-yl-propionamide

Analogously to Example INT13), from 5.0 g of the compound prepared under Example INT15), 18.2 ml of triethylamine and 2.56 ml of pyrrolidine, after purification by chromatography on silica gel, 5.52 g of the title compound are obtained. 1 H-NMR (DMSO-d6): δ = 1, 60-1, 76 (m, 4H); 2.38-2.58 (m, 6H); 2.72 (t, 2H); 7.60 (t, 1H); 7.85-7.93 (m, 2H); 8.64 (s, 1H); 10.56 (s, 1H) ppm. Example INT17 N- (3-amino-phenyl) -3-pyrrolidin-1-yl-propionamide

5.5 g of the compound described under Example INT16) are dissolved in 200 ml of ethanol and treated with 450 mg of palladium on carbon (10%). It is stirred for 4 hours under a hydrogen atmosphere at room temperature. After filtration through diatomaceous earth and condensing off the solvent on a rotary evaporator, 4.8 g of the title compound are obtained.

1 H-NMR (DMSO-d6): δ = 1.61-1.75 (m, 4H); 2.34-2.53 (m, 6H); 2.68 (t, 2H); 5.02 (s, 2H); 6.21 (d, 1H); 6.55 (d, 1H); 6.82-6.94 (m, 2H); 9.78 (s, 1H) ppm.

Example INT18 3-nitro-N- (3-pyrrolidin-1-yl-propyl) -benzamide

500 mg of 4-nitrobenzoic acid are dissolved in 20 ml of dimethylformamide, mixed with 370 μl of triethylamine, 342 mg of N- (3-aminopropyl) -pyrrolidine and 866 mg of TBTU and stirred for 20 hours at room temperature. The reaction mixture is mixed with semisaturated sodium bicarbonate solution and extracted with dichloromethane. The organic solution is washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and, after purification by chromatography on silica gel, 502 mg of the title compound are obtained. 1 H-NMR (DMSO): δ = 1.84 (m, 6H), 2.63 (m, 4H), 2.78 (m, 2H), 7.61 (m, 1H), 8.22 (dd, 1H), 8.32 (dd, 1H) 8.53 (m, 1H), 9.41 (s, 1H) ppm.

Example INT19 3-amino-N- (3-pyrrolidin-1-yl-propyl) -benzamide 1 g of the compound described under Example INT18) are dissolved in 50 ml of THF and treated with 1 g of Raney nickel. It will be 3 hours under hydrogen atmosphere stirred at room temperature. After filtration through diatomaceous earth and condensing off the solvent on a rotary evaporator, 810 mg of the title compound are obtained. 1 H NMR (DMSO d6): δ = 1.79 (m, 6H), 2.57 (m, 4H), 2.69 (m, 2H), 3.55 (m, 2H), 3.73 (s, 2H), 6.76 (dd, 1 H), 7.02 (m, 1H), 7.17 (m, 2H), 8.52 (s, 1H) ppm.

Example INT20

Pyrrolidine-1-carboxylic acid (4-nitro-phenyl) -amide 1 g of para-nitrophenyl isocyanate are dissolved in 10 ml of acetonitrile and at

Room temperature slowly mixed with pyrrolidine (1.51 ml). It is stirred overnight at room temperature, the solvent is distilled off on a rotary evaporator and the residue is recrystallized from ethanol. This gives 1.1 g of product. 1 H-NMR (DMSO d6): δ = 1.82 (m, 4H), 3.48 (m, 4H), 7.79 (d, 2H), 8.12 (d, 2H), 8.80 (s, 1H) ppm.

Example INT21

Pyrrolidine-1-carboxylic acid (4-amino-phenyl) -amide

1 g of the compound described under example INT20) are dissolved in 50 ml of THF and treated with 1 g of Raney nickel. It is stirred for 3 hours under a hydrogen atmosphere at room temperature. After filtration through diatomaceous earth and condensing off the solvent on a rotary evaporator, 790 mg of the title compound are obtained. 1 H-NMR (DMSO dβ): δ = 1.80 (m, 4H), 3.28 (m, 4H), 4.68 (s, 2H), 6.42 (d, 2H), 7.05 (d, 2H), 7.61 (s, 1H) ppm. Example INT22 N- (3-amino-5-chloro-phenyl) -2,2-dimethyl-propionamide (2056-1)

5.0 g of 5-chloro-1,3-diaminobenzene are dissolved in 50 mL dichloromethane and 5 mL

Dissolved dimethylformamide and treated at 0 ° C with 18.5 mL of diisopropylethylamine and 8.5 mL of pivalic anhydride. It is stirred for one hour at 0 ° C and 5 hours at room temperature. The reaction mixture is treated with half-saturated sodium bicarbonate solution and extracted with a mixture of ethyl acetate and hexane (1: 3). The organic solution is washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and, after purification by chromatography on silica gel, 2.5 g of the title compound are obtained. 1H-NMR (DMSO-d6): (DMSO-d6): δ = 5.37 (s, b, 2H); 6.28 (s, b, 1H); 6.88 (s, b, 1H); 7.48 (s, 1H); 9.00 (s, 1H) ppm.

Example INT23 ethyl (5-nitro-pyridin-2-yl) -amine

395 mg of 2-chloro-5-nitropyridine and 2.5 ml of a 1 M solution of ethylamine in tetrahydrofuran are dissolved in 10 ml of DMSO and stirred at 50 ° C. for 4 hours. The reaction mixture is treated with ethyl acetate and washed three times with half-saturated sodium bicarbonate solution. The organic phase is dried over sodium sulfate. After purification by chromatography on silica gel, 430 mg of the title compound are obtained. 1 H-NMR (DMSO-d6): δ = 1.17 (t, 3H); 3.40 (m, 2H); 6.53 (d, 1H); 8.00-8.23 (m, 2H); 8.91 (d, 1H) ppm. Example INT24 N * 2 * -Ethyl-pyridine-2,5-diamine

420 mg of the compound described under Example INT23) are dissolved in 20 ml of ethanol and mixed with 120 mg of palladium on carbon (10%). It is stirred for 4 hours under a hydrogen atmosphere at room temperature. After filtration through diatomaceous earth and condensing off the solvent on a rotary evaporator, 340 mg of the title compound are obtained.

1 H-NMR (DMSO-d6): δ = 1, 09 (t, 3H); 3.11 (m, 2H); 4.25 (s, 2H); 5.43 (t, 1H); 6.25 (d, 1H); 6.81 (dd, 1H); 7.45 (d, 1H) ppm.

Example INT25 N- (5-nitro-pyridin-2-yl) -acetamide

1.12 g of 2-amino-5-nitro-pyridine, 5.1 mL of triethylamine, and a spatula tip of DMAP are dissolved in 20 mL of tetrahydrofuran. There are added 0.86 ml of acetyl chloride and it is stirred for 24 hours under reflux. The reaction mixture is mixed with ethyl acetate and washed three times with half-saturated sodium bicarbonate solution. The organic phase is dried over sodium sulfate. After purification by chromatography on silica gel and crystallization from ethanol, 340 mg of the title compound are obtained. 1 H-NMR (DMSO-d6): δ = 2.17 (s, 3H); 8.28 (d, 1H); 8.59 (dd, 1H); 9.16 (d, 1H); 11, 25 (8, 1H) ppm. Example INT26 N * 2 * -Ethyl-pyridine-2,5-diamine

340 mg of the compound described under example INT25) are dissolved in 50 ml

Ethanol and 10 ml of dichloromethane and with 120 mg of palladium on carbon (10

%). It is stirred for 4 hours under a hydrogen atmosphere at room temperature. After filtration through diatomaceous earth and condensing off the solvent on a rotary evaporator, 275 mg of the title compound are obtained.

1 H-NMR (DMSO-d6): δ = 2.00 (s, 3H); 5.14 (s, 2H); 6.95 (dd, 1H); 7.66 (d, 1H); 7.73

(d, 1H); 9.99 (s, 1H) ppm.

Example INT27

Bis (5-nitro-pyridin-2-yl) - (2-pyrrolidin-1-yl-ethyl) -amine

i _ 0

395 mg of 2-chloro-5-nitro-pyridine and 2.70 mg of 2-pyrrolidin-1-yl-ethylamine are dissolved in 5 ml of DMSO and stirred at 100 ° C for 6 hours. The reaction mixture is treated with dichloromethane and washed three times with half-saturated sodium bicarbonate solution. The organic phase is dried over sodium sulfate. After purification by chromatography on silica gel, 51 mg of the title compound are obtained. 1 H-NMR (DMSO-d6): δ = 1.59 (m, 4H); 2.43 (m, 4H); 2.75 (t, 2H); 4.42 (t, 2H); 7.56 (d, 2H); 8.48 (dd, 2H); 9.19 (d, 2H) ppm. Example INT28 bis (5-amino-pyridin-2-yl) - (2-pyrrolidin-1-yl-ethyl) -amine

50 mg of the compound described under example INT27) are dissolved in 10 ml of ethanol and treated with 20 mg of palladium on carbon (10%). It is stirred for 4 hours under a hydrogen atmosphere at room temperature. After filtration through diatomaceous earth and condensing off the solvent on a rotary evaporator, 41 mg of the title compound are obtained. 1 H-NMR (DMSO-d6): δ = 1.97 (m, 4H); 3.00-3.47 (mb, 6H); 4.20 (t, 2H); 5.03 (s, 4H); 6.76 (d, 2H); 7.00 (dd, 2H); 7.77 (d, 2H) ppm.

Example INT29

rac-1,1,1-trifluoro-2- [4'-nitro-phenyl] propane-2-ol

Dissolve 0.7 g of 4-nitroacetophenone in 9 mL of THF and add 3.2 mL of (trifluoromethyl) trimethylsilane and 9 mg of tetra-n-butylammonium fluoride trihydrate. The solution is stirred for 5 hours at room temperature. For working up, add 16 mL dilute hydrochloric acid (9 + 1). After addition of 200 ml of water, it is extracted with ethyl acetate. The organic phase is washed with concentrated sodium bicarbonate solution and water, dried over magnesium sulfate and concentrated. The resulting oil is taken up in 40 ml of acetone, combined with 6.1 ml of hydrochloric acid and stirred for 2 hours at room temperature. It is mixed with sodium bicarbonate solution and extracted with ethyl acetate. The product obtained after drying over magnesium sulfate and evaporation of the solvent is purified on silica gel. He will receive 0.82 g of the title compound as nearly colorless crystals. 1 H-NMR (DMSO-d6): δ = 1.74 (s, 3H); 6.99 (s, 1H); 7.88 (d, 2H); 8.26 (d, 2H) ppm. Example INT30

4'-nitro-N-methyacetanilid 2.5 g of N- (4-nitro-phenyl) -acetamide are dissolved in 50 ml of warm acetone and treated with 3 g of potassium hydroxide and 3 g of methyl iodide. It is heated for 10 min at reflux. The residue remaining after evaporation of the acetone is taken up in water. It is extracted with ethyl acetate. The organic phase is washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated. 2.4 g of the title compound are obtained as yellow crystals.

1 H-NMR (CDCl 3): δ = 2.02 (s, 3H); 3.34 (s, 3H); 7.39 (d, 2H); 8.28 (d, 2H) ppm.

Intermediate INT31 N- (2-dimethylamino-ethyl) -3-nitro-benzenesulfonamide

A solution of 3-nitro-benzenesulfonyl chlorides (1 equivalent) in acetonitrile is added dropwise at 0 ° C to a solution of N * 1 *, N * 1 * -dimethyl-ethane-1,2-diamine (2.2 equivalents) in acetonitrile and stirred overnight at room temperature. The reaction is terminated by adding sodium hydroxide (1 N) and extracted three times with 2-methoxy-2-methyl-propane. The combined organic phases are freed from the solvent on a rotary evaporator and purified by column chromatography. The title compound is obtained in 43% yield. 1 H-NMR (CDCl3, 300 MHz), (selected peaks) δ = 2.11 (s, 6H); 2.39 (m, 2H); 3.03 (m, 2H); 7.75 (t, 1H); 8.21 (dd, 1H); 8.42 (dd, 1H); 8.72 (m, 1H). Intermediate INT32 Dimethyl- [2- (4-nitro-phenoxy) -ethyl] -amine

A suspension of 10 g of 4-nitrophenol, 11 g of (2-chloro-ethyl) -dimethyl-amine and 27.1 g of potassium carbonate in 200 ml of acetone is refluxed for 15 hours. The batch is freed from the solvent under reduced pressure and the residue is taken up in ethyl acetate. It is extracted three times with 200 ml of sodium hydroxide solution (1N) and the combined organic phases are dried over sodium carbonate, the solvent is distilled off on a rotary evaporator and the title compound is obtained in 50% yield.

1 H NMR (CDCl 3, 300 MHz), (selected peaks) δ = 2.35 (s, 6H); 2.78 (m, 2H); 4.16 (m, 2H); 6.97 (d, 2H); 8.19 (d, 2H).

Intermediate INT33

4- (2-dimethylamino-ethoxy) -phenylamine 14.9 g of the compound prepared under Example INT LW32) are dissolved in 300 ml of methanol and treated with 2 g of palladium on carbon (10%) and it is stirred under a hydrogen atmosphere at room temperature. After completion of the hydrogen uptake, the catalyst is filtered off and the crude product is freed from the solvent on a rotary evaporator. The title compound is obtained in quantitative yield. The crude product is used without further purification in the next stage. 1 H NMR (CDCl 3, 300 MHz), (selected peaks) δ = 2.35 (s, 6H); 2.70 (m, 2H); 4.00 (m, 2H); 6.63 (d, 2H); 6.79 (d, 2H). The following intermediates are prepared analogously to the methods described above.

The following intermediates are already disclosed in patent application PCT / EP03 / 04450 and are not claimed in the present application.

4.25 ml of ethyl isothiocyanate are added at 25 ° C. to a mixture of 5 g of ethyl cyanoacetate and 5 ml of triethylamine. Then allowed to stir for 6 hours at 50 ° C. Thereafter, the reaction mixture is concentrated in vacuo. The residue is taken up in ethanol and poured onto 150 ml of ice-cold 1 normal hydrochloric acid. The mixture is stirred for 3 hours at 25 ° C and then filtered from the residue. The resulting solid is washed with water. There are obtained 7 g of product. Molecular weight = 200,261; MS (ESI): [M + 1] + = 201. Example INT123)

(E or Z) -cyano- (3-ethyl-4-oxo-thiazolidin-2-ylidene) -acetic acid ethyl ester 7.82 g of the compound described under example INT122) are dissolved in 100 ml of tetrahydrofuran. It slowly adds a solution of 3.9 ml of bromoacetyl chloride and allowed to stir for 8 hours at 25 ° C. Then the reaction mixture is poured onto saturated aqueous sodium bicarbonate solution. The mixture is stirred for 1 hour and then extracted with ethyl acetate. The organic phase is washed with saturated Natriumchloridlödung, dried over sodium sulfate and concentrated in vacuo. The resulting crude product is recrystallized from a mixture of ethyl acetate / diisopropyl ester. There are obtained 7.7 g of product. ¹ H-NMR (CDCl ₃ ): δ = 1.36 (6H); 3.70 (2H); 4.32 (4H) ppm.

Example INT124) (E or Z) -cyano- (5- (E / Z) -ethoxymethylene-3-ethyl-4-oxo-thiazolidin-2-ylidene) - oleic acid ethyl ester

A mixture of 1.54 g of the substance described under example INT123), 2.5 ml of triethyl orthoformate and 3.5 ml of acetic anhydride are refluxed for 8 hours. Subsequently, the reaction mixture is poured onto ice-water. The mixture is stirred for 3 hours and then filtered from the residue. The resulting solid is washed with water. This gives 1.28 g of product. ¹ H-NMR (CDCl ₃ ): δ = 1.38 (9H); 4.20-4.40 (6H); 7.72 (1H) ppm. Example INT125)

(E or Z) -cyano (3-ethyl-4-oxo-thiazolidin-2-ylidene) -acetic acid allyl ester

To a suspension of 12.8 g of sodium hydride (60%) in 200 ml of dimethylformamide is added at 0 ° C, a solution of 37.6 mL Cyanessigsäuereallylester in 60 ml of dimethylformamide. The mixture is stirred for 10 minutes at 0 ° C and then added a solution of 28.0 mL of ethyl isothiocyanate in 60 ml of dimethylformamide. The mixture is then stirred for 2 hours at 25 ° C. Then a solution of 32 mL bromoacetyl chloride in 60 mL dimethylformamide is added at 0 ° C and stirred for 15 hours at 25 ° C after. Then the reaction mixture is poured onto saturated sodium bicarbonate solution. It is extracted with ethyl acetate, the organic phase is washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The crude product is purified by column chromatography on silica gel with a mixture of hexane / ethyl acetate. 33.9 g of product are obtained.

1 H-NMR (CDCl ₃ ): D = 1.23 (3H); 4,11 (2H); 4.71 (2H); 5.25 (1H); 5.37 (1H); 5.90-6.04 (1H) ppm.

Example INT126) (E or Z) -cyano- (5- (E / Z) -ethoxymethylene-3-ethyl-4-oxo-thiazolidin-2-ylidene) - allyl acetate

Analogously to Example INT124), 12.8 g of the compound described under example INT125), 20.9 ml of triethyl orthoformate and 29.4 ml of acetic anhydride give 14.8 g of product.

1 H-NMR (CDCl ₃ ): D = 1, 32-1, 45 (6H); 4.23 (2H); 4.38 (2H); 4.73 (2H); 5.29 (1H); 5.41 (1H), 5.92-6.05 (1H); 7.72 (1H) ppm.

To a suspension of 0.4 g of sodium hydride (60%) in 5 ml of dimethylformamide is added at 0 ° C, a solution of 1.75 g Cyanessigsäuerebenzylester in 10 ml of dimethylformamide. The mixture is stirred for 10 minutes at 0 ° C and then added a solution of 876 ul ethyl isothiocyanate in 5 ml of dimethylformamide. The mixture is then stirred for 2 hours at 25 ° C. Then added at 0 ° C, a solution of 1 ml of bromoacetyl chloride in 5 ml of dimethylformamide and stirred for 15 hours at 25 ° C after. Subsequently, the reaction mixture is saturated

Sodium bicarbonate solution poured. It is extracted with dichloromethane, the organic phase is washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The crude product is purified by column chromatography on silica gel with a mixture of hexane / ethyl acetate. This gives 1.1 g of product.

1 H-NMR (CDCl ₃ ): G = 1.35 (3H); 3.70 (2H); 4.30 (2H); 5.31 (2H), 7.30-7.48 (5H) ppm.

Example INT128)

(E or Z) -cyano- (5- (E / Z) -ethoxymethylene-3-ethyl-4-oxo-thiazolidin-2-ylidene) -benzyl acetate

Analogously to example INT124), from 11 g of the compound described under example INT127), 1.49 ml of triethylorthoformate and 2.1 ml of acetic anhydride 1, 26 g of product are obtained.

1 H-NMR (CDCl ₃ ): □ = 1, 30-1, 45 (6H); 4.25 (2H); 4.38 (2H); 5.29 (2H); 7.30-7.48 (5H), 7.72 (1H) ppm. Example INT129)

[3-Butyl-4-oxo-thiazolidine (2- (E or Z)) -idene] -cyano-acetic acid ethyl ester

Analogously to the method described above, the product can be obtained. 1 H-NMR (DMSO-d6): δ = 0.90 (t, 3H); 1.25 (t, 3H); 1, 32 (m, 2H); 1, 59 (m, 2H); 3.97 (s, 2H); 4.15 (t, 2H); 4.22 (q, 2H) ppm.

Example INT130) [3-butyl-5- [1-ethoxy-meth (E / Z) -ylidene] -4-oxo-thiazolidine (2- (E or Z)) -idene] -cyano-acetic acid ethyl ester

Analogously to Example INT124), the product of Example INT 29) can be obtained. 1 H NMR (DMSO-d6): δ = 0.90 (t, 3H); 1.20-1, 40 (m, 8H); 1, 61 (m, 2H); 4.15 (t, 2H); 4.23 (q, 2H); 4.39 (q, 2H) ppm.

Example INT131 (E or Z) -Cyano- (3-ethyl-4-oxo-5- (E / Z) - {[4- (2-pyrrolidin-1-yl-ethyl) -phenylamino] -methylene} -thiazolidine -2-ylidenes) -acetic acid ethyl ester

3.43 g of the compound described under example INT4) are dissolved in 60 ml of ethanol. 4.11 g of the compound described under example INT124) are added and the mixture is stirred at reflux for 15 hours. After cooling, the reaction mixture is filtered and the solid recrystallized from ethanol. 4.95 g of the title compound are obtained as a pH-dependent 5- (E / Z) -isomer mixture. 1 H NMR (DMSO-d6, stored over K2CO3, major isomer): δ = 1.16-1.33 (m, 6H); 1, 59-1, 75 (m, 4H); 2.38-2.50 (m, 4H); 2.59 (t, 2H); 2.69 (t, 2H); 4.13-4.31 (m, 4H); 7.10-7.29 (m, 4H); 8.19 (s, 1H); 10.53 (s, 1H) ppm.

Example INT132

(E or Z) -cyano- (3-ethyl-4-oxo-5- (E / Z) - {[3- (3-pyrrolidin-1-yl-propionylamino) -phenyl-amino] -methylene} -thiazolidine-2 -ylidene) -acetic acid ethyl ester

3.0 g of the compound described under example INT17) are dissolved in 50 ml of ethanol. 3.82 g of the compound described under example INT124) are added and the mixture is stirred at reflux for 4 hours. The solvent is condensed on a rotary evaporator. After purification by chromatography on silica gel, 5.3 g of the title compound are obtained as a pH-dependent 5- (E / Z) isomer mixture.

1 H NMR (DMSO-d6, stored over K 2 CO 3, major isomer): δ = 1.18-1.34 (m, 6H); 1, 62-1, 78 (m, 4H); 2.48-2.62 (m, 6H); 2.78 (t, 2H); 4.16-4.32 (m, 4H); 6.99 (d, 1H); 7.18 (d, 1H); 7.29 (t, 1H); 7.75 (s, 1H); 8.10 (s, 1H); 10.19 (s, 1H); 10.60 (s, 1H) ppm.

The following compounds were prepared analogously to the methods described above.

The following examples describe the preparation of compounds according to the invention, without limiting these to these examples. These compounds can also be used as intermediates for the preparation of substances of the general formula (I) according to the invention. Here, the esters are cleaved into the free acids. It has been noticed that the compounds which have an allyl ester are more easily split into the free acid than ethyl esters.

Example 1 (E or Z) -Cyano- (3-ethyl-5- (E / Z) - {[4- (2-morpholin-4-yl-ethanesulfonylamino) -O-phenylamino] -methylene} -4-oxo thiazolidin-2-ylidenes) -acetic acid ethyl ester

58 mg of the compound described under example INT10) are dissolved in 2 mL dichloromethane, combined with 5 mL trifluoroacetic acid and stirred for 30 minutes at room temperature. The reaction mixture is concentrated on a rotary evaporator 5. The residue is dissolved in 3 ml of ethanol. 0.7 ml of triethylamine and 36 mg of the compound described under example INT124) are added and the mixture is stirred at reflux for 3 hours. The solvent is condensed on a rotary evaporator. After purification by chromatography on silica gel, 55 mg of the title compound are obtained as a pH-dependent 5- (E / Z) O mixture of isomers. 1 H NMR (DMSO-d6, stored over K2CO3, major isomer): δ = 1, 15-1, 31 (m, 6H); 2.30 (m, 4H); 2.66 (t, 2H); 3.22 (t, 2H); 3.50 (m, 4H); 4.14-4.31 (m, 4H); 7.19 (d, 2H); 7.29 (d, 2H); 8.18 (s, 1H); 9.50-10.75 (b, 2H) ppm. 5 Example 2

(E or Z) -cyano- [3-ethyl-4-oxo-5- (E / Z) - ({4 - [(pyrrolidine-1-carbonyl) -amino] -phenylamino} -methylene) -thiazolidine-2 -ylidene] -acetic acid ethyl ester

205 mg of the compound described under example INT21) are dissolved in 10 ml of ethanol. 100 mg of the compound described under example INT124) are added and the mixture is stirred at reflux for 15 hours. After cooling, the reaction mixture is filtered and the solid recrystallized from ethanol. This gives 118 mg of the title compound as a pH-dependent 5- (E / Z) -isomerengemisch. 1 H-NMR (DMSO-d6, stored over K2CO3, major isomer): δ = 1.21 (m, 6H), 1.81 (m, 4H), 3.32 (m, 4H), 4.20 (m, 2H), 7.18 (d, 2H), 7.50 (d, 2H), 8.12 (s, 1H) ppm.

Example 3 (E or Z) -Cyano- (3-ethyl-5- (E / Z- ({4- [3- (4-methyl-piperazin-1-yl) -propionylamino] -phenylamino} -methylene} - 4-oxo-thiazolidin-2-ylidene) - allyl acetate

1 g of the compound described under example INT126) and 0.93 g of the compound described under example INT14) are stirred in 20 ml of ethanol at 100 ° C. for 15 h. The reaction mixture is on a rotary evaporator for

Dry concentrated. The crude product thus obtained is

Chromatography on silica gel. There are obtained 1.6 g of the title compound as a pH-dependent 5- (E / Z) ~ isomer mixture. 1 H-NMR (DMSO-d6, major isomer): δ = 1.25 (3H); 2,12 (3H); 2.21-2.55 (10H)

2.60 (2H); 4.23 (2H); 4.70 (2H); 5.25 (1H); 5.88 (1H); 5.90-6.06 (1H); 7.27

(2H); 7.55 (2H); 8.16 (1H); ppm. Example 4

(E or Z) -cyano- (3-ethyl-5- (E / Z- ({4- [3- (4-methylpiperazin-1-yl) -propionylamino] -phenylamino} -methylene} -4- oxo-thiazolidin-2-ylidene) - benzyl acetate

In analogy to Example 3), 7.4 g of the title compound are obtained by reacting 5 g of the compound described in Example INT128) and 4 g of the compound described in Example INT14) in 100 ml of ethanol.

1 H-NMR (DMSO-d6, major isomer): δ = 1.23 (3H); 2.16 (3H); 2.22-2.57 (10H) 2.61 (2H); 4.23 (2H); 5.28 (2H); 7.26 (2H); 7.31-7.48 (5H); 7.58 (2H); 8.16 (1H); ppm.

Example 5 (E or Z) -Cyano- (3-ethyl-5- (E / Z) - {[4- (2-pyrrolidin-1-yl-ethylcarbamoyl) -phenylamino] -methylene} -4-oxo-thiazolidine -2-ylidene) -essigsäureallylester

12.2 g of the compound described under Example 50), 5.5 ml of triethylamine and 12.8 g of TBTU are introduced into 150 ml of DMF and stirred for 30 minutes at room temperature. 4.5 g of N- (2-aminoethyl) -pyrrolidine are added and it is stirred overnight at room temperature. The reaction mixture is treated with sodium chloride solution and extracted with a dichloromethane / methanol mixture. After purification by chromatography on silica gel, 13.2 g of the title compound are obtained as a pH-dependent 5- (E / Z) -isomer mixture. 1 H-NMR (DMSO-d6, major isomer): δ = 1, 23 (3H); 1.75-2.33 (4H); 2.90-3.13 (4H); 3.52 (2H); 4.23 (2H); 4.72 (2H); 5.26 (1H), 5.89 (1H); 5.91-6.07 (1H); 7.40 (2H); 7.90 (2H); 8.25 (1H); 8.69 (1H); ppm. The following compounds are prepared analogously to the methods described above.

Example 141 [5- [1- [acetyl- (6-amino-pyridin-3-yl) -amino] -meth- (E / Z) -lyidene] -3-ethyl-4-oxo-thiazolidine (2) (E or Z)) - ylidenes] -cyano-acetic acid ethyl ester

420 mg of the compound described in Example 82) and 0.13 ml of triethylamine are dissolved in 5 ml of dichloromethane. 0.02 ml of acetic anhydride are added and the mixture is stirred for 2 hours at room temperature. The reaction mixture is treated with dichloromethane and washed three times with half-saturated sodium bicarbonate solution. The organic phase is dried over sodium sulfate. After purification by chromatography on silica gel, 340 mg of the title compound are obtained.

(DMSO-d6, stored over K2CO3, major isomer): δ = 1.12-1, 28 (t, 3H); 2.01 (s, 3H); 4.09-4.27 (m, 4H); 6.51-6.64 (m, 3H); 7.46 (dd, 1H); 7.98 (d, 1H); 8.55 (s, 1H) ppm.

The following examples describe the preparation of compounds according to the invention, without limiting these to these examples. These compounds can also be used as intermediates for the preparation of substances of the general formula (I) according to the invention.

Example 142

(E or Z) -Cyano- (3-ethyl-4-oxo-5- (E / Z) - {[4- (2-pyrrolidin-1-yl-ethyl) -phenylamino] -methylene} thiazolidine-2 -ylidene) -acetic acid

2.05 g of potassium tert-butylate are initially introduced into 50 ml of tetrahydrofuran at 0 ° C. and admixed with 76.4 μl of water. 1.0 g of the compound described under example INT131) are added and the mixture is stirred at 0 ° C. for 30 minutes and at room temperature for 20 hours. At 0 ° C., 8.25 ml of two molar hydrochloric acid in diethyl ether are added and the mixture is stirred for one hour at room temperature. The solvent is condensed off in a high vacuum, and the residue is reacted further without further purification. Molar wet = 412,514; MS (ESI): [M + 1] + = 413.

Example 143

(E or Z) -cyano- (3-ethyl-5- (E / Z- ({4- [3- (4-methylpiperazin-1-yl) propylamino] phenylamino} methylene} -4- oxo-thiazolidin-2-ylidene) - acetic acid

4.4 g of the compound described in Example 3), 0.91 g of Pd (PPh ₃ ) ₄ and 6.9 ml of morpholine are stirred in 150 ml of tetrahydrofuran for 15 min. After addition of 45 ml of triethylamine, the reaction mixture obtained is taken to dryness on a rotary evaporator. The crude product thus obtained is obtained by chromatography with a dichloromethane / methanol mixture Cleaned silica gel. 3.5 g of the title compound are obtained as a pH-dependent 5- (E / Z) -isomer mixture. 1 H-NMR (DMSO-d6, major isomer): δ = 1.20 (3H); 2.19 (3H); 2.23-2.55 (10H) 2.61 (2H); 4.20 (2H); 7.18 (2H); 7.52 (2H); 7.87 (1H); ppm.

The following compounds are prepared analogously to the methods described above.

124

The following examples describe the preparation of the compounds of the general formula (I) according to the invention, without restricting these to these examples.

Example 166

2- (E or Z) -cyano-N-ethyl-2- (3-ethyl-4-oxo-5- (E / Z) - {[4- (2-pyrrolidin-1-yl-ethyl) -phenylamino ] -methylene} -thiazolidin-2-ylidene) -acetamide

0.2 mmol) are dissolved in 10 ml of dimethylformamide, treated with 139 ul of triethylamine, 150 ul of a 2M solution of ethylamine in tetrahydrofuran and 96 mg of TBTU and stirred for 20 hours at room temperature. The reaction mixture is mixed with half-saturated sodium bicarbonate solution and extracted with dichloromethane. The organic solution is washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and, after purification by chromatography on silica gel, 51 mg of the title compound are obtained as a pH-dependent 5- (E / Z) isomer mixture. 1 H-NMR (DMSO-d6, stored over K2CO3, major isomer): δ = 1, 07 (t, 3H); 1, 23 (t, 3H); 1.65 (m, 4H); 2.45 (m, 4H); 2.54-2.62 (m, 2H); 2.62-2.75 (m, 2H); 3.20 (pentuplet, 2H); 4.21 (q, 2H); 7.20 (s, 4H); 7.67 (t, 1H); 8.04 (s, 1H); 10.23 (s, 1H) ppm.

Example 167

2- (E or Z) - {5- (E / Z) - [(3-Amino-phenylamino) -methylene] -3-ethyl-4-oxo-thiazolidin-2-ylidene} -2-cyano-N- ethyl-acetamides

100 mg of the compound described in Example 215) are dissolved in 20 ml of ethanol, combined with 291 mg of tin-1-chloro dihydrate and stirred under reflux for 4 hours. Another 145 mg tin-II-chloride dihydrate are added and another 2

Stirred under reflux for hours. The reaction mixture becomes more saturated Sodium bicarbonate solution, stirred for 30 minutes at room temperature and extracted with a mixture of chloroform, dichloromethane and methanol (5: 5: 1). The organic solution is dried over sodium sulfate, concentrated and, after purification by chromatography on amino-phase silica gel, 50 mg of the title compound are obtained as a pH-dependent 5- (E / Z) -isomer mixture. 1 H-NMR (DMSO-d6, stored over K 2 CO 3, major isomer): δ = 1, 07 (t, 3H); 1, 26 (t, 3H); 3.21 (q, 2H); 4.22 (q, 2H); 5.23 (s, 2H); 6.29 (d, 1H); 6.39 (d, 1H); 6.45 (s, 1H); 6.97 (t, 1H); 7.68 (t, 1H); 7.95 (d, 1H); 10.18 (d, 1H) ppm.

Example 168

2- (E or Z) -cyano-N-ethyl-2- [3-ethyl-5- (E / Z) - ({3- [2- (2-methoxy-ethoxy) -acetylamino] -phenylamino} - methylene) -4-oxo-thiazolidin-2-ylidene] -acetamide

16.5 μL 2- (2-methoxyethoxy) -acetic acid are placed in 1 mL tetrahydrofuran at 0 ° C and treated with 37 μL triethylamine and 18.5 μL isobutyl chloroformate. It is stirred for 30 minutes at 0 ° C, 50 mg of the compound described in Example 167), dissolved in 2 mL of tetrahydrofuran are added and it is stirred for a further 2 hours at room temperature. The reaction mixture is mixed with half-saturated sodium bicarbonate solution and extracted with dichloromethane. The organic solution is washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and, after purification by chromatography on silica gel, 35 mg of the title compound are obtained as a pH-dependent 5- (E / Z) -isomer mixture. 1 H NMR (DMSO-d6, stored over K 2 CO 3, major isomer): δ = 1, 08 (t, 3H); 1.25 (t, 3H); 3.12-3.25 (m, 2H); 3.30 (s, 3H); 3.54 (t, 2H); 3.68 (t, 2H); 4.09 (s, 2H); 4.22 (q, 2H); 6.97 (s, 1H); 7.20-7.30 (m, 2H); 7.55-7.77 (m, 2H); 8.04 (s, 1H); 9.68 (s, 1H); 10.39 (s, 1H) ppm. The following compounds are prepared analogously to the methods described above.

DDDDDDDDD DDDDDDDDD

Analogous to the synthesis of Example 166, the following compounds can also be prepared:

example 1

The following examples describe the biological activity of the compounds according to the invention:

PLK enzyme assay

Recombinant human Plk-1 (6xHis) was purified from baculovirus-infected insect cells (Hi5).

10 ng (recombinantly prepared, purified) PLK enzyme is incubated for 90 min at room temperature with biotinylated casein and 33P-D-ATP as substrate in a volume of 15 .mu.l in 384well Greiner Small Volume microtiter plates (final concentrations in the buffer: 660 ng / ml PLK 0.7 μM casein, 0.5 μM ATP including 400 nCi / ml 33P-γ-ATP, 10 mM MgCl 2, 1 mM MnCI 2, 0.01% NP40, 1 mM DTT, protease inhibitors, 0.1 mM Na 2 VO 3 in 50 mM HEPES pH 7.5). To terminate the reaction, 5 μl of stop solution (500 μM ATP, 500 mM EDTA, 1% Triton X100, 100 mg / ml streptavidin coated SPA beads in PBS) is added. After sealing the microtiter plate by foil, the

Beads sedimented by centrifugation (10 min, 1500 rpm). Incorporation of 33P-γ-ATP into casein is determined as a measure of enzyme activity by β-counting. The measure of the inhibitor activity is referenced against a solvent control (= uninhibited enzyme activity = 0% inhibition) and the mean of several batches containing 300 μM wortmannin (= fully inhibited enzyme activity = 100% inhibition).

Test substances are used in various concentrations (0 μM and in the range 0.01-30 μM). The final concentration of the dimethylsulfoxide solvent is 1.5% in all batches. proliferation assay

Cultured human MaTu breast tumor cells were plated at a density of 5000 cells / measuring point in a 96-well multititer plate in 200 μl of the appropriate growth medium. After 24 hours, the cells of one plate (zero point plate) were stained with crystal violet (see below), while the medium of the other plates was replaced by fresh culture medium (200 μl) containing the test substances at various concentrations (0 μM and in the range 0.01 - 30 μM, the final concentration of the solvent dimethylsulfoxide was 0.5%) were added replaced. The cells were in for 4 days

Presence of the test substances incubated. Cell proliferation was determined by staining the cells with crystal violet. The cells were fixed by adding 20 μl / measuring point of an 11% glutaraldehyde solution for 15 minutes at room temperature. After washing the fixed cells three times with water, the plates were dried at room temperature. The cells were stained by the addition of 100 μl / measuring point of a 0.1% crystal violet solution (pH adjusted to pH 3 by the addition of acetic acid). After washing the stained cells three times with water, the plates were dried at room temperature. The dye was dissolved by adding 100 μl / measuring point of a 10% acetic acid solution. The extinction was determined photometrically at a wavelength of 595 nm. The percentage change in cell growth was calculated by normalizing the measurements to the absorbance values of the zero plate (= 0%) and the absorbance of the untreated (0 μM) cells (= 100%).

The results of the PLK enzyme assay are listed in Table 1 below: TABLE 1

The results of other PLK enzyme assays and the proliferation assay are listed in Tables 2 and 3 below: TABLE 2 Amides

Table 3: Esters

Tables 1 to 3 show that the compounds according to the invention inhibit PLK in the nanomolar range.

Description of the figure

Fig. 1 shows the function of Pik -1

In this mean:

1. Entry into mitosis: Pik-1 activates CDC25 C. This activates the CDK / cyclin B complex and transfers the cell from G2 to M-status.

2. Onset of Mitosis: PIkl plays an important role during cytokinesis, especially in the formation of bipolar spindle apparatus and chromosome separation during the late mitosis phase. Plk-1 is also needed during centrosome maturation and binds to so-called 'kinesin engines'.

3. Termination of Mitosis: Plk-1 activates the APC / C complex (anaphase promoting cormplex / cyclosome; Kotani et al., 1998;). APC / C as E3 enzyme catalyzes the polyubiquitination of specific substrates, e.g. Cyclin B. Such Ubϊquitinilierung of proteins ultimately leads to their degradation in the proteasome. This in turn leads to a reduction of cell cycle regulators below a critical value and to the exit from the mitosis phase into the so-called G1 status of the cell (M-G1 transition).

Claims

claims

1 . Compounds of the general formula I

(I) in which Q is aryl or heteroaryl, A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted, identical or different, with halogen, hydroxy, C ₃ -C ₆ Heterocycloalkyl or -CC ³ R ⁴ or -CO (NR ³ ) -M -substituted C ₁ -C ₃ -alkyl or C ₁ -C ₆ -alkoxy, where the heterocycloalkyl itself is optionally substituted by one or more nitrogen, oxygen and / or or sulfur atoms may be interrupted and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally mono- or polysubstituted, identically or differently, with C ₁ -C ₃ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₁ -C -hydroxyalkyl or with the group --NR ⁴ , or -NR ³ (CO) -L , -NR ³ (CO) -NR ³ -L, -COR ⁶ , -CO (NR ³ ) -M, - NR ³ (CS) NR ³ R ⁴ , -NR ³ SO ₂ -M, -SO ₂ -NR ³ R ⁴ or -SO ₂ (NR ³ ) -M, L is optionally mono- or polysubstituted, identically or differently _Cι-C6 hydroxyalkoxy, Cι-C ₆ alkoxyalkoxy, C ₃ -C ₆ - heterocycloalkyl or with the group -NR ³ R ^4, substituted d- C ₆ alkyl, or heteroaryl, wherein the heterocycloalkyl itself optionally substituted by one or more Nitrogen, oxygen and / or sulfur atoms may be interrupted and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and itself optionally mono- / or the ring or polysubstituted, identically or differently, with Cι-C ₆ alkyl, C ₃ -C ₆ cycloalkyl, CrC _θ hydroxyalkyl or with the group - NR ³ R ⁴ may be substituted,

M ₆ alkyl optionally mono- or polysubstituted, identically or differently, with the group -NR ³ R ⁴ or C ₃ -C ₆ heterocycloalkyl substituted CrC, X is -NH- or -NR ⁵ -, R ¹ is optionally mono- or polysubstituted by identical or different substituents with halogen-substituted dC ₄ -AlkyI, C ₃ -cycloalkyl, allyl or propargyl, R ^{2 is} hydrogen or optionally mono- or polysubstituted by identical or different substituents with halogen, hydroxy, cyano, -C _C6 alkyl, CRCE-alkoxy, Cι-C ₆ hydroxyalkyl, C ₃ -C ₆ - cycloalkyl, C ₃ -C ₆ heterocycloalkyl, Cι-C ₆ alkynyl, aryl, aryloxy, heteroaryl or with the group - S-C ₁ -C ₆ -alkyl, -COR ⁶ , -NR ³ R ⁴ , -NR ³ (CO) -L or -NR ³ COOR ⁷ substituted -CC ₆ alkyl, Ci-Cβ-alkoxy, C -Cs Alkenyl, C ₁ -C ₆ alkynyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ - heterocycloalkyl, aryl or heteroaryl, wherein the heterocycloalkyl itself is optionally interrupted by one or more nitrogen, oxygen and / or sulfur atoms his may and / or optionally by one or more - (CO) - or -SO ₂ - groups in the ring may be interrupted and / or optionally one or more double bonds may be contained in the ring and wherein aryl, heteroaryl, C ₃ -C ₆ -cycloalkyl and / or the C ₃ - C ₆ -Heterocycloalkylring each themselves optionally one or more times, the same or differently, with cyano, halogen, hydroxy, C -Cβ alkyl, Cι-C ₆ hydroxyalkyl, optionally substituted one or more times, identically or differently with halogen substituted Cι-C ₆ -alkoxy, C ₃ -C ₆ cycloalkyl, C ₃ -C 4 heterocycloalkyl, aryl, benzyl or heteroaryl, or represents the group -NR ³ R ⁴ , -NR ³ (CO) -L, -NR ³ (CS) NR ³ R ⁴ , or R ² and R ⁵ together form a C ₃ -C ₆ heterocycloalkyl ring which is interrupted at least once by nitrogen and may optionally be interrupted one or more times by oxygen or sulfur and / or optionally by one or more - (CO) - or -SO ₂ - Groups in the ring may be interrupted and / or optionally one or more dop pelbindungen can be contained in the ring and / or the ring itself optionally one or more times, same or different with cyano, halogen, hydroxy, -CC ₆ - alkyl, C ₃ -C ₆ -cycloalkyl, Ci-Ce-hydroxyalkyl, d Ce-alkoxyalkyl or with the group -NR ³ R ⁴ or -COR ⁶ may be substituted and / or with optionally mono- or polysubstituted, identically or differently with halogen, -CC ₆ -alkoxy or with the group - COR ⁶ substituted Aryl or heteroaryl may be substituted,

R and R ⁴ are independently hydrogen or one is optionally substituted one or more times, identically or differently with halogen, hydroxy, C ₃ -C ₆ heterocycloalkyl, CrC ₆ - hydroxyalkoxy or substituted with the group -NR ³ R ⁴ Ci- Ce -Alkyl, C -C ₆ alkoxy, -CO-CrCe-AIkyl or aryl, wherein the heterocycloalkyl itself is optionally substituted by one or more nitrogen, oxygen and / or sulfur atoms may be interrupted and / or may optionally be interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C ₆ -Heterocycloalkylring itself in each case optionally mono- or polysubstituted, identically or differently, with cyano, halogen, Cι-C ₆ -alkyl, C ₆ hydroxyalkyl, CC ₆ - alkoxy, C ₃ -C ₆ cycloalkyl, or with the group -NR ³ R ⁴ or - CO-NR ³ R ⁴ may be substituted, or

R ³ and R ⁴ together form a C ₃ -C ₆ -heterocycloalkyl ring which is interrupted at least once by nitrogen and may optionally be interrupted by one or more times by oxygen or sulfur and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the heterocycloalkyl itself itself optionally one or more times, same or different with Ci-Cβ-alkyl, C ₃ -C 6- cycloalkyl, Cι-C ₆ hydroxyalkyl, Cι-C ₆ alkoxyalkyl, cyano, hydroxy, or may be substituted with the group -NR ³ R ^4, R ⁵ singly or multiply optionally, the same or differently with halogen, hydroxy, cyano , C ₁ -C ₆ -alkoxy, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -heterocycloalkyl, or d-Ce-alkyl substituted by -NR ³ R ⁴ , C ₁ -C ₆ -alkenyl, C -C ₆ alkynyl, wherein the heterocycloalkyl itself may optionally be replaced by one or more St ickstoff, oxygen and / or sulfur atoms may be interrupted and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C itself in each case optionally mono- ₆ -heterocycloalkyl or more times, identically or differently, with cyano, halogen, Ci-Ce-alkyl, Cι-C ₆ hydroxyalkyl, C ₆ -C - AJkoxy, C ₃ -C ₆ -cycloalkyl, or may be substituted by the group -NR ³ R ⁴ or - CO-NR ³ R ⁴ ,

R ^{6 is} hydroxy, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy or the group -NR ³ R ⁴ , R ^{7 is} - (CH ₂ ) _n -aryl or - (CH ₂ ) _n -heteroaryl and n is 1 to 6, and their stereoisomers, diastereomers, enantiomers and salts, with the proviso that the following compounds are not included in the general formula

(I): {2-Cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -ylidene] -acetylamino} -acetic acid methyl ester,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- pyridin-3-ylmethyl-acetamide,

2-Cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) - y! Idenes] - N- (3-imidazol-1-yl-propyl) -acetamide,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- (4-fluoro-benzyl) -acetamide,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- (3-morpholin-4-yl-propyl) acetamides, 2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] thiazolidine ( 2- (E or Z)) - ylidenes] - N - (2-morpholin-4-yl-ethyl) -acetamides,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- [3- (2-oxo-pyrrolidin-1-yl) -propyl] -acetamide,

2-cyano-N-cyclo-exyl-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) - ylidene] -acetamdie,

4- {2-Cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth- (E / Z) -ylidene] -thiazolidine (2-

(E or Z)) - ylidenes] -acetylamino} -piperidine-1-carboxylic acid ethyl ester,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- (3-hydroxy-propyl) -acetamides, 2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) - ylidenes] - N - (4-methoxy-benzyl) -acetamides,

2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes] -N- [2- (4-hydroxy-phenyl) -ethyl] -acetamide, N-Allyl-2-cyano-2 ~ [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idynes ] -acetamides, 2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idenes ] -N- (2-hydroxyethyl) acetamides, 2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] thiazolidine ( 2- (E or Z)) - ylidenes] - N - (4-hydroxybutyl) acetamides; 2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth- (E / Z) -ylidene] thiazolidine (2- (E or)) - ylidenes] - N - (6-hydroxy-hexyl) -acetamides, 2-cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idenecenoacetamides, 2-cyano-N-ethyl-2- [3-ethyl-4- oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) -idylenes] -acetamides, 2-cyano-2- [3-ethyl-5- [1- (4-methoxy-phenylamino) -methyl- (E / Z) -ylidene] -4-oxo-thiazolidine (2- (E or Z)) - ylidenes] -N, N-dimethyl-acetamides, 2 -Cyano-2- [3-ethyl-4-oxo-5- [1-phenylamino-meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) - ylidenes] -N, N dimethyl acetamide, 6 - {[2- [1 -C yano-1-dimethylcarbamoyl-meth- (E or Z) -ylidene] -3-ethyl-4-oxothiazolidine (5- (E / Z)) -ylidenemethyl] -amino} -naphthalenes-2-carboxylic acid, 4 - {[2- [1-Cyano-1-dimethylcarbamoyl-meth (E or Z) -ylidene] -3-ethyl-4-oxothiazolidine (5- (E / Z)) -ylidenemethyl] -amino } -benzoic acid, 2-cyano-2- [3-ethyl-5- [1- (4-hydroxy-phenylamino) -methyl- (E / Z) -ylidene] -4-oxo-thiazolipid (2 - (E or Z)) - ylidenes] - N, N-dimethyl-acetamides, 4 - {[2- [1-cyano-1-dimethylcarbamoyl-meth (E or Z) -ylidene] -3-ethyl-4 oxo thiazolidine (5- (E / Z)) ylidenemethyl] amino} benzamides, 2-cyano-2- [3-ethyl-5- [1- (4-hydroxymethylphenylamino) meth ( E / Z) -ylidene] -4-oxo-thiazolidine (2- (E or Z)) - ylidenes] -N, N-dimethyl-acetamides.

2. Compounds of general formula I, according to claim 1, in which Q is phenyl, naphthyl, quinolinyl, benzimidazolyl, indolyl, indazolyl, thiazolyl, imidazolyl or pyridyl, A and B are independently hydrogen, halogen, hydroxy, amino or nitro or optionally one or more times, the same or different with halogen, hydroxy, C ₃ -C ₆ heterocycloalkyl or with the group -NR ³ R ⁴ or -CO (NR ³ ) -M substituted dC ₃ alkyl or C -C ₆ alkoxy, wherein the heterocycloalkyl itself is optionally substituted by one or more nitrogen, oxygen and / or sulfur atoms may be interrupted and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring may be interrupted and / or optionally contain one or more double bonds in the ring can be and / or the ring itself optionally substituted one or more times, identically or differently, with C -Cβ alkyl, C ₃ -C ₆ cycloalkyl, Cι-C ₆ hydroxyalkyl or with the group - may be substituted NR ³ R ⁴ , or for -NR ³ (CO) -L, -NR ³ (CO) -NR ³ -L, -COR ⁶ , -CO (NR ³ ) -M, - NR ³ (CS) NR ³ R ⁴ , -NR ³ SO ₂ -M, -SO ₂ -NR ³ R ⁴ or - SO ₂ (NR ³⁾ are -M, L stands for optionally substituted one or more times, identically or differently, with Ci-C _δ hydroxyalkoxy, Cι-C ₆ - Alkoxyalkoxy, C ₃ -C ₃ - heterocycloalkyl or with the Group -NR ³ R ^4, substituted d- C _θ alkyl, or heteroaryl, wherein the heterocycloalkyl may itself be optionally interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally substituted by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally one or more times, same or different with -CC ₆ alkyl, C ₃ -C ₆ -cycloalkyl, -CC ₆ -hydroxyalkyl or with the group - NR ³ R ⁴ may be substituted, M is optionally one or more times, identically or differently with the group -NR ³ R ⁴ or C ₃ -C ₆ -Heterocycloalkyl substituted -CC ₆ alkyl, X is -NH- or -NR ⁵ -, R ^{1 is} optionally mono- or polysubstituted by identical or different halogen-substituted C ₁ -C 4 -alkyl, C ₃ -cycloalkyl, allyl or propargyl, R ^{2 is} hydrogen or optionally mono- or polysubstituted, identical or different, with halogen, hydroxyl, cyano, C ₆ alkyl, Ci-Ce-alkoxy, Cι-C ₆ hydroxyalkyl, C ₃ -C ₆ - cycloalkyl, C ₃ -C ₆ heterocycloalkyl, C ₃ -C alkynyl, aryl, aryloxy, heteroaryl or Ci-Cβ-alkyl, CC ₆ -alkoxy substituted with the group -S-C ₁ -C ₆ -alkyl, -COR ⁶ , -NR ³ R ⁴ , -NR ³ (CO) -L or -NR ³ COOR ⁷ , Ci-Cβ-alkenyl, Cι-C ₆ alkynyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ - heterocycloalkyl, aryl or heteroaryl, wherein the heterocycloalkyl itself optionally substituted by one or more nitrogen, oxygen and / or sulfur Atoms may be interrupted and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or may optionally contain one or more double bonds in the ring se in can and wherein aryl, heteroaryl, C ₃ -C 6 cycloalkyl and / or C ₃ - Cβ-heterocycloalkyl ring in each case itself optionally substituted one or more times, identically or differently, with cyano, halogen, hydroxy, Cι-C ₃ alkyl, Cι-C ₆ hydroxyalkyl, optionally mono- or polysubstituted by identical or different halogen substituted with Cι-C ₆ -alkoxy, C ₃ -C ₆ cycloalkyl, C ₃ -Cβ- heterocycloalkyl, aryl, benzyl or heteroaryl may be substituted, or the group -NR ³ R ⁴ , -NR ³ (CO) -L, -NR ³ (CS) NR ³ R ⁴ , or R ² and R ⁵ together form a C ₃ -Cβ heterocycloalkyl ring which is at least once is interrupted by nitrogen and may optionally be interrupted one or more times by oxygen or sulfur and / or optionally by one or more - (CO) - or -SO ₂ - groups in the ring may be interrupted and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally one or more times, same or different with cyano, halogen, hydroxy, -CC ₆ - alkyl, C ₃ -C ₆ can be cycloalkyl, Cι-C ₆ hydroxyalkyl, CC ₆ alkoxyalkyl or substituted with the group -NR ³ R ⁴ or -COR ⁶ and / or mono- or polysubstituted with optionally, identically or differently with halogen, Cι-C ₆ Alkoxy or with the group - COR ⁶ substituted aryl or heteroaryl may be substituted, R ³ and R ^{4 are} independently hydrogen or optionally mono- or polysubstituted, identical or different with halogen, hydroxy, C ₃ -C 6 heterocycloalkyl, C 1 -C 8 -hydroxyalkoxy or C 1 -C ₆ -alkyl substituted with the group -NR ³ R ⁴ , C 1 -C ₆ -alkoxy, -CO-C 1 -C ₆ -alkyl or aryl, where the heterocycloalkyl itself is optionally substituted by one or more nitrogen, oxygen and / or or sulfur atoms interrupted s one and / or optionally may be interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C ₆ -Heterocycloalkylring itself in each case optionally mono- or polysubstituted, identically or differently, with cyano, halogen, Cι-C ₆ -alkyl, C ₆ hydroxyalkyl, Cι-C _θ - alkoxy, C ₃ -C ₆ cycloalkyl, or with the group -NR ³ R ⁴ or - CO-NR ³ R ⁴ may be substituted, or R ³ and R ⁴ together form a C ₃ -C ₆ heterocycloalkyl ring which is interrupted at least once by nitrogen and optionally interrupted one or more times by oxygen or sulfur and / or may optionally be interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and / or the heterocycloalkyl ring itself optionally substituted one or more times, identically or differently, with CrC ₆ alkyl, C ₃ -C ₆ - cycloalkyl, Cι-C ₆ hydroxyalkyl, Cι-C ₆ alkoxyalkyl, cyano, hydroxy or with the group -NR ³ R ⁴ may be substituted, R ⁵ is optionally substituted one or more times, identically or differently with halogen, hydroxy, cyano, C ₆ alkoxy, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ heteroalkyl cycloalkyl, or with the group -NR ³ R ⁴ substituted -CC ₆ alkyl, -CC ₆ alkenyl, -CC ₆ alkynyl, wherein the heterocycloalkyl itself is optionally substituted by one or more nitrogen, oxygen and / or sulfur Atoms may be interrupted and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C ₆ Heterocycloalkyl ring itself in each case optionally mono- or polysubstituted, identically or differently, with cyano, halogen, Cι-C ₆ -alkyl, C ₆ hydroxyalkyl, Cι-C ₆ - alkoxy, C ₃ -C ₆ cycloalkyl, or with the group -NR ³ R ⁴ or - may be substituted CO-NR ³ R ^4, R ^{6 is} hydroxy, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy or the group -NR ³ R ⁴ , R ^{7 is} - (CH ₂ ) _n -aryl or - (CH ₂ ) _n -heteroaryl and n is 1 to 6, and their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.

3. Compounds of general formula I, according to claim 1 or 2, in which Q is phenyl, naphthyl or indolyl, A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted by identical or CC ₃ alkyl substituted with halo, hydroxy, C ₃ -C ₆ heterocycloalkyl, or -NR ³ R ⁴ or -CO (NR ³ ) -M group or Ci-Cβ-alkoxy, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by one or more - (CO) - or -SO ₂ - groups in the ring may be interrupted and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally one or more times, the same or different with -CC ₆ alkyl, C ₃ -C ₆ cycloalkyl, -CC ₆ -Hydroxyalkyl or with the group --NR ³ R ⁴ , or for -NR ³ (CO) -L, -NR ³ (CO) -NR ³ -L, -COR ⁶ , -CO (NR ³ ) - M, - NR ³ (CS) NR ³ R ⁴ , -NR ³ SO ₂ -M, -SO ₂ -NR ³ R ⁴ or -SO ₂ (NR ³ ) -M, L is optionally one or more times, the same or C -C ₆ -alkyl or heteroaryl substituted by C ₁ -C ₆ -hydroxyalkoxy, C ₁ -C ₆ -alkoxyalkoxy, C ₃ -C ₆ -heterocycloalkyl or by the group -NR ³ R ⁴ , where the heterocycloalkyl itself is optionally substituted by an or a plurality of nitrogen, oxygen and / or sulfur atoms may be interrupted and / or may optionally be interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself may optionally be mono- or polysubstituted, identically or differently, with C ₁ -C ₆ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₁ -C ₆ -hydroxyalkyl or with the group --NR ³ R ⁴ , M is optionally mono- or polysubstituted, identically or differently, with the group -NR ³ R ⁴ or C ₃ -C ₆ heterocycloalkyl substituted Cι-C ₆ -alkyl,

X is -NH- or -NR ⁵ -,

R ^{1 represents} optionally mono- or polysubstituted by identical or different halogen-substituted C 1 -C 4 -alkyl, C ₃ -cycloalkyl, allyl or propargyl, 3O0

R ² represents hydrogen or represents optionally mono- or polysubstituted, identically or differently with halogen, hydroxy, cyano, C ₆ -alkyl, d-Ce-alkoxy, Ci-Cβ hydroxyalkyl, C ₃ -C ₆ - cycloalkyl, C ₃ -C ₆ heterocycloalkyl, Cι-C ₆ alkynyl, aryl, aryloxy, heteroaryl or with the group -S-Ci-Ce-alkyl, -COR ^6, -NR ³ R ^4, -NR ³ (CO) - L or -NR ³ COOR ^{7-substituted} Ci-Cβ alkyl, Ci-Cβ- alkoxy, d-Cβ-alkenyl, dC ₆ alkynyl, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ - heterocycloalkyl, aryl or heteroaryl where the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds may be contained in the ring and wherein aryl, heteroaryl, C ₃ -C ₆ cycloalkyl and / or the C ₃ - C ₆ heterocycloalkyl ring each themselves optionally optionally one or more times, the same ch or differently, with cyano, halogen, hydroxy, Cι-C ₆ -alkyl, C ₆ hydroxyalkyl, optionally mono- or polysubstituted by identical or different halogen substituted with Cι-C ₆ alkoxy, C ₃ -C ₆ -Cycloaikyl , C ₃ -C ₆ heterocycloalkyl, aryl, benzyl or heteroaryl, or the group -NR ³ R ⁴ , -NR ³ (CO) -L, -NR ³ (CS) NR ³ R ⁴ , or

R ² and R ⁵ together form a C ₃ -C ₆ heterocycloalkyl ring which is interrupted at least once by nitrogen and may optionally be interrupted once or several times by oxygen or sulfur and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally one or more times, same or different with cyano, halogen, hydroxy, -C-C ₆ - Alkyl, C ₃ -C ₆ -cycloalkyl, Ci-Ce-hydroxyalkyl, -CC ₆ -alkoxyalkyl or with the group -NR ³ R ⁴ or -COR ⁶ may be substituted and / or optionally with one or more times, the same or may be substituted by halogen, C ₁ -C ₆ -alkoxy or by the group --COR ⁶ -substituted aryl or heteroaryl

R ³ and R ⁴ independently of one another represent hydrogen or optionally mono- or polysubstituted, identically or differently, with halogen, hydroxyl, C ₃ -C ₆ -heterocycloalkyl, dC ₆ -hydroxyalkoxy or -substituted with the group -NR ³ R ⁴ Cβ-alkyl, C -C -alkoxy, -CO-C -C ₆ -alkyl or aryl, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by a or several - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C ₆ -Heterocycloalkylring itself each optionally one or more times, the same or differently, with cyano, halogen, _Cι-C6 alkyl, Ci-Ce-hydroxyalkyl, dC ₆ - alkoxy, C ₃ -C ₆ cycloalkyl, or with the group -NR ³ R ⁴ or - CO-NR ³ R ⁴ or R ³ and R ⁴ together form a C ₃ -C ₆ heterocycloalkyl ring bi Lden, which is interrupted at least once by nitrogen and may optionally be interrupted by one or more times by oxygen or sulfur and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds in the ring can be contained and / or the heterocycloalkyl ring itself optionally mono- or polysubstituted, identically or differently with C ₆ alkyl, C ₃ -C ₆ - cycloalkyl, Cι-C ₆ hydroxyalkyl, Ci-Ce-alkoxyalkyl , Cyano, hydroxy or may be substituted by the group -NR R ⁴ , R ⁵ is optionally substituted one or more times, identically or differently with halogen, hydroxy, cyano, dC ₆ alkoxy, C ₃ -C ₆ cycloalkyl, C ₃ -C ₆ heterocycloalkyl, or substituted with the group -NR ³ R ⁴ dC ₆ alkyl, Ci-Ce-alkenyl, Cι-C is ₆ -alkynyl, where the heterocycloalkyl itself optionally substituted by one or more nitrogen, oxygen and / or sulfur atoms can be interrupted and / or optionally substituted by one or more - ( CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -Cβ heterocycloalkyl itself each optionally one or more times, same or different with cyano, halogen, C -Ce-alkyl, Ci-Ce-hydroxyalkyl, Cι-C ₆ - alkoxy, C ₃ -C ₆ cycloalkyl, or with the group -NR ³ R ⁴ or - may be substituted CO-NR ³ R ^4, R ^{6 is} hydroxy, C 1 -C ₆ -alkyl, C -C -alkoxy or the group -NR ³ R ⁴ , R ^{7 is} - (CH ₂ ) _n -aryl or - (CH ₂ ) _n Heteroaryl and n is 1-6, as well as their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.

4. Compounds of general formula I, according to one of the preceding claims, in which Q is phenyl, naphthyl or indolyl, A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted, the same or differently with pyrrolidinyl, piperidinyl, piperazinyl or with the group - N (-CC ₆ alkyl) ₂ or -CO (NH) -M substituted CC ₃ alkyl or -CC ₆ alkoxy, wherein pyrrolidinyl, piperidinyl or Piperazinyl itself optionally one or more times, identical or different with Ci-Cβ-alkyl or Ci-Ce-hydroxyalkyl or -CO (NH) -M, -CO (NCH ₃ ) -M, -NH (CO) -L, -NH (CO) -NH-L-SO ₂ (NH) -M, or - SO ₂ (M CH ₃ ) -M, L is optionally mono- or polysubstituted by identical or different substituents with C ₁ -C ₆ -hydroxyalkoxy, C ₁ -C ₆ -alkoxyalkoxy, pyrrolidinyl, piperazinyl or with the group -N (C ₁ -C ₆₎ Alkyl) ₂ substituted C 1 -C 6 -alkyl or pyridyl, where the pyrrolidinyl or piperazinyl itself may optionally be monosubstituted or polysubstituted, identically or differently, by C 1 -C 6 -alkyl,

M is optionally mono- or polysubstituted, identically or differently with the group -N (-CC ₆ -alkyl) ₂ or pyrrolidinyl-substituted Ci-Cβ-alkyl, X is -NH- or -NR ⁵ -, R ^{1 is} optionally mono- or polysubstituted by identical or different halogen-substituted -CC alkyl, R ^{2 is} hydrogen or optionally mono- or polysubstituted, identical or different with halogen, hydroxy, cyano, -CC ₆ alkyl, -C C ₃ alkoxy, C ₁ -C ₆ hydroxyalkyl, C ₃ -C ₆ cycloalkyl, tetrahydrofuranyl, pyrrolidinyl, piperazinyl, morpholinyl, phenyl, phenoxy, biphenyl, naphthyl, thienyl, furanyl, tetrazolyl, pyridyl or with the group -S- Cι-C ₆ alkyl, -CONH _2, _-COO-Cι-C3 alkyl, -N _(Cι-C6 alkyl) _2, -N (Cι-C ₆ - alkyl) phenyl, -NH (CO) -L substituted Ci-Ce-alkyl, Cι-C ₆ - alkenyl, Ci-Cβ alkynyl, C ₃ -C ₆ cycloalkyl, pyrrolidinyl, piperidinyl, phenyl, tetralinyl or indolyl, with phenyl, furanyl, C ₃ -C ₆ -cycloalkyl, piperidinyl or piperazinyl in each case s ven optionally mono- or polysubstituted, identically or differently, with dC ₆ alkyl, dC ₆ alkoxy, cyano, halogen, hydroxy, phenyl, benzyl, morpholinyl and may be substituted _Cι-C6 alkyl or Cι-C ₆ alkoxy may optionally be mono- or polysubstituted by identical or different substituents with halogen, or the group is -N (CγC ₆ -alkyl) ₂ , -NH (CO) -L, -NCH ₃ (CS) NHCH ₃ , or R ² and R ⁵ together form aziridinyl, azetidinyl, morpholinyl, pyrrolidinyl, piperidinyl or piperazinyl where aziridinyl, azetidinyl, morpholinyl, pyrrolidinyl, piperidinyl or piperazinyl itself optionally one or more times, same or different with hydroxy, Ci-Ce-alkyl, Ci-Ce-hydroxyalkyl, Ci-Ce-alkoxyalkyl or with the group -CONH ₂ , -CO-C 1 -C 6 -alkyl or -COO-C 1 -C 6 -alkyl and / or may be substituted by optionally mono- or polysubstituted by identical or different substituents with halogen or C 1 -C 6 -alkoxy-substituted phenyl, benzyl or pyridyl can, and R ^{5 is} optionally mono- or polysubstituted by identical or different Ci-Cβ-alkoxy-substituted Ci-Cβ-alkyl or -CC ₆ alkenyl, and their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.

Compounds of the general formula (I) according to the preceding claims, in which Q is phenyl, naphthyl or indolyl,

A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted, identically or differently, with pyrrolidinyl, piperidinyl, piperazinyl or with the group --N (CH ₃ ) ₂ or --CO (NH) - (CH ₂ ) 2-N (CH ₃ ) ₂ substituted CC ₃ - alkyl or -CC ₃ alkoxy, where pyrrolidinyl, piperidinyl or piperazinyl itself optionally one or more times, same or different, with -CC ₃ alkyl or C ₁ -C ₃ -hydroxyalkyl may be substituted, or for the group -CO-NH- (CH ₂₎ ₂ -N (CH ₃₎ _2, -CO-NH- (CH ₂₎ ₂ - N (C ₂ H ₅₎ _2, -CO-N (CH ₃₎ - (CH ₂ ) ₂ -N (CH ₃ ) ₂ ,

or -SO ₂ -NH- (CH ₂ ) ₂ -N (CH ₃ ) ₂ or -SO ₂ -N (CH ₃ ) - (CH ₂ ) ₂ -N (CH ₃ ) ₂ ,

X is -NH- or -NR ⁵ -,

R ^{1 represents} optionally mono- or polysubstituted by identical or different halogen-substituted C ₁ -C ₃ -alkyl,

R ^ represents hydrogen or represents optionally mono- or polysubstituted, identically or differently with halogen, hydroxy, cyano, CrC ₆ - alkyl, Cι-C ₆ hydroxyalkyl, methoxy, C ₃ -C ₆ cycloalkyl, tetrahydrofuranyl, pyrrolidinyl, piperazinyl, Morpholinyl, phenyl, phenoxy, biphenyl, naphthyl, thienyl, furanyl, tetrazolyl or pyridyl or with the group -S-CH ₃ , -COOCH ₃ , -COOC ₂ H ₅ , -CO-NH ₂ , -OCF ₃ , -N (CH ₃₎ -phenyl, -N _(Cι-C4 alkyl) _2, -NH (CO) _{-CH3-substitu} iertes Ci-Ce-alkyl, dC ₄ alkenyl, Cι-C ₄ - alkynyl, C ₃ C ₆ -cycloalkyl, piperidinyl, phenyl, pyrolidinyl, indolyl or tetralinyl, where phenyl, furanyl, C ₃ -C ₆ -cycloalkyl, Piperidinyl or piperazinyl optionally each themselves one or more times, identically or differently with cyano, halogen,

Hydroxy, -CC ₃ -alkyl, -CC ₃ -hydroxyalkyl, methoxy, morpholinyl

Phenyl or benzyl, or for the group -N (CH ₃ ) ₂ , -N (CH ₃ ) (CS) NHCH ₃ , -NH (CO) -CH ₃ , -

NH (CO) pyridyl, -NH (CO) pyridinyl, or

R ² and R ⁵ together form one of the following rings

R is optionally monosubstituted or polysubstituted, identically or differently with C ₁ -C ₆ -alkoxy-substituted C ₁ -C ₃ -alkyl or C ₁ -C ₃ -alkenyl, and also their solvates, hydrates, stereoisomers, diastereomers,

Enantiomers and salts.

6. Compounds of the general formula IA

in the

Q is aryl or heteroaryl,

A and B independently of one another are hydrogen, halogen, hydroxyl, amino or nitro or optionally mono- or polysubstituted by identical or different substituents with halogen, hydroxy, C ₃ -C ₆ -heterocycloalkyl or with the group -NR ³ R ⁴ or - CO (NR ³ ) -M substituted -C 1 -C ₃ alkyl or -CC ₆ alkoxy, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by a or several - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the ring itself optionally one or more times, same or different with CrC ₆ - Alkyl, C ₃ -Ce-cycloalkyl, Ci-Cβ-hydroxyalkyl or with the group - NR ³ R ⁴ may be substituted, or for -NR ³ (CO) -L, -NR ³ (CO) -MR ³ -L, -COR ⁶ , -CO (NR ³ ) -M, - NR ³ (CS) NR ³ R ⁴ , -NR ³ SO ₂ -MI, -SO ₂ -NR ³ R ⁴ or -SO ₂ (NR ³ ) -M stand s, L is optionally substituted one or more times, identically or differently, with d-Cβ-hydroxyalkoxy, Cι-C ₆ alkoxyalkoxy, C ₃ -C ₆ - heterocycloalkyl or with the group -NR ³ R ^4, substituted Ci- C ₆ - Alkyl or heteroaryl, wherein the heterocycloalkyl itself optionally interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally interrupted by one or more - (CO) - or -SO ₂ - groups in the ring and / or optionally one or more double bonds in the Ring may be included and / or the ring itself optionally one or more times, same or different with -CC ₆ alkyl, C ₃ -C ₆ cycloalkyl, Ci-Cβ-hydroxyalkyl or substituted with the group - NR ³ R ⁴ may be, is mono- or M is optionally more times, identically or differently, with the group -NR ³ R ⁴ or C ₃ -C ₆ heterocycloalkyl substituted Cι-C ₆ -alkyl, R ¹ is mono- or polysubstituted optionally, C 1 -C -alkyl, C ₃ -Cycloalkyl, allyl or propargyl which is identical or different with halogen,

R ^{2a is} allyl or propargyl,

R ³ and R ⁴ are independently hydrogen or one is optionally substituted one or more times, identically or differently with halogen, hydroxy, C ₃ -C ₆ heterocycloalkyl, dC ₆ - hydroxyalkoxy or substituted with the group -NR ³ R ⁴ Ci- Ce-alkyl, Ci-Cβ-alkoxy, -CO-C-C ₆ alkyl or aryl, wherein the heterocycloalkyl itself may optionally be interrupted by one or more nitrogen, oxygen and / or sulfur atoms and / or optionally by a or several - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and wherein the C ₃ -C ₆ -Heterocycloalkylring itself each optionally one or more times, the same or differently, with cyano, halogen, Ci-Ce-alkyl, Ci-Ce-hydroxyalkyl, Cι-C _β - alkoxy, C ₃ -C ₆ cycloalkyl, or with the group -NR ³ R ⁴ or - CO-NR ³ R ⁴ may be substituted, or R ³ and R ⁴ together form a C ₃ -C ₆ -heterocycloalkyl ring which is interrupted at least once by nitrogen and may optionally be interrupted by one or more times by oxygen or sulfur and / or optionally by one or more - (CO) - or -SO ₂ - groups may be interrupted in the ring and / or optionally one or more double bonds may be contained in the ring and / or the heterocycloalkyl ring itself optionally one or more times, same or different with Ci-Ce-alkyl, C ₃ -C ₆ - cycloalkyl, Ci-Cβ-hydroxyalkyl, Ci-Ce-alkoxyalkyl, cyano, hydroxy or with the group -NR ³ R ⁴ may be substituted, and R ^{6 is} hydroxy, C _r C ₆ alkyl, Ci-Ce-alkoxy or the group -NR ³ R ⁴ , and their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.

7. Compounds of general formula IA, according to claim 6, in which Q is phenyl, quinolinyl, indolyl or naphthyl, A and B independently of one another are hydrogen or halogen or optionally mono- or polysubstituted, identical or different, with halogen, hydroxy or with the group -NC Cβ-alkyl) ₂ or -CO (NH) -M substituted -C-C ₃ alkyl or Ci-Ce-alkoxy or -NH (CO) -L, -NH (CO) -NH -L, -COR ⁶ , -CO (NH) -M, --CO (NCH ₃ ) -M, -SO ₂ (NH) -M or -SO ₂ (NCH ₃ ) -M, L is optionally on or is monosubstituted, identically or differently pyrrolidinyl-substituted dC ₆ -alkyi, M is optionally mono- or polysubstituted by identical or different substituents with the group -M (C 1 -C 6 -alkyl) ₂ or pyrrolidinyl-substituted C 1 -C ₆ -alkyl, R ¹ is C ₁ -C ₃ -alkyl, R ^{2a is} allyl or propargyl, R ^{6 is} hydroxy, C 1 -C ₆ -alkyl or C 1 -C ₆ -alkoxy, and also their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.

Compounds of the following formulas, as well as their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts: (E or Z) -cyano- (3-ethyl-5- (E / Z) - {[4- (2-morpholine-4 -yl-ethanesulfonylamino) -phenylamino] -methylene} -4-oxo-thiazolidin-2-ylidenes) -acetic acid ethyl ester, (E or Z) -cyano- [3-ethyl-4-oxo-5- (E) Z) - ({4 - [(pyrrolidine-1-carbonyl) -amino] -phenylamino} -methylene) -thiazolidin-2-ylidenes] -acetic acid ethyl ester,

(E or Z) -cyano- (3-ethyl-5- (E / Z- ({4- [3- (4-methylpiperazin-1-yl) -propionylamino] -phenylamino} -methylene} -4- oxo-thiazolidin-2-ylidene) -essigsäureallylester,

(E or Z) -cyano- (3-ethyl-5- (E / Z- ({4- [3- (4-methylpiperazin-1-yl) -propionylamino] -phenylamino} -methylene} -4- oxo-thiazolidin-2-ylidene) -acetic acid benzyl ester, (E or Z) -cyano- (3-ethyl-5- (E / Z) - {[4- (2-pyrrolidin-1-yl-ethylcarbamoyl) -phenylamino] -methylene} -4-oxo-thiazolidin-2-ylidene) -acetic acid allyl ester, (E or Z) -cyano- [3-ethyl-4-oxo-5- (E / Z) - (p-tolylamino-methylene) - thiazolidin-2-ylidenes] -acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-4-oxo-5- (E / Z) - (m-tolylamino-methylene) -thiazolidin-2-ylidenes] -acetic acid ethyl ester,

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(3-nitro-phenylamino) -methylene] -4-oxo-thiazolidin-2-ylidene} -acetic acid ethyl ester,

(E or Z) - {5- (E / Z) - [(3-chloro-phenylamino) -methylene] -3-ethyl-4-oxo-thiazolidin-2-ylidenes} -cyano-acetic acid ethyl ester, 5 - {[2 - ((E or Z) -cyano-ethoxycarbonyl-methylene) -3-ethyl-4-oxo-thiazolidine-5]

(E / Z) -ylidenemethyl] -amino} -1H-indole-2-carboxylic acid ethyl ester, (E or Z) -cyano- {3-ethyl-5- (E / Z) - [(2-methyl -1H-indol-5-ylamino) -methylene] -4-oxo-thiazolidin-2-ylidene} -acetic acid ethyl ester,

(E or Z) - {5- (E / Z) - [(3-carbamoyl-1H-indol-5-ylamino) -methylene] -3-ethyl-4-oxo-thiazolidin-2-ylidenes} -cyano- acetic acid ethyl ester,

(E or Z) -cyano- (3-ethyl-5- (E / Z) - {[3- (4-methylpiperazine-1-carbonyl) -phenylamino] -methylene} -4-oxo-thiazolidine-2 -ylidene) -acetic acid ethyl ester, (E or Z) -cyano- [3-ethyl-5- (E / Z) - ({3- [2- (2-hydroxymethylpyrrolidin-1-yl) -ethanesulfonylamino] ] phenylamino} -methylene) -4-oxo-thiazolidin-2-ylidene] - acetic acid ethyl ester,

(E or Z) -Cyano- (3-ethyl-4-oxo-5- (E / Z) - {[3- (2-piperidin-1-yl-ethanesulfonylamino) -phenyl-amino] -methylene} -thiazolidine-2 -ylidene) -acetic acid ethyl ester, (E or Z) -cyano- (3-ethyl-4-oxo-5- (E / Z) - {[3- (2-pyrrolidin-1-yl-ethanesulfonylamino) - phenylamino] -methylene} -thiazolidin-2-ylidenes) -acetic acid ethyl ester,

(E or Z) -cyano- (3-ethyl-5- (E / Z) - {[4- (3-methoxy-propionylamino) -phenylamino] -methylene} -4-oxo-thiazolidin-2-ylidenes) - acetic acid ethyl ester, (E or Z) -cyano- [3-ethyl-5- (E / Z) - ({4- [2- (2-methoxy-ethoxy) -acetylamino] -phenylamino} -methylene) - 4-oxo-thiazolidin-2-ylidenes] -acetic acid ethyl ester,

(E or Z) -cyano- (3-ethyl-5- (E / Z) - {[4- (2-methoxy-acetylamino) -phenylamino] -methylene} -4-oxo-thiazolidin-2-ylidenes) - acetic acid ethyl ester,

(E or Z) -Cyano- (3-ethyl-4-oxo-5- (E / Z) - {[4- (2-piperidin-1-yl-ethanesulfonyl-amino) -phenyl-amino] -methylene} -thiazolidine-2 -ylidene) -acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-5- (E / Z) - ({4- [2- (4-methylpiperazin-1-yl) -ethanesulfonylamino] -phenylamino} -methylene) -4 -oxo-thiazolidin-2-ylidenes] - acetic acid ethyl ester, (E or Z) -cyano- {3-ethyl-5- (E / Z) - [(4-methanesulfonylamino-phenylamino) -methylene) -4- oxo-thiazolidin-2-ylidene} -acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-5- (E / Z) - ({4- [2- (2-hydroxymethyl-piperidin-1-yl) -ethanesulfonylamino] -phenylamino} -methylene) -4 -oxo-thiazolidin-2-ylidenes] - acetic acid ethyl ester, (E or Z) -cyano- [3-ethyl-5- (E / Z) - ({4- [2- (2-hydroxymethyl-pyrrolidine) 1-yl) -ethanesulfonylamino] -phenylamino} -methylene) -4-oxo-thiazolidin-2-ylidenes] - acetic acid ethyl ester,

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(4-hydroxy-phenylamino) -methylene] -4-oxo-thiazolidin-2-ylidene} -acetic acid propyl ester, ( E or Z) -cyano- {3-ethyl-5- (E / Z) - [(2-fluoro-4-hydroxy-phenylamino) -methylene] -

4-oxo-thiazolidin-2-ylidenes -acetic acid ethyl ester,

(E or Z) - {5- (E / Z) - [(3-chloro-4-hydroxy-phenylamino) -methylene] -3-ethyl-4-oxo-thiazolidin-2-ylidenes} cyano-acetic acid ethyl ester,

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(4-hydroxy-3-nitro-phenylamino) -methylene] - 4-oxo-thiazolidin-2-ylidenes -acetic acid ethyl ester,

(E or Z) -cyano- {5- (E / Z) - [(3,5-dichloro-4-hydroxy-phenylamino) -methylene] -3-ethyl-4-oxo-thiazolidin-2-ylidenes} - acetic acid ethyl ester,

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(4-hydroxy-3,5-dimethylphenylamino) methylene] -4-oxo-thiazolidin-2-ylidenes} - acetic acid ethyl ester,

(E or Z) -cyano- {5- (E / Z) - [(3-diethylaminomethyl-4-hydroxy-phenylamino) methylene] -3-ethyl-4-oxo-thiazolidin-2-ylidene} -acetic acid ethyl ester,

(E or Z) -Cyano- {3-ethyl-5- (E / Z) - [(4-hydroxy-3-methylphenylamino) methylene] -4-oxo-thiazolidin-2-ylidene} -acetic acid ethyl ester, (E or Z) -cyano- {5- (E / ZH (3,5-dibromo-4-hydroxy-phenylamino) -methylene] -3-ethyl-4-oxo-thiazolidin-2-ylidenes} - acetic acid ethyl ester,

5 - {[2 - ((E or Z) -cyano-ethoxycarbonyl-methylene) -3-ethyl-4-oxo-thiazolidine-5]

(E / Z) -ylidenemethyl] amino} -2-hydroxy-benzoic acid methyl ester,

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(2-hydroxy-phenylamino) -methylene] -4-oxo-thiazolidin-2-yl-idene} -acetic acid ethyl ester .

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(2-fluoro-phenylamino) -methylene] -4-oxo-thiazolidin-2-ylidenes} -acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-4-oxo-5- (E / Z) - (o-tolylamino-methylene) -thiazolidin-2-ylidenes] -acetic acid ethyl ester, (E or Z) - {5- (e / Z) - [(2-chloro-phenylamino) -methylene] -3-ethyl-4-oxo-thiazolidine

2-ylidenes-cyano-acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-4-oxo-5- (E / Z) - (quinolin-8-yl-amino-methylene) -thiazolidin-2-ylidenes] -acetic acid ethyl ester,

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(2-isopropyl-phenylamino) -methylene] -4-oxo-thiazolidin-2-ylidenes} -acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-5- (E / Z) - (naphthalen-1-ylaminomethylene) -4-oxothiazolidin-2-ylidenes] -acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-5- (E / Z) - (naphthalen-1-ylaminomethylene) -4-oxothiazolidin-2-ylidenes] -acetic acid ethyl ester, (E or Z) -Cyano- {3-ethyl-5- (E / Z) - [(2-ethylphenylamino) -methylene] -4-oxothiazolidin-2-ylidenes} -acetic acid ethyl ester,

(E or Z) - {5- (E / Z) - [(1H-Benzoimidazol-2-ylamino) -methylene] -3-ethyl-4-oxo-thiazolidin-2-ylidene} -cyano-acetic acid ethyl esters,

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(1-methyl-1H-benzoimidazole-2-ylamino) - methylene] -4-oxo-thiazolidin-2-ylidenes -acetic acid ethyl ester, cyano- [3-ethyl-4-oxo-5- [1- [4- (3-pyrrolidin-1-yl-propionylamino) - phenylamino] - meth (E / Z) -ylidene] -thiazolidine (2- (E or Z)) - ylidenes] -acetic acid allyl esters, cyano- [3-ethyl-4-oxo-5- [1-] {4- [3- (2-pyrrolidin-1-yl-ethyl) -ureido] -phenylamino} -meth- (E / Z) -ylidene] -thiazolidine (2- (E or Z)) - ylidenes] - acetic acid allyl ester,

4- (4 - {[2- [1-Allyloxycarbonyl-1-cyano-meth (E or Z) -ylidene] -3-ethyl-4-oxothiazolidine-5- (E / Z) -ylidenemethyl] - amino} -phenyl) -butyric acid, cyano- [3-ethyl-4-oxo-5- [1- [3- (3-pyrrolidin-1-yl-propionylamino) -phenylamino] -meth- (E / Z) -ylidene] thiazolidine (2- (E or Z)) - ylidenes] -acetic acid allyl esters, 4 - {[2- [1-allyloxycarbonyl-1-cyano-meth (E or Z) -ylidene] - 3-ethyl-4-oxothiazolidine-5- (E / Z) -ylidenemethyl] -amino} -benzoic acid, 6 - {[2- [1-allyloxycarbonyl-1-cyano-meth (E or Z) - ylidene] -3-ethyl-4-oxothiazolidine-5- (E / Z) -ylidenemethyl] -amino} -naphthalenes-2-carboxylic acid, cyano- [5- [1- {4- [3- (2 -diethylamino-ethylcarbamoyl) -propyl] -phenylamino} -methyl- (E / Z) -ylidene] -3-ethyl-4-oxo-thiazolidine (2- (E or Z)) -idene] -acetic acid allyl ester .

Cyano [3-ethyl-4-oxo-5- [1- [6- (2-pyrrolidin-1-yl-ethylcarbamoyl) -naphthalene-2-ylamino] -meth- (E / Z) -ylidene] -thiazolidine - (2- (E or Z)) - ylidenes] -acetic acid allyl esters, (E or Z) -cyano- [3-ethyl-5- (E / Z) - ({4- [3- (2- hydroxy-ethyl) -urido] -phenylamino} -methylene-4-oxo-thiazolidin-2-ylidene] -acetic acid ethyl ester, (E or Z) -cyano- [3-ethyl-4-oxo-5- (E) Z) - ({4 - [(pyrrolidine-1-carbonyl) -amino] -phenylamino} -methylene) -thiazolidin-2-ylidene] -acetic acid ethyl ester, (E or Z) -cyano- [3-ethyl-5- ( E / Z) - ({4-methoxy-3 - [(morpholine-4-carbothioyl) -amino] -phenylamino} -methylene) -4-oxo-thiazolidin-2-ylidene] -acetic acid ethyl ester,

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(4- {3- [2- (2-hydroxy-ethoxy) -ethyl] -ureido} -phenylamino) -methylene] 4-oxo-thiazolidin-2-ylidene} -acetic acid ethyl ester, (E or Z) -cyano- [3-ethyl-5- (E / Z) - ({4 - [(4-methylpiperazine-1-carbothioyl ) -amino] - phenylamino} -methylene) -4-oxo-thiazolidin-2-ylidene] -acetic acid ethyl ester, (E or Z) -cyano- [3-ethyl-5- (E / Z) - ({4- [3- (2-hydroxyethyl) thioureido] phenylamino} methylene) -4-oxo-thiazolidin-2-ylidene] acetic acid ethyl ester,

(E or Z) - {5- (E / Z) - [(4-acetylsulfamoyl-phenylamino) -methylene] -3-ethyl-4-oxo-thiazolidin-2-ylidene} -cyano-acetic acid ethyl ester,

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(4- {3- [2- (2-hydroxy-ethoxy) -ethyl] -thioureido} - phenylamino) methylene] -4-oxo-thiazolidin-2-ylidene} acetic acid ethyl ester, (E or Z) cyano (3-ethyl-5- (E / Z) - {[2- (2-hydroxy-ethyl ) -phenylamino] -methylene} - 4-oxo-thiazolidin-2-ylidene) -acetic acid ethyl ester,

Cyano {3-ethyl-5- (E / Z) - [(2-ethyl-phenylamino) -methylene] -4-oxo-thiazolidin-2-ylidene-1-acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-5- (E / Z) - ({4-fluoro-3- [3- (2-morpholin-4-yl-ethyl) -ureido] -phenylamino} - methylene) -4-oxo-thiazolidin-2-ylidene] -acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-5- (E / Z) - ({4- [3- (1-ethylpyrrolidin-2-ylmethyl) -ureido] -phenylamino} -methylene) -4 oxo-thiazolidin-2-ylidene] -acetic acid ethyl ester, (E or Z) -cyano- {3-ethyl-5- (E / Z) - [(4 - {[4- (2-hydroxy-ethyl) -piperazine 1-carbonyl] - amino} -phenylamino) -methylene] -4-oxo-thiazolidin-2-ylidene} -acetic acid ethyl ester, (E or Z) -cyano- [3-ethyl-5- (E / Z) - ( {3- [3- (2-morpholin-4-yl-ethyl) -ureido] -phenylamino} -methylene) -4-oxo-thiazolidin-2-ylidene-1-ethylacetate, (E or Z) -cyano- [5- (E / Z) - ({3- [3- (3-dimethylamino-propyl) -ureido] -phenylamino} -methylene) -3-ethyl-4-oxo-thiazolidin-2-ylidene] -acetic acid ethyl ester,

(E or Z) -cyano- {3-ethyl-5- (E / Z) - [(4 - {[4- (4-methyl-piperazin-1-yl) -piperidine-1-carbonyl] -amino} -phenylamino) -methylene] -4-oxo-thiazolidin-2-ylidene} - acetic acid ethyl ester,

(E or Z) -cyano- [5- (E / Z) - ({4- [3- (3-dimethylamino-propyl) -ureido] -phenylamino} -methylene) -3-ethyl-4-oxo-thiazolidine -2-ylidene] acetic acid ethyl ester,

(E or Z) -cyano- [5- (E / Z) - ({3- [3- (3-dimethylamino-propyl) -ureido] -4-fluoro-phenylamino} -methylene) -3-ethyl-4 -oxo-thiazolidin-2-ylidene] -acetic acid ethyl ester, (E or Z) -cyano- {3-ethyl-5- (E / Z) - [(4-fluoro-3- {3- [2- (1- methyl-pyrrolidin-2-yl) ethyl] -urido} -phenylamino) -methylene] -4-oxo-thiazolidin-2-ylidene} - acetic acid ethyl ester,

(E or Z) -Cyano- {3-ethyl-5- (E / Z) - [(4-fluoro-3 - {[4- (2-hydroxy-ethyl) -piperazine-1-carbonyl] -amino} -phenylamino) -methylene] -4-oxo-thiazolidin-2-ylidene} - acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-4-oxo-5- (E / Z) - ({4- [3- (2-pyrrolidin-1-yl-ethyl) -ureido] -phenylamino} - methylene) -thiazolidin-2-ylidene] -acetic acid ethyl ester,

(E or Z) -cyano- [3-ethyl-5- (E / Z) - ({4 - [(4-methylpiperazine-1-carbonyl) -amino] -phenylamino} -methylene) -4-oxo -thiazoIidin-2-ylidene] acetic acid ethyl ester.

9. Uses of the compounds of the general formulas IIA or MB

in which D is the group -NO ₂ , -NH ₂ or -NH (CO) OC (CH ₃ ) ₃ and E is C 1 -C 6 -alkoxy or halogen and R ³ and R ⁴ are as described in general formula I. have, as intermediates for the preparation of the substances of general formula I.

10. Uses of the compounds of the general formulas INA or IIIB

11. Uses of the compounds of the general formulas IVA or IVB

in which D represents the group -NO ₂ , -NH ₂ or -NH (CO) OC (CH ₃ ) ₃ and K represents optionally substituted by the group -NR ³ R ⁴ -substituted dC ₆ -alkyl or dC ₆ -alkenyl and L for optionally mono- or polysubstituted, identically or differently, with C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkoxy-C ₁ -C ₆ -alkoxy or the group -NR ³ R ⁴ -substituted C ₁ -C ₆ -alkyl or C ₁ -C ₆ -alkenyl and R ³ and R ⁴ in the general formula I have described meaning, as intermediates for the preparation of the substances of general formula I.

12. Compounds of the general formula V

^V in which Q, A, B and R ^{1 have} the meaning described in general formula I, as intermediates for the preparation of the compounds of general formula I according to the invention, with the proviso that cyano- [3-ethyl-4-oxo-5- 1-phenylamino-meth- (E / Z) -ylidene] -thiazolidine (2- (E or Z)) - ylidenes] acetic acid does not fall under the general formula V.

13. Use of the compounds of general formula I, according to claims 1 to 5, for the manufacture of a medicament for the treatment of cancer, autoimmune diseases, chemotherapeutic-induced alopecia and mucositis, cardiovascular diseases, infectious diseases, nephrological diseases, chronic and acute neurodegenerative diseases and viral infections.

14. Use according to claim 13, characterized in that under cancer solid tumors and leukemia, autoimmune diseases psoriasis, alopecia and multiple sclerosis, cardiovascular diseases, stenoses, atherosclerosis and restenosis, infectious diseases caused by unicellular parasites diseases, nephrological disorders glomerulonephritis, Chronic neurodegenerative disorders include Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, AIDS dementia and Alzheimer's disease, brain ischemia and neurotrauma in acute neurodegenerative disorders, and viral infections include cytomegalovirus infections, herpes, hepatitis B and C, and HIV are.

15. Medicaments containing at least one compound according to claims 1 to 5.

16. Medicament according to claim 15, for the treatment of cancer, autoimmune diseases, cardiovascular diseases, infectious diseases, nephrological diseases, neurodegenerative diseases and viral infections.

17. Compounds according to claims 1 to 5 or medicaments according to claims 15 or 16 with suitable formulation and excipients.

18. Use of the compounds of general formula I, according to claims 1 to 5, and the medicaments, according to claims 15 or 16 as inhibitors of polo-like kinases.

19. Use according to claim 18, characterized in that the kinase PIkl, Plk2, Plk3 or Plk4.

20. Use of the compounds of general formula I, according to claims 1 to 5, in the form of a pharmaceutical preparation for enteral, parenteral and oral administration.