KR102735378B1 - Novel piperidine-2,6-dione derivatives and use thereof - Google Patents

Abstract

The present invention relates to a novel piperidine-2,6-dione derivative and its use, and more particularly, to a piperidine-2,6-dione derivative compound having an analogue structure of thalidomide. The compound of chemical formula 1 according to the present invention specifically binds to CRBN protein and is involved in its function. Therefore, the compound of the present invention can be usefully used for the prevention or treatment of leprosy, chronic graft-versus-host disease, inflammatory diseases, or cancer caused by the action of CRBN protein.

Description

{Novel piperidine-2,6-dione derivatives and use thereof}

The present invention relates to a novel piperidine-2,6-dione derivative and its use, and more particularly, to a piperidine-2,6-dione derivative compound exhibiting a preventive or therapeutic effect on leprosy, chronic graft-versus-host disease, inflammatory diseases, or cancer.

Thalidomide is a racemic compound sold under the trade name THALOMID (registered trademark) and the chemical name α-(N-phthalimido)glutarimide or 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione. Thalidomide was originally developed to treat morning sickness, but its use was discontinued because of its teratogenic effects. Thalidomide is currently approved in the United States for the treatment of erythema nodosum in leprosy in humans (Korean Patent No. 10-0671366).

Additionally, thalidomide has been reported to be used in patients with leprosy, chronic graft-versus-host disease, rheumatoid arthritis, sarcoidosis, some inflammatory skin diseases, and inflammatory bowel disease, and thalidomide can be combined with other drugs to treat ischemia/reperfusion associated with cardiac and cerebral artery occlusions (U.S. Patent No. 05643915).

More recently, thalidomide has been used to treat certain types of cancer. These include refractory multiple myeloma, brain, melanoma, breast, colon, mesothelioma, and renal cell carcinoma. Thalidomide has additionally been reported to prevent the development of chronic cardiomyopathy induced by doxorubicin in rats. Other reports of the use of thalidomide in the treatment of certain cancers include its use in combination with carboplatin in the treatment of glioblastoma multiforme. Thalidomide has also been reported to be used as an analgesic in the treatment of astrocytomas (Costa, P. T. et al., Blood, 92(Suppl 1, Pt 2), 235b, 1998; Marx, G. M. et al., Proc Am Soc Clin Oncol., 454a, 1999; Singhal, S. et al., N Engl J Med., 341(21), 1565-1571, 1999; Zwart, D., Arzneimittelforschung, 16(12), 1688-1689, 1966).

In addition, thalidomide has been used for various purposes such as prevention or treatment of lupus nephritis, fibromyalgia, schizophrenia, central nervous system diseases, diabetes, and inflammatory diseases, but it was withdrawn from the market in late 1961 due to the fatal side effect of causing birth defects in pregnant women who took it.

Research is actively underway to develop a derivative that retains the various physiological usefulness of thalidomide while resolving the problem of serious side effects.

Korean Patent No. 10-0671366, Pharmaceutical composition and dosage form of thalidomide, registered on January 12, 2007. U.S. Patent No. 05643915, Treatment of ischemia/reperfusion injury with thalidomide alone or in combination with other therapies, registered on July 1, 1997.

Chamberlain, P. P. et al., Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs, Nat Struct Mol Biol., 21(9), 803-809, 2014. Costa, P. T. et al., Thalidomide and pentoxifylline prevent the development of chronic cardiomyopathy provoked by doxorubicin in rats without inhibiting its antitumoral effect, Blood, 92(Suppl 1, Pt 2), 235b, 1998. Marx, G. M. et al., A phase I/II trial of thalidomide as an antiangiogenic agent in the treatment of advanced cancer, Proc Am Soc Clin Oncol., 454a, 1999. Matyskiela, M. E. et al., A novel cereblon modulator recruits GSPT1 to the CRL4(CRBN) ubiquitin ligase, Nature, 535(7611), 252-257, 2016. Singhal, S. et al., Antitumor activity of thalidomide in refractory multiple myeloma, N Engl J Med., 341(21), 1565-1571, 1999. Zwart, D., Clinical observations in the influence of thalidomide in the treatment of a leiomyoma in a dog, Arzneimittelforschung, 16(12), 1688-1689, 1966.

The present inventors have made efforts to develop a novel derivative compound that retains the physiological activity of thalidomide while having no side effects of thalidomide, and in particular, have developed a novel thalidomide derivative based on piperidine-2,6-dione and evaluated its activity, thereby completing the present invention.

Accordingly, an object of the present invention is to provide a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof.

The present invention relates to a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof.

[Chemical Formula 1]

In the above chemical formula 1,

X is nitrogen (N) or carbon (C);

R ₁ is selected from the group consisting of -(CH ₂ ) _n NH ₂ , -(CH ₂ ) _m NH(CO)NHR ₄ , -(CH ₂ ) _m NH(CS)NHR ₄ , and -(CH ₂ ) _m NH(CO)R ₄ ;

R ₂ is hydrogen, deuterium or C ₁ -C ₆ alkyl;

R ₃ is hydrogen, C ₁ -C ₆ alkyl, -CH ₂ OCOR ₅ , -CH ₂ OCOOR ₅ , -CH ₂ OCONR ₆ R ₇ or is selected from the group consisting of;

R ₄ is substituted with one or more substituents selected from the group consisting of hydrogen, halogen, hydroxy, substituted or unsubstituted C ₁ -C ₁₀ alkyl, substituted or unsubstituted C ₄ -C ₁₀ cycloalkyl, substituted or unsubstituted C ₄ -C ₁₀ aryl, substituted or unsubstituted C ₁ -C ₁₀ arylalkyl or C ₄ -C ₁₀ heteroaryl,

At this time, the substituted alkyl, cycloalkyl, aryl or arylalkyl is substituted with one or more substituents selected from the group consisting of hydrogen, halogen, hydroxy, CF ₃ , S-CF ₃ , C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₃ -C ₆ cycloalkyl or C ₄ -C ₁₀ aryl;

R ₅ is substituted with one or more substituents selected from the group consisting of hydrogen, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ heterocycloalkyl or -(CH ₂ CH ₂ O) _n CH ₃ ,

At this time, the substituted alkyl, cycloalkyl or heterocycloalkyl is substituted with one or more substituents selected from the group consisting of hydrogen, hydroxy, amino, acetamino, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;

R ₆ and R ₇ are each independently substituted with one or more substituents selected from the group consisting of hydrogen, hydroxy, amino, acetamino, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkyl or substituted or unsubstituted C ₃ -C ₆ heterocycloalkyl,

At this time, the substituted alkyl, alkoxy, cycloalkyl or heterocycloalkyl is substituted with one or more substituents selected from the group consisting of hydrogen, hydroxy, amino, acetamino, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;

R ₈ is substituted with one or more substituents selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, -(CH ₂ ) _m -imidazole, an amino acid residue or a derivative thereof;

n is an integer from 1 to 5; and

m is an integer from 0 to 5;

The following terms in the present invention have the following meanings unless otherwise indicated. Any term not defined has the meaning understood in the art.

“Halogen” in the present invention means fluorine (F), chlorine (Cl), bromine (Br), and iodine (I).

The term "alkyl" used in the present invention means a straight-chain or branched-chain hydrocarbon group with a single bond. Examples include methyl, ethyl, propyl, n-butyl, isobutyl, tert-butyl, 1-methylpropyl, etc.

The term "alkoxy" used in the present invention means an oxygen group bonded to a straight or branched chain saturated hydrocarbon having a single bond. Examples include methoxy, ethoxy, propoxy, n-butoxy, tert-butoxy, and 1-methylpropoxy.

The term "cycloalkyl" used in the present invention means a saturated hydrocarbon group having a ring-shaped single bond. Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

The term "aryl" used in the present invention means an aromatic substituent having at least one ring having a shared pi electron system, examples of which include phenyl, benzyl, etc.

The term "arylalkyl" used in the present invention means an aryl group substituted with an alkyl group, where aryl and alkyl are as disclosed above.

The above term “heterocycloalkyl” refers to a saturated hydrocarbon group with a ring-shaped single bond containing one or more heteroatoms such as N, O, or S, and includes aziridinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, etc., depending on the number and type of heteroatoms contained in the ring and the number of carbon atoms.

The above term “heteroaryl” refers to an aromatic ring compound containing one or more heteroatoms such as N, O, or S, and includes pyrrolyl, furanyl, pyridinyl, pyrimidinyl, pyranyl, etc. depending on the number and type of heteroatoms contained in the ring and the number of carbon atoms.

In the present invention, the pharmaceutically acceptable salt refers to a salt or complex of chemical formula 1 having desirable biological activity. Examples of such salts include, but are not limited to, acid addition salts formed with inorganic acids (e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, etc.), and acid addition salts formed with acetic acid, oxalic acid, tartaric acid, succinic acid, malic acid, fumaric acid, maleic acid, ascorbic acid, benzoic acid, tannic acid, pamoic acid, alginic acid, polyglutamic acid, naphthalene sulfonic acid, naphthalene disulfonic acid, and poly-galacturonic acid. Salts formed with the same organic acid are included. The compounds may also be administered as pharmaceutically acceptable quaternary salts known to those skilled in the art, particularly chloride, bromide, iodide, -O-alkyl, toluenesulfonate, methylsulfonate, sulfonate, phosphate, or carboxylate (e.g., benzoate, succinate, acetate, glycolate, maleate, malate, fumarate, citrate, tartrate, ascorbate, cinnamoate, mandeloate and diphenylacetate).

The acid addition salt according to the present invention can be prepared by a conventional method, for example, by dissolving the derivative of chemical formula 1 in an organic solvent such as methanol, ethanol, acetone, dichloromethane, acetonitrile, etc., adding an organic acid or inorganic acid, filtering and drying the resulting precipitate, or by distilling the solvent and an excess acid under reduced pressure, drying, and crystallizing in the presence of an organic solvent.

In addition, a pharmaceutically acceptable metal salt can be prepared using a base. An alkali metal or alkaline earth metal salt is obtained, for example, by dissolving a compound in an excess of an alkali metal hydroxide or an alkaline earth metal hydroxide solution, filtering off the undissolved compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare a sodium, potassium or calcium salt as a metal salt. In addition, a corresponding salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

The compound of chemical formula 1 of the present invention may include not only pharmaceutically acceptable salts, but also all salts, hydrates, solvates and prodrugs that can be prepared by conventional methods. In addition, the compound of the present invention may contain one or more asymmetric carbon atoms, and may exist in racemic form and optically active form. All such compounds and diastereomers are included in the scope of the present invention.

Preferably, in the chemical formula 1,

In the above chemical formula 1,

X is nitrogen (N) or carbon (C);

R ₁ is selected from the group consisting of -(CH ₂ ) _n NH ₂ , -(CH ₂ ) _m NH(CO)NHR ₄ , -(CH ₂ ) _m NH(CS)NHR ₄ , and -(CH ₂ ) _m NH(CO)R ₄ ;

R ₂ is hydrogen;

R ₃ is hydrogen, C ₁ -C ₆ alkyl, -CH ₂ OCOR ₅ , -CH ₂ OCOOR ₅ , -CH ₂ OCONR ₆ R ₇ or is selected from the group consisting of;

R ₄ is substituted with one or more substituents selected from the group consisting of hydrogen, halogen, hydroxy, substituted or unsubstituted C ₁ -C ₁₀ alkyl, substituted or unsubstituted C ₄ -C ₁₀ cycloalkyl, substituted or unsubstituted C ₄ -C ₁₀ aryl, substituted or unsubstituted C ₁ -C ₁₀ arylalkyl or C ₄ -C ₁₀ heteroaryl,

At this time, the substituted alkyl, cycloalkyl, aryl or arylalkyl is substituted with one or more substituents selected from the group consisting of hydrogen, halogen, hydroxy, CF ₃ , S-CF ₃ , C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₃ -C ₆ cycloalkyl or C ₄ -C ₁₀ aryl;

R ₅ is substituted with one or more substituents selected from the group consisting of hydrogen, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ heterocycloalkyl or -(CH ₂ CH ₂ O) _n CH ₃ ,

At this time, the substituted alkyl, cycloalkyl or heterocycloalkyl is substituted with one or more substituents selected from the group consisting of hydrogen, hydroxy, amino, acetamino, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;

R ₆ and R ₇ are each independently substituted with one or more substituents selected from the group consisting of hydrogen, hydroxy, amino, acetamino, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkyl or substituted or unsubstituted C ₃ -C ₆ heterocycloalkyl,

At this time, the substituted alkyl, alkoxy, cycloalkyl or heterocycloalkyl is substituted with one or more substituents selected from the group consisting of hydrogen, hydroxy, amino, acetamino, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;

R ₈ is substituted with one or more substituents selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl or -(CH ₂ ) _m -imidazole;

n is an integer from 1 to 3; and

m is an integer from 0 to 3;

More specifically, the compound of the chemical formula 1 of the present invention is exemplified as follows:

1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 1);

1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 2);

1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-5-yl)methyl)urea (Compound 3);

1-(3-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 4);

1-(4-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 5);

1-(3,4-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 6);

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 7);

1-(3-chloro-4-methoxyphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 8);

3-Chloro-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)benzamide (Compound 9);

3-Chloro-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-4-methylbenzamide (Compound 10);

1-(3-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)thiourea (Compound 11);

2-(3-chlorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 12);

tert-Butyl((2R)-1-(((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (Compound 13);

(2R)-2-Amino-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-phenylpropanamide hydrochloride (Compound 14);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methoxyphenyl)urea (Compound 15);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methoxyphenylethyl)urea (Compound 16);

2-(2,4-Dichlorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 17);

2-(4-Bromophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 18);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(m-tolyl)urea (Compound 19);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methylbenzyl)urea (Compound 20);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(3-methoxybenzyl)urea (Compound 21);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(p-tolyl)urea (Compound 22);

1-(4-chlorobenzyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 23);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-urea (Compound 24);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-phenylurea (Compound 25);

2-(3-Bromophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 26);

2-(4-chlorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 27);

2-(4-chloro-2-fluorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-7-yl)methyl)acetamide (Compound 28);

2-(3,4-difluorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 29);

2-(3,5-difluorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 30);

1-(2-Bromo-4,6-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea (Compound 31);

1-(2-Bromo-4,6-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea (Compound 32);

1-(2-chloro-4-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 33);

1-(2,3-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 34);

1-(3-chloro-4-methoxyphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-6-yl)methyl)urea (Compound 35);

1-(4-chlorobenzyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 36);

1-(4-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 37);

1-(2,6-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 38);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(m-tolyl)urea (Compound 39);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-urea (Compound 40);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(p-tolyl)urea (Compound 41);

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 42);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-methoxyphenyl)urea (Compound 43);

1-(3,4-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 44);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(trifluoromethyl)phenyl)urea (Compound 45);

1-(3,5-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 46);

1-(2,6-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 47);

1-(2-Bromo-4,6-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 48);

1-(2-Bromo-4,6-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 49);

1-(2-chloro-4-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 50);

1-(2,3-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 51);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(trifluoromethyl)phenyl)urea (Compound 52);

1-(3,4-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 53);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methoxyphenylethyl)urea (Compound 54);

3-((3-(2,6-deoxypiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)diethylurea (Compound 55);

3-((3-(2,6-deoxypiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)diethylurea (Compound 56);

1-(4-(tert-butyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 57);

1-(4-(tert-butyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 58);

1-(Benzo[d][1,3]dioxol-5-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-7-yl)methyl)urea (Compound 59);

1-(Benzo[d][1,3]dioxol-5-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)methyl)urea (Compound 60);

1-(Benzo[d]thiazol-6-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea (Compound 61);

1-(3-chloro-4-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-6-yl)methyl)urea (Compound 62);

1-(4-Bromo-2-chloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 63);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-fluoro-3-methylphenyl)urea (Compound 64);

1-(3,4-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 65);

1-(2,4-Dichloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea (Compound 66);

1-(2,4-Dichloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea (Compound 67);

1-(4-Bromo-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)methyl)urea (Compound 68);

1-(4-Bromo-3-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 69);

1-(4-Bromo-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 70);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(trifluoromethyl)phenyl)urea (Compound 71);

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 72);

1-(3-chloro-4-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 73);

1-(4-Bromo-2-chloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 74);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-fluoro-3-methylphenyl)urea (Compound 75);

1-(3,4-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 76);

1-(2,4-Dichloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-7-yl)methyl)urea (Compound 77);

1-(3-Bromo-4-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 78);

1-(4-Bromo-3-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 79);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-(trifluoromethyl)phenyl)urea (Compound 80);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-((trifluoromethyl)thio)phenyl)urea (Compound 81);

1-(3,4-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 82);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(3,4,5-trifluorophenyl)urea (Compound 83);

1-(2,4-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 84);

1-(3,4-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 85);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(3,4,5-trifluorophenyl)urea (Compound 86);

1-(2,4-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 87);

1-(4-Bromo-3-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-7-yl)methyl)urea (Compound 88);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(trifluoromethyl)phenyl)urea (Compound 89);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-phenylurea (Compound 90);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-isobutylurea (Compound 91);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-methylcyclohexyl)urea (Compound 92);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-urea (Compound 93);

1-(4-chloro-2-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 94);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-urea (Compound 95);

1-(4-Cyclopropylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 96);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(trifluoromethyl)phenyl)urea (Compound 97);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-isobutylphenyl)urea (Compound 98);

1-([1,1'-Biphenyl]-3-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 99);

1-(3-(tert-butyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 100);

1-([1,1'-Biphenyl]-4-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 101);

1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(5,6,7,8-tetrahydronaphthalen-2-yl)urea (Compound 102);

1-(4-(tert-butyl)-3-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 103);

(2,3-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 104);

1-(3-chloro-4-methylphenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)ethyl)urea (Compound 105);

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 106);

1-(4-(tert-butyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 107);

1-([1,1'-Biphenyl]-3-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)ethyl)urea (Compound 108);

1-(3-(tert-butyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 109);

1-(4-(tert-butyl)-3-chlorophenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 110);

1-(4-(tert-butyl)-3-chlorophenyl)-3-(2-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)propan-2-yl)urea (Compound 111);

1-(4-(tert-butyl)benzyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 112);

1-(4-(tert-butyl)benzyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 113);

1-(3-Bromo-4-(tert-butyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)ethyl)urea (Compound 114);

1-(2-(4-chlorophenyl)propan-2-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)ethyl)urea (Compound 115);

1-(1-(4-chlorophenyl)ethyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 116);

1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(5,6,7,8-tetrahydronaphthalen-2-yl)urea (Compound 117);

1-(2,3-Dihydro-1H-indene-5-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 118);

1-(4-chloro-3-methylphenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)ethyl)urea (Compound 119);

1-(3-(tert-butyl)-4-chlorophenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 120);

1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(3'-methyl-[1,1'-biphenyl]-3-yl)urea (Compound 121);

1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(9H-fluoren-3-yl)urea (Compound 122);

1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(2'-methyl-[1,1'-biphenyl]-3-yl)urea (Compound 123);

1-(3-(Benzo[d]thiazol-2-yl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 124);

1-(4'-Chloro-[1,1'-biphenyl]-3-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 125);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methyl acetate (Compound 126);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylisobutyrate (Compound 127);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylcyclopentanecarboxylate (Compound 128);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methyl prolanate (Compound 129);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methyl methyl carbonate (Compound 130);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methyl methyl carbonate (Compound 131);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylpiperidin-4-ylcarbonate (Compound 132);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2-(2-methoxyethoxy)ethoxy)ethyl)carbonate (Compound 133);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2-acetamidoethyl)carbamate (Compound 134);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2-((R)-2-amino-3-methylbutanamido)ethyl)carbamate (Compound 135);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2,6-dioxopiperidin-1-yl)methyl(2-aminoethyl)carbamate (Compound 136);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2,6-dioxopiperidin-1-yl)methylvalinate (Compound 137);

(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylhistine (Compound 138);

3-(7-(Aminomethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-yl)piperidine-2,6-dione (Compound 139);

3-(6-(Aminomethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-yl)piperidine-2,6-dione (Compound 140);

3-(5-(Aminomethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-yl)piperidine-2,6-dione (Compound 141);

1-(3-chloro-4-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 142);

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 143);

1-(3-chloro-4-methoxyphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 144);

1-(3-chloro-4-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-6-yl)methyl)urea (Compound 145);

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-6-yl)methyl)urea (Compound 146);

1-(3,4-Dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 147);

1-(3,5-Dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 148);

1-(2,3-Dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 149);

1-(2-chloro-4-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 150);

1-(4-Bromo-3-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 151);

1-(4-(tert-butyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 152);

1-(3-chlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 153);

1-(4-chlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 154);

1-(4-Bromo-2-chloro-6-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 155);

1-(4-Bromo-2-chloro-6-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 156);

1-(4-chlorobenzyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 157);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-fluorophenethyl)urea (Compound 158);

1-(2,6-Dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 159);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(m-tolyl)urea (Compound 160);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-fluoro-3-methylphenyl)urea (Compound 161);

1-(3,4-dimethylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 162);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-((trifluoromethyl)thio)phenyl)urea (Compound 163);

1-(Benzo[d][1,3]dioxol-5-ylmethyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 164);

1-(Benzo[d]thiazol-6-yl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 165);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(p-tolyl)urea (Compound 166);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(3,4,5-trifluorophenyl)urea (Compound 167);

1-(4-Bromo-3-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 168);

1-(3-chloro-4-methoxyphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 169);

1-(3-chloro-4-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 170);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-methoxyphenyl)urea (Compound 171);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(3-fluoro-4-(trifluoromethyl)phenyl)urea (Compound 172);

1-(2-Bromo-4,6-difluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 173);

3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-1,1-diethylurea (Compound 174);

1-(2-Bromo-4,6-dimethylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 175);

1-(3-Bromo-4-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 176);

1-(3,4-difluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 177);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-methoxyphenethyl)urea (Compound 178);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-fluorophenyl)urea (Compound 179);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-methylcyclohexyl)urea (Compound 180);

1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-isopropylphenyl)urea (Compound 181);

1-(3,5-Difluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 182);

1-(4-Bromo-2-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 183);

1-(4-chloro-2-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 184);

1-(3-chloro-4-methylphenyl)-3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)ethyl)urea (Compound 185);

1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)ethyl)urea (Compound 186);

1-(3-chloro-4-methoxyphenyl)-3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)ethyl)urea (Compound 187);

3-(6-(aminomethyl)-1-oxoisoquinolin-2(1H)-yl)piperidine-2,6-dione hydrochloride (compound 188); and

3-(7-(aminomethyl)-1-oxoisoquinolin-2(1H)-yl)piperidine-2,6-dione hydrochloride (Compound 189); is selected from the group consisting of:

Most preferably, in the chemical formula 1,

X is nitrogen (N);

R ₁ is selected from the group consisting of -(CH ₂ ) _n NH ₂ , -(CH ₂ ) _m NH(CO)NHR ₄ , -(CH ₂ ) _m NH(CS)NHR ₄ , and -(CH ₂ ) _m NH(CO)R ₄ ;

R ₂ is hydrogen, deuterium or C ₁ -C ₆ alkyl;

R ₃ is hydrogen, C ₁ -C ₆ alkyl, -CH ₂ OCOR ₅ , -CH ₂ OCOOR ₅ , -CH ₂ OCONR ₆ R ₇ or is selected from the group consisting of;

R ₄ is substituted with one or more substituents selected from the group consisting of hydrogen, halogen, hydroxy, C ₁ -C ₁₀ alkyl, substituted or unsubstituted C ₄ -C ₁₀ cycloalkyl, substituted or unsubstituted C ₄ -C ₁₀ aryl, substituted or unsubstituted C ₁ -C ₁₀ arylalkyl or C ₄ -C ₁₀ heteroaryl,

At this time, the substituted alkyl, cycloalkyl, aryl or arylalkyl is substituted with one or more substituents selected from the group consisting of hydrogen, halogen, hydroxy, CF ₃ , S-CF ₃ , C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₃ -C ₆ cycloalkyl or C ₄ -C ₁₀ aryl;

R ₅ is substituted with one or more substituents selected from the group consisting of hydrogen, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ heterocycloalkyl or -(CH ₂ CH ₂ O) _n CH ₃ ,

At this time, the substituted alkyl, cycloalkyl or heterocycloalkyl is substituted with one or more substituents selected from the group consisting of hydrogen, hydroxy, amino, acetamino, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;

R ₆ and R ₇ are each independently substituted with one or more substituents selected from the group consisting of hydrogen, hydroxy, amino, acetamino, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkyl or substituted or unsubstituted C ₃ -C ₆ heterocycloalkyl,

At this time, the substituted alkyl, alkoxy, cycloalkyl or heterocycloalkyl is substituted with one or more substituents selected from the group consisting of hydrogen, hydroxy, amino, acetamino, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;

R ₈ is substituted with one or more substituents selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, -(CH ₂ ) _m -imidazole, an amino acid residue or a derivative thereof;

n is an integer from 1 to 5; and

m is an integer from 0 to 5;

In addition, the compound represented by the chemical formula 1 of the present invention is prepared by the method of the following reaction scheme 1, which is a method disclosed in Korean Patent Application No. 10-2017-0184761.

(a) a step of reacting a compound represented by the following chemical formula 2 with a compound represented by the following chemical formula 3 to produce a compound represented by the following chemical formula 4; and

(b) A method for producing a compound represented by the following chemical formula 5 by reacting a compound represented by the following chemical formula 4 with NaNO ₂ :

[Chemical formula 2]

[Chemical Formula 3]

[Chemical Formula 4]

[Chemical Formula 5]

In the above chemical formula 2, R ₁ is substituted with a substituent selected from the group consisting of -(CH ₂ ) _n NH ₂ , -(CH ₂ ) _m NH(CO)NHR ₄ , -(CH ₂ ) _m NH(CS)NHR ₄ , or -(CH ₂ ) _m NH(CO)R ₄ .

The solvent used in the step (a) of the present invention is not particularly limited as long as it is a solvent that dissolves the starting material and does not inhibit the reaction, and for example, an ether solvent such as tetrahydrofuran, 1,2-dimethoxyethane, diethyl ether or dioxane; an aromatic hydrocarbon solvent such as benzene, toluene or xylene; an amide solvent such as N,N-dimethylformamide, N,N-dimethylacetamide or N-methylpyrrolidone; an organic solvent such as dimethyl sulfoxide; an alcohol solvent such as methanol, ethanol, propanol, n-butanol or t-butanol; or a mixture thereof or a mixed solvent of the above solvents and water can be used. Dimethylformamide can be preferably used, but is not limited thereto.

In addition, in order to facilitate the reaction in step (a), an appropriate base may be used. As the base, for example, sodium hydride, potassium t-butoxide, sodium methoxide, sodium ethoxide, N,N-diisopropylamine, diisopropylethylamine 2,4-diaminobutyric acid (DBU) may be used, and diisopropylethylamine is preferably used, but is not limited thereto.

In the above step (a), the reaction molar ratio of the compound of chemical formula 2 and the compound of chemical formula 3 may be 1:3 to 5, and most preferably, the reaction is carried out at a molar ratio of 1:4.

The above step (b) is a step for performing a cyclization reaction by adding sodium nitride to the compound of chemical formula 4 produced in the above step (a), and it is preferable to perform the reaction under weakly acidic conditions at room temperature.

The method for producing a compound represented by chemical formula 1 according to the present invention shown in the above manufacturing method should be understood as an example of a method for producing a compound of the present invention, and any method capable of producing a compound represented by chemical formula 1 manufactured by the present invention is included in the present invention without limitation. In addition, the method presented in the specification of the present invention and a manufacturing method that can be easily modified and attempted by a person skilled in the art should also be understood to be included in the scope of the present invention, and this can be understood as being obvious to a person skilled in the art.

In addition, the present invention relates to a pharmaceutical composition for preventing or treating leprosy, chronic graft-versus-host disease, inflammatory disease or cancer, comprising a compound represented by the chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

According to one test example of the present invention, it was confirmed that it decomposes Ikaros/Aiolos and GSPT1 by binding to CRBN (celebron) protein. CRBN protein is a type of E3 ubiquitin ligase and is known to have the activity of attaching ubiquitin to substrate proteins such as Ikaros/Aiolos protein and GSPT1 protein by binding to thalidomide and its analogs such as pomalidomide and lenalidomide.

The above cancer may be selected from the group consisting of breast cancer, colon cancer, lung cancer, small cell lung cancer, stomach cancer, liver cancer, blood cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, anal cancer, colon cancer, breast cancer, fallopian tube carcinoma, endometrial carcinoma, cervical cancer, vaginal cancer, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvic carcinoma, CNS tumor, primary CNS lymphoma, spinal cord tumor, brainstem glioma, and pituitary adenoma, but is not particularly limited thereto.

The pharmaceutical composition according to the present invention can be formulated in a suitable form together with a pharmaceutically acceptable carrier that is generally used. "Pharmaceutically acceptable" means a composition that is physiologically acceptable and does not usually cause allergic reactions or similar reactions such as gastrointestinal disorders, dizziness, etc. when administered to humans. In addition, the composition can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injectable solutions, respectively, according to a conventional method.

Carriers, excipients and diluents that may be included in the above composition include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl paraoxybenzoate, propyl paraoxybenzoate, talc, magnesium stearate and mineral oil. When formulated, the composition is prepared using diluents or excipients such as commonly used fillers, stabilizers, binders, disintegrants and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing the compound of the present invention with at least one excipient, such as starch, microcrystalline cellulose, sucrose or lactose, low-substituted hydroxypropyl cellulose, hypromellose, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solutions for oral administration, emulsions, syrups, etc., and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, flavoring agents, preservatives, etc. may be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspending agents can be used, such as propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases can be used, such as witepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerol, gelatin, etc. In order to formulate a dosage form for parenteral administration, the compound of the above chemical formula 1 or a pharmaceutically acceptable salt thereof is sterilized and/or mixed in water together with auxiliary agents such as preservatives, stabilizers, wetting agents or emulsifying promoters, salts for osmotic pressure control, and/or buffers, and other therapeutically useful substances, and the solution or suspension can be prepared, and this can be prepared in a unit dosage form, such as an ampoule or vial.

The above pharmaceutical composition provides a pharmaceutical composition comprising a compound of the above chemical formula 1 and an excipient. The compound may be added in an amount of preferably 0.001 wt% to 50 wt%, more preferably 0.001 wt% to 40 wt%, and most preferably 0.001 wt% to 30 wt% based on the total weight of the entire composition.

The pharmaceutical composition containing the compound of chemical formula 1 disclosed in the present invention as an active ingredient can be administered to mammals such as mice, livestock, and humans by various routes. All modes of administration can be expected, and for example, it can be administered orally, rectally, or by intravenous, intramuscular, subcutaneous, intrauterine, or intracerebrovascular injection. The dosage will vary depending on the age, sex, and weight of the subject to be treated, the specific disease or pathological condition to be treated, the severity of the disease or pathological condition, the time of administration, the route of administration, the absorption, distribution, and excretion rates of the drug, the types of other drugs used, and the judgment of the prescriber. The determination of the dosage based on these factors is within the level of those skilled in the art, and the dosage is generally in the range of 0.01 mg/kg/day to about 2000 mg/kg/day. A more preferred dosage is 1 mg/kg/day to 500 mg/kg/day. The administration can be administered once a day or divided into several times. The above dosage does not limit the scope of the present invention in any way.

The compound of chemical formula 1 according to the present invention specifically binds to CRBN protein and participates in its function. Therefore, the compound of the present invention can be usefully used in the prevention or treatment of leprosy, chronic graft-versus-host disease, inflammatory diseases, or cancer caused by the action of CRBN protein.

Figure 1 shows the results of measuring the decomposition activity for GSPT1 and Aiolos when compounds 1, 2, 110, and 143 of the present invention were treated for 6 hours or 24 hours.

Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, the contents introduced herein are provided to be thorough and complete and to sufficiently convey the idea of the present invention to those skilled in the art.

<Example 1. Synthesis and physical and chemical properties of piperidine-2,6-dione derivative compounds>

Compounds 1 to 189 of the present invention were manufactured with reference to the method disclosed in Korean Patent Application No. 10-2017-0184761, and their physicochemical properties are as follows.

Compound 1. 1-(3- Chloro -4- Methylphenyl )-3-((3-(2,6- Dioxopiperidine -3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.19 (s, 1H), 8.90 ₍ s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.17 (s, 1H), 8.05 (d, J = 8.5 Hz, 1H), 7.65 (s, 1H), 7.20-7.13 (m, 2H), 6.98 (t, J = 6.1 Hz, 1H), 6.01-5.95 (m, 1H), 4.52 (s, 2H), 3.03-2.90 (m, 1H), 2.76 -2.63 (m, 2H), 2.32-2.23 (m, 1H), 2.23 (s, 3H).

Compound 2. 1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.21 (s, 1H), 8.97 (s, 1H), 8.17-8.07 (m, 2H), 7.88 (d, J = 7.1 Hz, 1H), 7.64 ( d, J = 2.1 Hz, 1H), 7.17 (d, J = 8.3 Hz, 1H), 7.09 (dd, J = 8.2, 2.2 Hz, 1H), 6.81 (t, J = 6.3 Hz, 1H), 6.03-5.98 (m, 1H), 4.84 (d, J = 6.1 Hz, 2H), 3.04-2.93 (m, 1H), 2.79-2.65 (m, 2H), 2.34-2.25 (m, 1H), 2.22 (s, 3H).

Compound 3. 1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-5-yl)methyl)urea

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.21 (s, 1H), 8.97 (s, 1H), 8.17-8.07 (m, 2H), 7.88 (d, J = 7.1 Hz, 1H), 7.64 ( d, J = 2.1 Hz, 1H), 7.17 (d, J = 8.3 Hz, 1H), 7.09 (dd, J = 8.2, 2.2 Hz, 1H), 6.81 (t, J = 6.3 Hz, 1H), 6.03-5.98 (m, 1H), 4.84 (d, J = 6.1 Hz, 2H), 3.04-2.93 (m, 1H), 2.79-2.65 (m, 2H), 2.34-2.25 (m, 1H), 2.22 (s, 3H).

Compound 4. 1-(3-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.17 (s, 1H), 9.01 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.11 (s, 1H), 7.91 (dd, J = 8.2, 1.6 Hz, 1H), 7.68 (s, 1H), 7.25-7.23 (m, 2H), 7.02 (t, J = 6.1 Hz, 1H), 6.98-6.93 (m, 1H), 6.01-5.95 (m, 1H), 4.57 (d, J = 6.0 Hz, 2H), 3.03-2.92 (m, 1H), 2.77-2.64 (m, 2H), 2.31-2.24 (m, 1H).

Compound 5. 1-(4-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.18 (s, 1H), 8.93 (s, 1H), 8.25 (d, J = 8.2 Hz, 1H), 8.11 (s, 1H), 7.90 (dd, J = 8.2, 1.6 Hz, 1H), 7.48-7.43 (m, 2H), 7.29-7.24 (m, 2H), 6.97 (t, J = 6.0 Hz, 1H), 6.01-5.95 (m, 1H), 4.57 (d, J = 5.9 Hz, 2H) , 3.03-2.92 (m, 1H), 2.77-2.63 (m, 2H), 2.31-2.24 (m, 1H).

Compound 6. 1-(3,4- Dichlorophenyl )-3-((3-(2,6- Dioxopiperidine -3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.18 (s, 1H), 9.13 ₍ s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.11 (s, 1H), 7.90 (dd, J = 8.2, 1.6 Hz, 1H), 7.85 (d, J = 2.5 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H), 7.30 (dd, J = 8.9, 2.5 Hz, 1H), 7.09 (t, J = 6.1 Hz, 1H), 6.01 -5.95 (m, 1H), 4.57 (d, J = 6.0 Hz, 2H), 3.03-2.91 (m, 1H), 2.77-2.64 (m, 2H), 2.31-2.23 (m, 1H).

Compound 7. 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.17 (s, 1H), 9.34 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.12 (s, 1H), 8.07 (d, J = 2.5 Hz, 1H), 7.91 (dd, J = 8.2, 1.6 Hz, 1H), 7.63 (dd, J = 8.8, 2.5 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.17 (t, J = 6.2 Hz, 1H), 6.01-5.95 ( m, 1H), 4.58 (d, J = 5.9 Hz, 2H), 3.03-2.90 (m, 1H), 2.76-2.63 (m, 2H), 2.31-2.23 (m, 1H).

Compound 8. 1-(3-chloro-4-methoxyphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.17 (s, 1H), 8.78 (s, 1H), 8.25 (d, J = 8.2 Hz, 1H), 8.11 (s, 1H), 7.90 (dd, J = 8.1, 1.6 Hz, 1H), 7.63 (d, J = 2.6 Hz, 1H), 7.23 (dd, J = 8.9, 2.6 Hz, 1H), 7.03 (d, J = 9.0 Hz, 1H), 6.95 (t, J = 6.0 Hz, 1H), 6.01 -5.95 (m, 1H), 4.56 (d, J = 6.0 Hz, 2H), 3.03-2.91 (m, 1H), 2.77-2.63 (m, 2H), 2.32-2.24 (m, 1H).

Compound 9. 3-chloro-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)benzamide

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 9.34 (t, J = 5.9 Hz, 1H), 8.24 (d, J = 8.3 Hz, 1H), 8.18 (s, 1H) , 8.08 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 6.00-5.95 (m, 1H), 4.70 (d, J = 5.9 Hz, 2H) ), 3.01-2.86 (m, 1H), 2.76-2.63 (m, 2H), 2.39 (s, 3H), 2.30-2.23 (m, 1H).

Compound 10. 3-Chloro-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-4-methylbenzamide

^1H NMR (300 MHz, DMSO -d6 ) δ 11.19 (s, 1H), 8.90 ₍ s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.17 (s, 1H), 8.05 (d, J = 8.5 Hz, 1H), 7.65 (s, 1H), 7.20-7.13 (m, 2H), 6.98 (t, J = 6.1 Hz, 1H), 6.01-5.95 (m, 1H), 4.52 (s, 2H), 3.03-2.90 (m, 1H), 2.76 -2.63 (m, 2H), 2.32-2.23 (m, 1H), 2.23 (s, 3H);

LC/MS (ESI) m/z 439.9[M+H] ⁺ , 437.9[MH] ^- .

Compound 11. 1-(3-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)thiourea

^1H NMR (500 MHz, DMSO _-d6 ) δ 11.20 (s, 1H), 10.00 (s, 1H), 8.60 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.12 (s, 1H), 7.92 (dd, J = 8.2, 1.6 Hz, 1H), 7.68 (s, 1H), 7.36 (d, J = 5.1 Hz, 2H), 7.19-7.17 (m, 1H), 6.00-5.97 (m, 1H), 5.01 (d, J = 5.8 Hz) , 2H), 3.00-2.93 (m, 1H), 2.74-2.63 (m, 2H), 2.30-2.27 (m, 1H).

Compound 12. 2-(3-chlorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide

^1H NMR (500 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.85 (t, J = 6.0 Hz, 1H), 8.22 (d, J = 8.1 Hz, 1H), 8.04 (s, 1H) , 7.83 (dd, J = 8.3, 1.3 Hz, 1H), 7.36-7.30 (m, 3H), 7.26 (d, J = 7.4 Hz, 1H), 5.99-5.96 (m, 1H), 4.55 (d, J = 6.0 Hz, 2H), 3.58 (s, 2H) ), 3.00-2.92 (m, 1H), 2.73-2.64 (m, 2H), 2.29-2.25 (m, 1H).

Compound 13. tert-Butyl((2R)-1-(((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.20 (s, 1H), 8.71 (t, J = 5.9 Hz, 0H), 8.18 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H) , 7.76 (d, J = 8.2 Hz, 1H), 7.26 (d, J = 4.3 Hz, 4H), 7.21-7.18 (m, 1H), 7.12 (d, J = 8.2 Hz, 1H), 6.01-5.95 (m, 1H), 4.55-4.52 (m, 2H) , 3.02-2.96 (m, 1H), 2.85-2.76 (m, 1H), 2.73-2.61 (m, 1H), 2.32-2.23 (m, 1H), 1.33 (s, 9H).

Compound 14. (2R)-2-Amino-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-phenylpropanamide hydrochloride

¹ H NMR (300 MHz, DMSO- d ₆ ) δ 11.21 (s, 0.5H), 11.03 (s, 0.5H), 9.86 (d, J = 7.9 Hz, 0.5H), 9.40-9.37 (m, 0.5H) ), 9.18-9.14 (m, 0.5H), 8.96 (s, 0.5H), 8.52 (s, 1.5H), 8.43 (d, J = 8.3 Hz, 0.5H), 8.32 (s, 1.5H), 8.19 (d, J = 8.3 Hz, 0.5H), 8.05 (s, 0.5H), 7.65 (d, J = 8.2 Hz, 0.5H), 7.38-7.21 (m, 5H), 6.02-5.96 (m, 0.5H), 4.94-4.85 (m, 0.5H), 4.59-4.45 (m, 2H), 4.17-4.05 (m, 1H), 3.12-3.02 (m, 2H), 2.86-2.76 (m, 1H), 2.68-2.57 (m, 2H), 2.32-2.21 (m, 2H).

Compound 15. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methoxyphenyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.05 (s, 1H), 8.70 (s, 1H), 8.17 (d, J = 8.6 Hz, 1H), 7.65 (s, 1H), 7.55 (s, 1H), 7.49-7.37 (m, 2H), 7.26-7.18 (m, 1H), 7.04 (d, J = 8.7 Hz, 1H), 6.81 (s, 1H), 6.67 (d, J = 7.0 Hz, 1H), 5.61-5.40 (m, 1H), 4.44 (s, 2H), 3.79 (s, 3H), 2.93-2.78 (m, 1H), 2.76-2.63 (m, 2H), 2.10-1.93 (m, 1H).

Compound 16. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methoxyphenylethyl)urea

^1H NMR (300 MHz, CDCl ₃ ) δ 11.54 (s, 1H), 9.51 (s, 1H), 9.05 (d, J = 8.3 Hz, 1H), 8.58 (d, J = 8.4 Hz, 1H), 8.16 (s, 1H), 8.03 (s, 1H), 7.94 (d, J = 8.7 Hz, 2H), 7.85 (d, J = 7.9 Hz, 1H), 7.67-7.53 (m, 2H), 7.29-7.24 (m, merged with CHCl ₃ , 1H), 6.68 (d , J = 3.5 Hz, 1H), 5.69-5.63 (m, 1H), 4.84 (d, J = 13.5 Hz, 1H), 4.60-4.48 (m, 1H), 3.99 (d, J = 13.5 Hz, 1H), 3.69-3.55 (m, 1H), 3.32-3.21 (m, 1H), 3.21-3.07 ( m, 2H), 3.04-2.81 (m, 5H), 2.70-2.58 (m, 1H), 2.56-2.47 (m, 2H), 2.47-2.36 (m, 3H), 2.18 (s, 3H), 2.06-1.90 (m, 1H) ), 1.88-1.68 (m, 6H), 1.48 (d, J = 7.5 Hz, 3H), 1.40-1.29 (m, 12H), 0.95-0.81 (m, 2H).

Compound 17. 2-(2,4-dichlorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide

^1H NMR (500 MHz, Chloroform- d ) δ 8.78 (d, J = 8.3 Hz, 1H), 8.73 (d, J = 19.9 Hz, 1H), 8.38 (q, J = 5.0 Hz, 1H), 7.73- 7.67 (m, 1H), 7.48-7.40 (m, 4H), 7.35 (d, J = 8.5 Hz, 2H), 6.85 (dd, J = 9.0, 3.4 Hz, 3H), 5.76-5.62 (m, 1H), 4.74-4.63 (m, 1H), 4.14-4.10 (m, 2H), 3.81-3.71 (m, 2H), 3.81-3.71 (m, 7H), 3.52-3.41 (m, 3H), 2.95-2.80 (m, 2H), 2.74-2.67 (m, 3H), 2.43 (s, 3H), 2.36-2.25 (m, 1H) ), 2.09-2.00 (m, 1H), 1.70 (s, 3H).

Compound 18. 2-(4-bromophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide

^1H NMR (500 MHz, Chloroform- d ) δ 8.87 (d, J = 21.3 Hz, 1H), 8.77 (d, J = 11.2 Hz, 1H), 8.36 (q, J = 4.6 Hz, 1H), 7.69 ( t, J = 8.2 Hz, 1H), 7.51-7.39 (m, 4H), 7.35 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 7.7 Hz, 2H), 6.84 (d, J = 9.0 Hz, 3H), 5.69-5.56 (m , 1H), 4.74-4.63 (m, 1H), 4.10 (t, J = 4.8 Hz, 2H), 3.85 (t, 2H), 3.80-3.72 (m, 5H), 3.72-3.64 (m, 10H), 3.55-3.47 (m, 1H), 2.97-2.83 (m, 2H), 2.82-2.66 ( m, 4H), 2.42 (s, 3H), 2.36-2.28 (m, 1H), 1.81 (s, 3H).

Compound 19. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(m-tolyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.19 (s, 1H), 8.71 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.12 (s, 1H), 7.91 (dd, J = 8.2, 1.6 Hz, 1H), 7.27 (s, 1H), 7.23-7.16 (m, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.92 (t, J = 6.0 Hz, 1H), 6.73 (d, J = 7.3 Hz, 1H) , 6.04-5.94 (m, 1H), 4.57 (d, J = 5.8 Hz, 2H), 3.06-2.89 (m, 1H), 2.78-2.57 (m, 2H), 2.35-2.27 (m, 1H), 2.25 (s, 3H).

Compound 20. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methylbenzyl)urea

^1H NMR (300 MHz, Methanol- d ₄ ) δ 8.31-8.22 (m, 2H), 8.08 (s, 1H), 7.83 (dd, J = 8.3, 1.5 Hz, 1H), 7.15 (q, J = 8.1 Hz, 4H), 6.02-5.89 (m, 1H), 4.59 (s, 2H), 4.31 (s, 2H), 3.01-2.76 (m, 3H), 2.44-2.34 (m, 1H), 2.30 (s, 3H).

Compound 21. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(3-methoxybenzyl)urea

^1H NMR (300 MHz, Methanol- d ₄ ) δ 8.28 (d, J = 8.2 Hz, 1H), 8.11 (d, J = 1.6 Hz, 1H), 7.92 (d, J = 0.8 Hz, 1H), 7.86 (d, J = 8.3 Hz, 1H), 7.28-7.18 (m, 1H), 6.93-6.85 (m, 2H), 6.83-6.77 (m, 1H), 6.03-5.93 (m, 1H), 4.62 (s, 2H), 4.35 (s, 2H), 3.78 (d, J = 0.8 Hz, 3H), 3.03-2.78 (m, 3H), 2.45-2.34 (m, 1H).

Compound 22. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(p-tolyl)urea

^1H NMR (300 MHz, Methanol- d ₄ ) δ 8.31 (d, J = 8.2 Hz, 1H), 8.15 (d, J = 1.5 Hz, 1H), 7.91 (dd, J = 8.2, 1.7 Hz, 1H) , 7.31-7.24 (m, 2H), 7.14-7.05 (m, 2H), 6.02-5.91 (m, 1H), 4.66 (s, 2H), 3.03-2.78 (m, 3H), 2.44-2.34 (m, 1H), 2.29 (s, 3H).

Compound 23. 1-(4-chlorobenzyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.21 (s, 1H), 8.25 (d, J = 8.2 Hz, 1H), 8.07 (d, J = 1.6 Hz, 1H), 7.85 (dd, J = 8.2, 1.6 Hz, 1H), 7.44-7.34 (m, 2H), 7.34-7.21 (m, 2H), 6.82 (t, J = 6.1 Hz, 1H), 6.74 (t, J = 6.0 Hz, 1H), 6.08-5.92 (m, 1H), 4.51 ( d, J = 4.6 Hz, 2H), 4.24 (d, J = 4.5 Hz, 2H), 3.07-2.89 (m, 1H), 2.83-2.63 (m, 3H), 2.36-2.24 (m, 1H).

Compound 24. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-urea

^1H NMR (300 MHz, Methanol- d ₄ ) δ 8.26 (d, J = 8.2 Hz, 1H), 8.06 (d, J = 1.6 Hz, 1H), 7.81 (dd, J = 8.2, 1.6 Hz, 1H) , 7.28-7.20 (m, 2H), 7.05-6.96 (m, 2H), 6.02-5.91 (m, 1H), 4.56 (s, 2H), 3.42-3.37 (m, 2H), 3.01-2.84 (m, 3H), 2.80 (t, J = 7.1 Hz, 2H), 2.44-2.36 (m, 1H).

Compound 25. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-phenylurea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.19 (s, 1H), 8.78 ₍ s, 1H), 8.27 (d, J = 8.1 Hz, 1H), 8.13 (s, 1H), 7.92 (d, J = 8.2 Hz, 1H), 7.43 (d, J = 8.1 Hz, 2H), 7.23 (t, J = 7.7 Hz, 2H), 6.96-6.86 (m, 2H), 6.09-5.84 (m, 1H), 4.58 (d, J = 5.9 Hz, 2H), 3.15- 2.86 (m, 1H), 2.74-2.61 (m, 2H), 2.34-2.14 (m, H).

Compound 26. 2-(3-bromophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide

^1H NMR (300 MHz, Methanol- d ₄ ) δ 8.26 (d, J = 8.0 Hz, 1H), 8.05 (s, 1H), 7.80 (dd, J = 8.2, 1.6 Hz, 1H), 7.52 (t, J = 1.8 Hz, 1H), 7.43 (dt, J = 7.7, 1.7 Hz, 1H), 7.38-7.21 (m, 3H), 6.04-5.91 (m, 1H), 4.64 (s, 2H), 3.63 (s, 2H) 3.05-2.77 (m, 3H), 2.44- 2.32 (m, 1H).

Compound 27. 2-(4-chlorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide

^1H NMR (300 MHz, DMSO -d6 ) δ 11.21 (d, J = 7.6 Hz, 1H), 8.83 ₍ s, 1H), 8.23 (t, J = 8.5 Hz, 1H), 8.09-8.01 (m, 1H), 7.88-7.77 (m, 1H), 7.44-7.22 (m, 4H), 6.05-5.90 (m, 1H), 4.61-4.44 (m, 2H), 3.58-3.55 (m, 2H) 3.05-2.86 (m, 1H), 2.81-2.60 (m, 2H), 2.36-2.21 (m, 1H).

Compound 28. 2-(4-chloro-2-fluorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-7-yl)methyl)acetamide

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.21 (s, 1H), 8.91-8.77 (m, 1H), 8.25 (d, J = 8.1 Hz, 1H), 8.08 (s, 0H), 7.85 ( dd, J = 8.3, 1.6 Hz, 1H), 7.45-7.35 (m, 2H), 7.26 (dd, J = 8.2, 2.1 Hz, 1H), 6.06-5.90 (m, 1H), 4.56 (d, J = 5.9 Hz, 2H), 3.64 (s, 2H) 3.09-2.92 (m, 1H), 2.80-2.61 (m, 2H), 2.37-2.20 (m, 1H).

Compound 29. 2-(3,4-difluorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.20 (s, 1H), 8.82 (t, J = 5.9 Hz, 1H), 8.23 (d, J = 8.1 Hz, 1H), 8.03 (s, 0H) , 7.45-7.24 (m, 2H), 7.21-7.09 (m, 1H), 6.07-5.91 (m, 1H), 4.55 (d, J = 5.9 Hz, 2H), 3.58 (s, 2H) 3.06-2.89 (m, 1H), 2.77-2.60 (m , 2H), 2.35-2.20 (m, 1H).

Compound 30. 2-(3,5-difluorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.21 (s, 1H), 8.89 (s, 1H), 8.24 (d, J = 8.2 Hz, 1H), 8.05 (d, J = 1.6 Hz, 1H) , 7.84 (dd, J = 8.1, 1.7 Hz, 1H), 7.19-6.94 (m, 3H), 6.06-5.88 (m, 1H), 4.56 (d, J = 6.0 Hz, 2H), 3.63 (s, 2H) 3.07-2.89 (m, 1H), 2.79- 2.61 (m, 2H), 2.37-2.16 (m, 1H).

Compound 31. 1-(2-bromo-4,6-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea

¹ H NMR (300 MHz, DMSO- d ₆ ) δ 11.21 (s, 0.5H), 11.03 (s, 0.5H), 9.86 (d, J = 7.9 Hz, 0.5H), 9.40-9.37 (m, 0.5H) ), 9.18-9.14 (m, 0.5H), 8.96 (s, 0.5H), 8.52 (s, 1.5H), 8.43 (d, J = 8.3 Hz, 0.5H), 8.32 (s, 1.5H), 8.19 (d, J = 8.3 Hz, 0.5H), 8.05 (s, 0.5H), 7.65 (d, J = 8.2 Hz, 0.5H), 7.38-7.21 (m, 5H), 6.02-5.96 (m, 0.5H), 4.94-4.85 (m, 0.5H), 4.59-4.45 (m, 2H), 4.17-4.05 (m, 1H), 3.12-3.02 (m, 2H), 2.86-2.76 (m, 1H), 2.68-2.57 (m, 2H), 2.32-2.21 (m, 2H).

Compound 32. 1-(2-bromo-4,6-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO - _d6 ) δ 11.21 (s, 1H), 8.34-8.18 (m, 2H), 8.04 (dd, J = 8.3, 1.9 Hz, 1H), 7.93 (s, 1H), 7.31 (s, 1H), 7.06 (s, 1H), 6.97 (s, 1H), 6.15-5.94 (m, 1H), 4.51 (d, J = 6.0 Hz, 2H), 3.11-2.90 (m, 1H), 2.85-2.61 (m, 2H), 2.35 -2.28 (m, 1H), 2.26 (s, 3H), 2.20 (s, 3H).

Compound 33. 1-(2-chloro-4-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.61 (s, 1H), 8.43 (d, J = 8.8 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H) , 8.20 (d, J = 1.4 Hz, 1H), 8.08 (dd, J = 8.4, 2.0 Hz, 1H), 7.94 (t, J = 5.9 Hz, 1H), 7.83 (d, J = 1.6 Hz, 1H), 7.66-7.58 (m, 1H), 6.04-5.94 (m, 1H), 4.61 (d, J = 5.7 Hz, 2H), 3.05-2.88 (m, 1H), 2.78-2.63 (m, 2H), 2.34-2.23 (m, 1H).

Compound 34. 1-(2,3-dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 8.47 (s, 1H), 8.25 (d, J = 8.3 Hz, 1H), 8.19 (d, J = 1.6 Hz, 1H) , 8.14-8.05 (m, 2H), 7.81 (t, J = 5.9 Hz, 1H), 7.31-7.20 (m, 2H), 6.04-5.95 (m, 1H), 4.59 (d, J = 5.9 Hz, 2H), 3.04-2.90 (m, 1H), 2.74-2.62 (m, 2H), 2.33-2.22 (m, 1H).

Compound 35. 1-(3-chloro-4-methoxyphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.19 (s, 1H), 8.76 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.17s (d, J = 1.5 Hz, 1H) ), 8.05 (dd, J = 8.1, 2.1 Hz, 1H), 7.62 (d, J = 2.4 Hz, 1H), 7.22 (dd, J = 9.0, 2.7 Hz, 1H), 7.03 (d, J = 9.0 Hz, 1H), 6.93 (t, J = 6.0 Hz, 1H), 6.02-5.96 (m, 1H), 4.52 (d, J = 6.0 Hz 2H), 3.78 (s, 3H), 3.04-2.91 (m, 1H), 2.77-2.64 (m, 2H), 2.31-2.24 (m, 1H).

Compound 36. 1-(4-chlorobenzyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.2 (s, 1H), 9.40 (s, 1H) 8.24 (d, J = 8.4 Hz, 1H), 8.17 (s, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 7.8 Hz, 2H), 7.25 (t, J = 6.0 Hz, 1H), 7.09 (t, J = 1.8 Hz, 1H), 6.03-5.04 (m, 1H), 4.54 (d, J = 2.7 Hz, 2H), 3.04-2.89 (m, 1H), 2.75-2.61 (m, 2H), 2.33-2.22 (m, 1H).

Compound 37. 1-(4-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.2 (s, 1H), 8.95 (s, 1H) 8.21 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 1.8 Hz, 1H), 8.04 (dd, J = 8.4, 2.1 Hz, 1H), 7.43 (d, J = 9.3 Hz, 2H), 7.24 (d, J = 9.3 Hz, 2H), 6.99 (t, J = 6.0 Hz, 1H), 2.52 (t, J = 6.0 Hz, 1H), 3.83- 2.09 (m, 1H), 2.74-2.57 (m, 2H), 2.33-2.12 (m, 1H).

Compound 38. 1-(2,6-dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.1 (s, 1H), 8.37 (s, 1H) 8.02 (d, J = 9.0 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 7.16-7.10 (m, 1H), 6.07-5.93 (m, 1H), 6.03-5.04 (m, 1H), 4.52 (d, J = 6.0 Hz, 2H), 3.04-2.89 (m, 1H), 2.74-2.64 (m, 2H), 2.33-2.22 (m, 1H).

Compound 39. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(m-tolyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.2 (s, 1H), 9.69 (s, 1H) 8.24 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 1.8 Hz, 1H), 8.05 (dd, J = 8.4, 1.8 Hz, 1H), 7.25 (s, 1H), 7.18 (t, J = 8.4 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 6.90 (t, J = 6.3 Hz, 1H), 6.70 (d, J = 7.5 Hz, 1H), 6.03-5.92 (m, 1H), 4.53 (d, J = 6.0 Hz, 1H) 2.99-2.88 (m, 1H), 2.75-2.65 (m, 2H), 2.32-2.25 (m, 1H), 2.23 (s, 1H).

Compound 40. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.1 (s, 1H), 8.21 (d, J = 8.4 Hz, 1H) _, 8.11 (s, 1H), 8.69 (dd, J = 8.4, 1.8 Hz, 1H), 7.27-7.28 (m, 2H), 7.09 (t, J = 8.7 Hz, 1H), 7.66 (t, J = 8.7 Hz, 1H), 7.14 (t, J = 5.7 Hz, 1H), 6.02-5.09 (m, 1H), 4.44 (d, J = 6.0 Hz, 2H), 3.28-3.16 (m, 2H), 3.04-2.85 (m, 1H), 2.80-2.60 (m, 4H), 2.33-2.22 (m, 1H).

Compound 41. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(p-tolyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.2 (s, 1H), 8.63 (s, 1H) 8.24 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 2.1 Hz, 1H), 8.05 (dd, J = 8.4, 1.8 Hz, 1H), 7.29 (d, J = 7.8 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 6.84 (t, J = 6.0 Hz, 1H), 6.05-5.93 (m, 1H), 4.53 (d, J = 6.0 Hz, 2H), 3.05-2.85 (m, 1H), 2.75-2.59 (m, 2H), 2.31-2.24 (m, 1H), 2.21 (s, 3H).

Compound 42. 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (500 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 9.32 (s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.18 (d, J = 1.4 Hz, 1H) , 8.07-8.05 (m, 2H), 7.62 (dd, J = 8.7, 2.6 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.15 (t, J = 6.0 Hz, 1H), 6.00-5.96 (m, 1H), 4.55 (d, J = 6.0 Hz, 2H), 3.00-2.93 (m, 1H), 2.74-2.63 (m, 2H), 2.29-2.25 (m, 1H).

Compound 43. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-methoxyphenyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 8.56 (s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.17 (d, J = 1.5 Hz, 1H) , 8.05 (dd, J = 8.4, 1.9 Hz, 1H), 7.33-7.28 (m, 2H), 6.83-6.79 (m, 3H), 6.01-5.95 (m, 1H), 4.52 (d, J = 6.0 Hz, 2H), 3.69 (s, 3H), 3.03 -2.90 (m, 1H), 2.77-2.62 (m, 2H), 2.31-2.23 (m, 1H).

Compound 44. 1-(3,4-dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 9.17 (s, 1H), 8.33 (d, J = 3.5 Hz, 1H), 8.24 (d, J = 8.3 Hz, 1H) , 8.18 (dt, J = 5.1, 3.1 Hz, 3H), 8.06 (dd, J = 8.3, 1.9 Hz, 1H), 7.85 (d, J = 2.5 Hz, 1H), 7.47 (d, J = 8.9 Hz, 1H), 7.30 (dd, J = 8.8, 2.5 Hz, 1H), 7.10 (t, J = 6.9 Hz, 1H), 6.10-5.93 (m, 2H), 4.55 (d, J = 5.9 Hz, 2H), 3.03-2.91 (m, 1H), 2.77-2.61 (m, 2H), 2.33-2.21 (m, 1H).

Compound 45. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(trifluoromethyl)phenyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.21 (s, 1H), 9.20 ( _s , 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.22-8.13 (m, 2H), 8.07 ( dd, J = 8.4, 1.5 Hz 1H), 8.02-7.92 (m, 1H), 7.69-7.54 (m, 2H), 7.39 (t, J = 9.7 Hz, 1H), 7.16-7.02 (m, 1H), 6.10-5.91 (m, 1H), 4.56 ( d, J = 5.9 Hz, 2H), 3.08-2.86 (m, 1H), 2.79-2.61 (m, 2H), 2.41-2.21 (m, 1H).

Compound 46. 1-(3,5-dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.19 (s, 1H), 9.27 ₍ s, 1H), 8.26 (d, J = 8.1 Hz, 1H), 8.12 (s, 1H), 7.90 (d, J = 8.6 Hz, 1H), 7.51 (d, J = 1.9 Hz, 2H), 7.22 (t, J = 5.9 Hz, 1H), 7.10 (t, J = 1.9 Hz, 1H), 5.99 (dd, J = 12.3, 5.4 Hz, 1H), 4.57 (d, J = 5.9 Hz, 2H), 3.07-2.88 (m, 1H), 2.76-2.60 (m, 2H), 2.35-2.21 (m, 1H).

Compound 47. 1-(2,6-dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.21 (s, 1H), 8.38 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.15 (s, 1H), 7.90 (dd, J = 8.3, 1.3 Hz, 1H), 7.52 (d, J = 8.1 Hz, 2H), 7.34-7.25 (m, 1H), 7.15 (t, J = 6.2 Hz, 1H), 6.04-5.93 (m, 1H), 4.56 (d, J = 6.0 Hz, 2H), 3.02-2.88 (m, 1H), 2.78-2.61 (m, 2H), 2.33-2.25 (m, 1H).

Compound 48. 1-(2-bromo-4,6-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.20 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.19 (s, 1H), 8.12 (s, 1H), 7.89 (dd, J = 8.2, 1.3 Hz, 1H), 7.58-7.51 (m, 1H), 7.46-7.36 (m, 1H), 7.20 (t, J = 6.1 Hz, 1H), 6.05-5.92 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H) , 3.07-2.88 (m, 1H), 2.8-2.60 (m, 2H), 2.36-2.21 (m, 1H).

Compound 49. 1-(2-bromo-4,6-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.21 (s, 1H), 8.25 (d, J = 8.2 Hz, 1H), 8.14 (s, 1H), 7.95 (s, 1H), 7.90 (dd, J = 8.2, 1.3 Hz, 1H), 7.33 (s, 1H), 7.07 (s, 1H), 7.04-6.92 (m, 1H), 6.04-5.92 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H), 3.06-2.90 (m, 1H) ), 2.78-2.64 (m, 2H), 2.35-2.27 (m, 1H), 2.27 (s, 3H), 2.21 (s, 3H).

Compound 50. 1-(2-chloro-4-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 8.65 (s, 1H), 8.44 (d, J = 8.8 Hz, 1H), 8.35-8.23 (m, 1H), 8.16 ( s, 1H), 7.99 (s, 1H), 7.84 (d, J = 2.1 Hz, 1H), 7.63 (dd, J = 9.0, 2.2 Hz, 1H), 6.05-5.91 (m, 1H), 4.64 (s, 2H), 3.08-2.86 (m, 1H) , 2.84-2.61 (m, 2H), 2.35-2.23 (m, 1H).

Compound 51. 1-(2,3-dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.19 (s, 1H), 8.47 (s, 1H), 8.28 (d, J = 8.2 Hz, 1H), 8.15 (s, 1H), 8.13 (d, J = 2.1 Hz, 1H), 7.92 (dd, 2H), 7.83 (d, J = 5.8 Hz, 1H), 4.63 (d, J = 5.8 Hz, 2H), 3.08-2.88 (m, 1H), 2.78-2.63 (m, 2H), 2.33-2.23 (m , 1H).

Compound 52. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(trifluoromethyl)phenyl)urea

^1H NMR (300 MHz, DMSO- d6 ) δ 11.20 (s, 1H), 9.22 (d, J = 5.0 Hz, 1H) _, 8.26 (d, J = 8.2 Hz, 1H), 8.13 (d, J = 1.5 Hz, 1H), 7.98 (dd, J = 6.5, 2.7 Hz, 1H), 7.96-7.87 (m, 1H), 7.70-7.54 (m, 1H), 7.45-7.29 (m, 1H), 7.19-7.02 (m, 1H), 6.05-5.92 (m, 1H) , 4.58 (d, J = 6.0 Hz, 2H), 3.06-2.89 (m, 1H), 2.79-2.61 (m, 2H), 2.34-2.21 (m, 1H).

Compound 53. 1-(3,4-dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 9.18 ₍ s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.12 (s, 1H), 7.91 (dd, J = 8.1, 1.4 Hz, 1H), 7.86 (d, J = 2.5 Hz, 1H), 7.47 (d, J = 8.8 Hz, 1H), 7.31 (dd, J = 8.8, 2.5 Hz, 1H), 7.11 (t, J = 6.1 Hz, 1H), 6.08 -5.93 (m, 1H), 4.58 (d, J = 5.9 Hz, 2H), 3.04-2.86 (m, 1H), 2.81-2.59 (m, 2H), 2.33-2.19 (m, 1H).

Compound 54. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methoxyphenylethyl)urea

¹ H NMR (300 MHz, CD ₃ OD) δ 8.22 (d, J = 1.5 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.94 (dd, J = 8.4, 2.1 Hz, 1H), 7.13 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz, 2H), 6.00-5.93 (m, 1H), 4.52 (s, 2H), 3.75 (s, 3H), 3.38-3.33 (m, 2H), 2.99-2.80 (m, 3H), 2.72 (t, J = 6.9 Hz, 2H), 2.41-2.35 (m, 1H).

Compound 55. 3-((3-(2,6-deoxypiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)diethylurea

¹ H NMR (300 MHz, CD ₃ OD) δ 8.27 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 0.6 Hz, 1H), 7.86 (dd, J = 8.1, 1.8 Hz, 1H), 6.00-5.93 (m, 1H), 4.62 (s, 2H), 3.41 (s, 2H), 3.34-3.32 (m, 2H), 3.00-2.81 (m, 3H), 2.42-2.36 (m, 1H), 1.19 (t, J = 7.2 Hz, 6H);

LC/MS (ESI) m/z 387.1 [M+H] ⁺ , 385 [MH] ^- .

Compound 56. 3-((3-(2,6-deoxypiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)diethylurea

LC/MS (ESI) m/z 387.1 [M+H] ⁺ , 385 [MH] ^- .

Compound 57. 1-(4-(tert-butyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 9.07 (s, 1H) _, 8.20 (d, J = 15.9 Hz, 1H), 8.04 (d, J = 1.9 Hz, 1H) , 7.77-7.55 (m, 1H), 7.37-7.25 (m, 1H), 7.14-7.01 (m, 2H), 6.04-5.94 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H), 3.05-2.89 (m, 1H), 2.77- 2.61 (m, 2H), 2.39-2.23 (m, 1H).

Compound 58. 1-(4-( tert -butyl)phenyl)-3-((3-(2,6- Dioxopiperidine -3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 9.22 ₍ s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.17 (s, 1H), 8.05 (d, J = 8.5 Hz, 1H), 7.37-7.30 (m, 2H), 7.21-7.13 (m, 1H), 6.04-5.93 (m, 1H), 4.54 (d, J = 5.8 Hz, 2H), 3.06-2.90 (m, 1H), 2.79-2.63 (m , 2H), 2.35-2.22 (m, 1H).

Compound 59. 1-(Benzo[d][1,3]dioxol-5-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.21 (s, 1H), 8.39 (s, 1H), 8.26 (d, J = 8.3 Hz, 1H), 8.19 (s, 1H), 8.15 (d, J = 9.0 Hz, 1H), 8.11-8.04 (m, 1H), 7.76 (d, J = 5.9 Hz, 1H), 7.58 (d, J = 2.5 Hz, 1H), 7.38-7.29 (m, 1H), 6.08-5.95 (m, 1H), 4.59 ( d, J = 5.8 Hz, 2H), 3.09-2.90 (m, 1H), 2.82-2.61 (m, 2H), 2.35-2.22 (m, 1H).

Compound 60. 1-(benzo[d][1,3]dioxol-5-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.18 (s, 1H), 9.04 ( _s , 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.11 (s, 1H), 7.94-7.88 ( m, 1H), 7.71-7.55 (m, 1H), 7.37-7.19 (m, 1H), 7.14-6.95 (m, 1H), 6.05-5.88 (m, 1H), 4.57 (d, J = 6.0 Hz, 2H), 3.07-2.83 (m, 1H) , 2.79-2.62 (m, 2H), 2.37-2.18 (m, 1H).

Compound 61. 1-(benzo[d]thiazol-6-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.17 (s, 1H), 9.22 ₍ s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.11 (s, 1H), 7.90 (d, J = 7.5 Hz, 1H), 7.45-7.28 (m, 2H), 7.18 (t, J = 6.0 Hz, 1H), 6.06-5.86 (m, 1H), 4.57 (d, J = 5.9 Hz, 2H), 3.10-2.87 (m, 1H), 2.79- 2.62 (m, 2H), 2.36-2.19 (m, 1H).

Compound 62. 1-(3- Chloro -4- Fluorophenyl )-3-((3-(2,6- Dioxopiperidine -3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.18 (s, 1H), 9.03 (s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.21-8.14 (m, 1H), 8.11- 8.01 (m, 1H), 7.82-7.72 (m, 1H), 7.32-7.23 (m, 2H), 7.05 (t, J = 6.2 Hz, 1H), 6.01-5.95 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H), 3.06- 2.88 (m, 1H), 2.78-2.58 (m, 2H), 2.33-2.23 (m, 1H).

Compound 63. 1-(4-bromo-2-chloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.20 (s, 1H), 8.28-8.18 (m, 2H), 8.11 (s, 1H), 8.03 (dd, J = 8.4, 1.9 Hz, 1H), 7.59 (d, J = 2.2 Hz, 1H), 7.47 (d, J = 2.1 Hz, 1H), 7.08 (t, J = 6.1 Hz, 1H), 6.01-5.98 (m, 1H), 4.52 (d, J = 6.0 Hz, 2H), 3.07-2.90 (m , 1H), 2.79-2.62 (m, 2H), 2.37-2.26 (m, 1H), 2.23 (s, 3H).

Compound 64. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-fluoro-3-methylphenyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.71 (s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 1.5 Hz, 1H) , 8.06 (dd, J = 8.3, 1.8 Hz, 1H), 7.32 (dd, J = 7.2, 2.5 Hz, 1H), 7.24-7.16 (m, 1H), 6.99 (t, J = 9.2 Hz, 1H), 6.88 (t, J = 5.8 Hz, 1H), 6.05-5.93 (m, 1H), 4.53 (d, J = 6.1 Hz, 2H), 3.08-2.86 (m, 1H), 2.79-2.61 (m, 2H), 2.37-2.21 (m, 1H), 2.18 (d, J = 1.9 Hz, 3H).

Compound 65. 1-(3,4-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.20 (s, 1H), 8.57 (s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.18 (s, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.19 (s, 1H), 7.12 (d, J = 8.2 Hz, 1H), 6.97 (d, J = 8.2 Hz, 1H), 6.85 (t, J = 6.2 Hz, 1H), 6.05-5.94 (m, 1H), 4.53 ( d, J = 5.9 Hz, 2H), 3.08-2.88 (m, 1H), 2.80-2.64 (m, 2H), 2.35-2.24 (m, 1H), 2.16 (s, 3H), 2.13 (s, 3H).

Compound 66. 1-(2,4-dichloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.26-8.18 (m, 2H), 8.12 (s, 1H), 8.03 (d, J = 8.7 Hz, 1H), 7.49 ( s, 1H), 7.35 (s, 1H), 7.12-7.04 (m, 1H), 6.07-5.96 (m, 1H), 4.52 (d, J = 5.9 Hz, 2H), 3.07-2.91 (m, 1H), 2.81-2.61 (m, 2H), 2.37- 2.26 (m, 1H), 2.23 (s, 3H).

Compound 67. 1-(2,4-dichloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.20 (s, 1H), 9.03 (d, J = 5.9 Hz, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.18 (s, 1H) , 8.06 (d, J = 8.5 Hz, 1H), 7.89 (dd, J = 6.2, 2.2 Hz, 1H), 7.38-7.18 (m, 2H), 7.13-7.00 (m, 1H), 6.05-5.92 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H), 3.06-2.89 (m, 1H), 2.79-2.64 (m, 2H), 2.33-2.21 (m, 1H).

Compound 68. 1-(4-bromo-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.20 (s, 1H), 9.32 (s, 1H), 8.24 (d, J = 8.3 Hz, 1H), 8.19 (s, 1H), 8.07 (s, 2H), 7.71 (d, J = 8.8 Hz, 1H), 7.57-7.56 (m, 2H), 7.14 (t, J = 6.1 Hz, 1H), 6.07-5.91 (m, 1H), 4.55 (d, J = 5.9 Hz, 2H), 3.08-2.88 (m , 1H), 2.81-2.61 (m, 2H), 2.36-2.21 (m, 1H).

Compound 69. 1-(4-bromo-3-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.19 (s, 1H), 9.17 ₍ s, 1H), 8.24 (d, J = 8.3 Hz, 1H), 8.17 (d, J = 1.8 Hz, 1H) , 8.05 (dd, J = 8.4, 1.9 Hz, 1H), 7.61 (dd, J = 11.9, 2.4 Hz, 1H), 7.51 (t, J = 8.5 Hz, 1H), 7.12-7.03 (m, 2H), 6.03-5.94 (m, 1H), 4.54 (d) , J = 6.0 Hz, 2H), 3.00-2.89 (m, 1H), 2.75-2.62 (m, 2H), 2.32-2.22 (m, 1H);

LC/MS (ESI) m/z 504.7[M+H] ⁺ , 502.7[MH] ^- .

Compound 70. 1-(4-bromo-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 9.35 ₍ s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.13 (s, 1H), 8.08 (d, J = 2.6 Hz, 1H), 7.91 (dd, 1H), 7.72 (d, J = 8.7 Hz, 1H), 7.56 (dd, J = 8.8, 2.6 Hz, 1H), 7.16 (t, J = 6.0 Hz, 1H), 5.99 (dd, J = 12.3, 5.4 Hz, 1H), 4.59 (d, J = 5.9 Hz, 2H), 3.07-2.88 (m, 1H), 2.78-2.59 (m, 2H), 2.35-2.22 (m, 1H).

Compound 71. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(trifluoromethyl)phenyl)urea

^1H NMR (300 MHz, DMSO- d6 ) δ 11.20 (s, 1H), 9.22 (d, J = 5.0 Hz, 1H) _, 8.26 (d, J = 8.2 Hz, 1H), 8.13 (d, J = 1.5 Hz, 1H), 7.98 (dd, J = 6.5, 2.7 Hz, 1H), 7.96-7.87 (m, 1H), 7.70-7.54 (m, 1H), 7.45-7.29 (m, 1H), 7.19-7.02 (m, 1H), 6.05-5.92 (m, 1H) , 4.58 (d, J = 6.0 Hz, 2H), 3.06-2.89 (m, 1H), 2.79-2.61 (m, 2H), 2.34-2.21 (m, 1H).

Compound 72. 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 9.36 (s, 1H), 8.25 (t, J = 8.6 Hz, 1H), 8.16-8.01 (m, 1H), 7.96- 7.81 (m, 2H), 7.69-7.52 (m, 1H), 7.27-7.12 (m, 1H), 7.07 (t, J = 5.9 Hz, 1H), 6.02-5.95 (m, 1H), 4.60-4.47 (m, 2H), 3.07-2.90 (m , 1H), 2.79-2.63 (m, 2H), 2.34-2.22 (m, 1H).

Compound 73. 1-(3-chloro-4-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 9.04 ₍ s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.12 (s, 1H), 7.91 (d, J = 8.5 Hz, 1H), 7.83-7.73 (m, 1H), 7.28 (dd, J = 6.2, 1.9 Hz, 2H), 7.06 (t, J = 5.9 Hz, 1H), 6.09-5.90 (m, 1H), 4.57 (d, J = 5.9 Hz, 2H), 3.07-2.88 (m, 1H), 2.80-2.61 (m, 2H), 2.35-2.21 (m, 1H).

Compound 74. 1-(4-bromo-2-chloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.12 (s, 2H), 7.89 (d, J = 8.4 Hz, 1H) , 7.60 (d, J = 2.3 Hz, 1H), 7.48 (d, J = 2.3 Hz, 1H), 7.10 (t, J = 6.0 Hz, 1H), 6.07-5.89 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H), 3.08-2.89 (m , 1H), 2.80-2.64 (m, 2H), 2.36-2.26 (m, 1H), 2.23 (s, 3H).

Compound 75. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-fluoro-3-methylphenyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.20 (s, 1H), 8.74 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.11 (s, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.33 (dd, J = 6.9, 2.7 Hz, 1H), 7.26-7.17 (m, 1H), 7.01 (d, J = 9.3 Hz, 1H), 6.99-6.87 (m, 1H), 6.06-5.92 (m, 1H), 4.56 (d) , J = 6.0 Hz, 2H), 3.0-2.90 (m, 1H), 2.80-2.62 (m, 2H), 2.35-2.24 (m, 1H), 2.22-2.13 (m, 3H).

Compound 76. 1-(3,4-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 8.58 ₍ s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.11 (s, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.20 (s, 1H), 7.18-7.09 (m, 2H), 6.98 (d, J = 8.1 Hz, 1H), 6.86 (t, J = 6.0 Hz, 1H), 6.06-5.95 (m, 1H), 4.56 (d, J = 6.0 Hz, 2H), 3.07-2.87 (m, 1H), 2.82-2.61 (m, 2H), 2.36-2.25 (m, 1H), 2.16 (s, 3H), 2.13 (s, 3H).

Compound 77. 1-(2,4-dichloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 8.26 (d, J = 8.2 Hz _, 1H), 8.17-8.06 (m, 2H), 7.89 (d, J = 8.3 Hz, 1H), 7.50 (s, 1H), 7.35 (s, 1H), 7.11 (t, J = 6.2 Hz, 1H), 6.06-5.95 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H), 3.09-2.88 (m, 1H), 2.81- 2.62 (m, 2H), 2.36-2.25 (m, 1H), 2.24 (s, 3H).

Compound 78. 1-(3-bromo-4-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 9.02 (s, 1H), 8.31-8.24 (m, 1H), 8.12 (s, 1H), 7.91 (d, J = 7.4 Hz, 2H), 7.37-7.30 (m, 1H), 7.25 (t, J = 8.7 Hz, 1H), 7.04 (t, J = 6.0 Hz, 1H), 6.06-5.93 (m, 1H), 4.57 (d, J = 5.9 Hz, 2H), 3.08- 2.82 (m, 1H), 2.79-2.59 (m, 2H), 2.37-2.20 (m, 1H).

Compound 79. 1-(4-bromo-3-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.17 (s, 1H), 8.86 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.11 (d, J = 1.5 Hz, 1H) , 7.90 (dd, J = 8.2, 1.6 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.40 (d, J = 8.7 Hz, 1H), 7.22 (dd, J = 8.8, 2.7 Hz, 1H), 6.98 (t, J = 6.0 Hz, 1H), 6.04-5.91 (m, 1H), 4.57 (d, J = 6.0 Hz, 2H), 3.06-2.88 (m, 1H), 2.78-2.61 (m, 2H), 2.34-2.22 (m, 4H).

Compound 80. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-(trifluoromethyl)phenyl)urea

^1H NMR (300 MHz, CDCl ₃ ) δ 8.73 (d, J = 2.6 Hz, 1H), 8.55 (d, J = 10.8 Hz, 1H), 8.26 (t, J = 5.2 Hz, 1H), 7.69 (t , J = 8.1 Hz, 1H), 7.52-7.41 (m, 3H), 7.35 (d, J = 8.7 Hz, 2H), 7.29-7.21 (m, 1H), 6.83 (t, J = 9.0 Hz, 3H), 5.74-5.60 (m, 1H) , 4.72-4.61 (m, 1H), 3.95 (t, J = 6.4 Hz, 2H), 3.83-3.64 (m, 2H), 3.54 (dd, J = 11.3, 5.8 Hz, 3H), 3.47 (t, J = 6.2 Hz, 2H), 3.35 (q, J = 6.0 Hz, 2H), 3.00-2.73 (m, 3H), 2.70 (s, 3H), 2.42 (s, 3H), 2.39-2.28 (m, 1H), 2.01-1.89 (m, 2H), 1.85-1.78 (m, 2H), 1.69 (s, 3H), 1.66-1.61 (m, 1H), 1.61-1.47 (m, 2H).

Compound 81. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-((trifluoromethyl)thio)phenyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 9.24 (s, 1H), 8.24 (d, J = 8.1 Hz, 1H), 8.18 (d, J = 1.8 Hz, 1H) , 8.06 (dd, J = 8.4, 1.5 Hz, 1H), 7.57 (s, 4H), 7.12 (t, J = 6.0 Hz, 1H), 6.02-5.93 (m, 1H), 4.56 (d, J = 6.0 Hz, 2H), 3.03-2.89 (m, 1H) ), 2.75-2.62 (m, 2H), 2.32-2.22 (m, 1H);

LC/MS (ESI) m/z 506.9 [M+H] ⁺ , 504.9 [MH] ^- .

Compound 82. 1-(3,4-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 9.07 (s, 1H) _, 8.20 (d, J = 15.9 Hz, 1H), 8.04 (d, J = 1.9 Hz, 1H) , 7.77-7.55 (m, 1H), 7.37-7.25 (m, 1H), 7.14-7.01 (m, 2H), 6.04-5.94 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H), 3.05-2.89 (m, 1H), 2.77- 2.61 (m, 2H), 2.39-2.23 (m, 1H).

Compound 83. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(3,4,5-trifluorophenyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 9.22 ₍ s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.17 (s, 1H), 8.05 (d, J = 8.5 Hz, 1H), 7.37-7.30 (m, 2H), 7.21-7.13 (m, 1H), 6.04-5.93 (m, 1H), 4.54 (d, J = 5.8 Hz, 2H), 3.06-2.90 (m, 1H), 2.79-2.63 (m , 2H), 2.35-2.22 (m, 1H).

Compound 84. 1-(2,4-dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.21 (s, 1H), 8.39 (s, 1H), 8.26 (d, J = 8.3 Hz, 1H), 8.19 (s, 1H), 8.15 (d, J = 9.0 Hz, 1H), 8.11-8.04 (m, 1H), 7.76 (d, J = 5.9 Hz, 1H), 7.58 (d, J = 2.5 Hz, 1H), 7.38-7.29 (m, 1H), 6.08-5.95 (m, 1H), 4.59 ( d, J = 5.8 Hz, 2H), 3.09-2.90 (m, 1H), 2.82-2.61 (m, 2H), 2.35-2.22 (m, 1H).

Compound 85. 1-(3,4-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.18 (s, 1H), 9.04 (s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.11 (s, 1H), 7.94-7.88 ( m, 1H), 7.71-7.55 (m, 1H), 7.37-7.19 (m, 1H), 7.14-6.95 (m, 1H), 6.05-5.88 (m, 1H), 4.57 (d, J = 6.0 Hz, 2H), 3.07-2.83 (m, 1H) , 2.79-2.62 (m, 2H), 2.37-2.18 (m, 1H).

Compound 86. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(3,4,5-trifluorophenyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.17 (s, 1H), 9.22 ₍ s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.11 (s, 1H), 7.90 (d, J = 7.5 Hz, 1H), 7.45-7.28 (m, 2H), 7.18 (t, J = 6.0 Hz, 1H), 6.06-5.86 (m, 1H), 4.57 (d, J = 5.9 Hz, 2H), 3.10-2.87 (m, 1H), 2.79- 2.62 (m, 2H), 2.36-2.19 (m, 1H).

Compound 87. 1-(2,4-dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 8.40 (s, 1H), 8.28 (d, J = 8.2 Hz, 1H), 8.20-8.11 (m, 2H), 7.96- 7.85 (m, 1H), 7.77 (t, J = 5.8 Hz, 1H), 7.59 (d, J = 2.5 Hz, 1H), 7.34 (dd, J = 8.9, 2.5 Hz, 1H), 6.07-5.92 (m, 1H), 4.62 (d, J = 5.8 Hz, 2H), 3.08-2.87 (m, 1H), 2.82-2.61 (m, 2H), 2.33-2.25 (m, J = 8.2, 4.8 Hz, 1H).

Compound 88. 1-(4-bromo-3-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 9.19 ₍ s, 1H), 8.26 (d, J = 8.2 Hz, 1H), 8.12 (s, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.63 (dd, J = 12.1, 2.4 Hz, 1H), 7.52 (t, J = 8.5 Hz, 1H), 7.19-7.04 (m, 2H), 6.12-5.87 (m, 1H), 4.58 (d, J = 5.9 Hz, 2H), 3.09-2.87 (m, 1H), 2.81-2.62 (m, 2H), 2.35-2.22 (m, 1H).

Compound 89. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(trifluoromethyl)phenyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.20 (s, 1H), 9.52 ₍ s, 1H), 8.27 (d, J = 8.2 Hz, 1H), 8.13 (s, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.69 (d, J = 14.2 Hz, 1H), 7.62 (t, J = 8.7 Hz, 1H), 7.34-7.12 (m, 2H), 6.09-5.87 (m, 1H), 4.60 (d, J = 5.9 Hz, 2H), 3.05- 2.90 (m, 1H), 2.80-2.60 (m, 2H), 2.38-2.19 (m, 1H).

Compound 90. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-phenylurea

^1H NMR (300 MHz, Methanol- d ₄ ) δ 8.3-8.28 (m, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.10-8.04 (m, 1H), 7.42-7.36 (m, 2H) ), 7.27 (t, J = 7.9 Hz, 2H), 7.00 (t, J = 7.3 Hz, 1H), 6.02-5.93 (m, 1H), 4.65 (s, 2H), 3.02-2.80 (m, 3H), 2.50-2.35 (m, 1H).

Compound 91. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-isobutylurea

^1H NMR (300 MHz, Methanol- d ₄ ) δ 8.24 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 8.5 Hz, 1H), 6.07-5.85 (m, 1H), 4.57 (s, 2H), 3.04-2.79 (m, 4H), 2.46-2.32 (m, 1H), 2.06-2.03 (m, 1H), 1.81-1.71 (m, 1H), 1.01-0.84 (m, 6H).

Compound 92. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-methylcyclohexyl)urea

^1H NMR (500 MHz, DMSO _-d6 ) δ 11.19 (s, 1H), 8.21 (dd, J = 8.3, 3.8 Hz, 1H), 8.11-8.10 (m, 1H), 8.00-7.97 (m, 1H) ), 6.51-6.44 (m, 1H), 6.00-5.96 (m, 2H), 4.44 (dd, J = 11.3, 6.1 Hz, 2H), 3.00-2.93 (m, 1H), 2.73-2.63 (m, 2H), 2.29-2.25 (m, 1H), 1.80 (d, J = 10.2 Hz, 1H), 1.63 (d, J = 12.4 Hz, 1H), 1.53-1.51 (m, 1H), 1.48-1.43 (m, 2H), 1.28-1.05 (m, 4H), 0.98-0.84 (m, 4H).

Compound 93. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-urea

^1H NMR (500 MHz, DMSO -d6 ) δ 11.17 (s, 1H), 8.66 ₍ s, 1H), 8.23 (d, J = 7.6 Hz, 1H), 8.17 (s, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.31 (d, J = 6.6 Hz, 2H), 7.09 (d, J = 7.0 Hz, 2H), 6.86 (s, 1H), 6.00-5.96 (m, 1H), 4.53 (s, 2H), 2.99-2.92 (m, 1H), 2.81-2.78 (m, 1H), 2.73-2.65 (m, 2H), 2.30-2.24 (m, 1H), 1.16 (s, 3H), 1.15 (s, 3H).

Compound 94. 1-(4-chloro-2-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (500 MHz, _DMSO-d6 ) δ 11.19 (s, 1H), 8.69 (s, 1H), 8.24 (d, J = 8.5 Hz, 1H), 8.17 (s, 1H), 8.11 (t, J = 9.7 Hz, 1H), 8.05 (d, J = 8.5 Hz, 1H), 7.41 (d, J = 10.6 Hz, 1H), 7.34 (s, 1H), 7.17 (d, J = 8.6 Hz, 1H), 6.00-5.95 (m, 1H), 4.57 (s, 2H), 3.00-2.92 (m, 1H), 2.73-2.63 (m, 2H), 2.31-2.24 (m, 1H).

Compound 95. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 8.67 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 1.8 Hz, 1H) , 8.05 (dd, J = 8.4, 2.0 Hz, 1H), 7.35-7.26 (m, 2H), 7.10-7.01 (m, 2H), 6.87 (t, J = 6.0 Hz, 1H), 6.03-5.93 (m, 1H), 4.53 (d, J = 6.0 Hz) , 2H), 3.17 (d, J = 5.3 Hz, 1H), 3.04-2.88 (m, 1H), 2.77-2.61 (m, 3H), 2.32-2.21 (m, 1H), 1.13 (t, J = 7.6 Hz, 3H).

Compound 96. 1-(4-cyclopropylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.19 (s, 1H), 8.67 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.16 (s, 1H), 8.05 (dd, J = 8.4, 2.0 Hz, 1H), 7.28 (d, J = 8.6 Hz, 2H), 6.96-6.83 (m, 3H), 6.03-5.92 (m, 1H), 4.52 (d, J = 6.0 Hz, 2H), 2.98-2.89 (m, 1H), 2.74-2.66 (m, 2H), 2.30-2.22 (m, 2H), 1.86-1.76 (m, 1H), 0.89-0.82 (m, 2H), 0.60-0.53 (m, 2H).

Compound 97. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(trifluoromethyl)phenyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 9.06 (s, 1H), 8.24 (d, J = 8.3 Hz, 1H), 8.18 (d, J = 1.8 Hz, 1H) , 8.06 (dd, J = 8.5, 1.9 Hz, 1H), 7.89 (d, J = 2.3 Hz, 1H), 7.52-7.45 (m, 1H), 7.28 (d, J = 8.3 Hz, 1H), 7.03 (t, J = 6.0 Hz, 1H), 6.03- 5.93 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H), 3.05-2.88 (m, 1H), 2.77-2.64 (m, 2H), 2.34 (s, 3H), 2.31-2.22 (m, 1H).

Compound 98. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-isobutylphenyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.67 (s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.17 (d, J = 2.0 Hz, 1H) , 8.05 (dd, J = 8.4, 2.0 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 6.88 (t, J = 6.0 Hz, 1H), 6.03-5.93 (m, 1H), 4.53 ( d, J = 6.0 Hz, 2H), 3.04-2.90 (m, 1H), 2.76-2.62 (m, 2H), 2.35 (d, J = 7.1 Hz, 2H), 2.32-2.23 (m, 1H), 1.83-1.69 (m, 1H), 0.84 (d, J = 6.6 Hz, 6H) .

Compound 99. 1-([1,1'-biphenyl]-3-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 8.92 (s, 1H), 8.24 (d, J = 8.3 Hz, 1H), 8.19 (d, J = 1.8 Hz, 1H) , 8.07 (dd, J = 8.4, 1.9 Hz, 1H), 7.76 (t, J = 1.9 Hz, 1H), 7.63-7.56 (m, 2H), 7.50-7.41 (m, 2H), 7.41-7.28 (m, 3H), 7.23-7.16 (m, 1H) , 7.00 (t, J = 6.0 Hz, 1H), 6.03-5.95 (m, 1H), 4.56 (d, J = 6.0 Hz, 2H), 3.04-2.89 (m, 1H), 2.77-2.61 (m, 2H), 2.33-2.22 (m, 1H).

Compound 100. 1-(3-(tert-butyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 8.75 (s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 1.8 Hz, 1H) , 8.05 (dd, J = 8.4, 1.9 Hz, 1H), 7.41 (t, J = 2.0 Hz, 1H), 7.30-7.23 (m, 1H), 7.14 (t, J = 7.9 Hz, 1H), 6.98-6.91 (m, 1H), 6.87 (t, J) = 6.1 Hz, 1H), 6.03-5.94 (m, 1H), 4.54 (d, J = 6.0 Hz, 2H), 3.05-2.89 (m, 1H), 2.76-2.62 (m, 2H), 2.31-2.21 (m, 1H), 1.24 (s, 9H).

Compound 101. 1-([1,1'-biphenyl]-4-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.91 (s, 1H), 8.24 (d, J = 8.3 Hz, 1H), 8.20 (d, J = 1.8 Hz, 1H) , 8.07 (dd, J = 8.6, 2.1 Hz, 1H), 7.61 (dd, J = 7.9, 1.4 Hz, 2H), 7.59-7.48 (m, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.33-7.25 (m, 1H), 6.97 (t) , J = 6.0 Hz, 1H), 6.04-5.94 (m, 1H), 4.56 (d, J = 5.9 Hz, 2H), 3.05-2.89 (m, 1H), 2.78-2.62 (m, 2H), 2.33-2.22 (m, 1H).

Compound 102. 1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(5,6,7,8-tetrahydronaphthalen-2-yl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.56 (s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.20-8.14 (m, 1H), 8.05 ( dd, J = 8.4, 1.9 Hz, 1H), 7.13 (s, 1H), 7.07 (dd, J = 8.2, 2.3 Hz, 1H), 6.92-6.79 (m, 2H), 6.03-5.93 (m, 1H), 4.52 (d, J = 6.0 Hz, 2H) , 3.04-2.89 (m, 1H), 2.77-2.57 (m, 6H), 2.32-2.22 (m, 1H), 1.76-1.63 (m, 4H).

Compound 103. 1-(4-(tert-butyl)-3-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.19 (s, 1H), 8.91 ₍ s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 8.16 (s, 1H), 8.05 (d, J = 8.5 Hz, 1H), 7.62 (d, J = 2.5 Hz, 1H), 7.30 (d, J = 8.5 Hz, 1H), 7.19 (dd, J = 8.7, 2.7 Hz, 1H), 6.99-6.92 (m, 1H), 6.02-5.93 (m, 1H), 4.57-4.49 (m, 2H), 2.99-2.89 (m, 1H), 2.73-2.63 (m, 2H), 2.33-2.23 (m, 1H), 1.39 (s, 9H);

LC/MS (ESI) m/z 497.0[M+H] ⁺ , 494.8[MH] ^- .

Compound 104. (2,3-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.19 (s, 1H), 8.60 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.17 (s, 1H), 8.08-8.01 ( m, 1H), 7.34 (s, 1H), 7.11-7.02 (m, 2H), 6.88-6.81 (m, 1H), 6.03-5.93 (m, 1H), 4.52 (d, J = 5.9 Hz, 2H), 2.99-2.90 (m, 1H), 2.83- 2.74 (m, 4H), 2.73-2.61 (m, 2H), 2.32-2.23 (m, 1H), 2.03-1.90 (m, 2H);

LC/MS (ESI) m/z 447.0[M+H] ⁺ , 445.0[MH] ^- .

Compound 105. 1-(3-chloro-4-methylphenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)ethyl)urea

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.20 (s, 1H), 8.68 (s, 1H), 8.28-8.17 (m, 2H), 8.11 (dd, J = 8.4, 2.1 Hz, 1H), 7.60 (d, J = 2.3 Hz, 1H), 7.19-7.02 (m, 3H), 6.04-5.91 (m, 1H), 5.06-4.94 (m, 1H), 3.02-2.89 (m, 1H), 2.75-2.60 (m, 2H), 2.34-2.25 (m) , 1H), 2.21 (s, 3H), 1.46 (d, J = 7.3 Hz, 3H);

LC/MS (ESI) m/z 470.9[M+H] ⁺ , 468.0[MH] ^- .

Compound 106. 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.20 (s, 1H), 9.10 (s, 1H), 8.28-8.21 (m, 2H), 8.12 (d, J = 8.5 Hz, 1H), 8.03 ( s, 1H), 7.54 (s, 2H), 7.27 (d, J = 7.2 Hz, 1H), 6.04-5.94 (m, 1H), 5.10-4.98 (m, 1H), 3.02-2.90 (m, 1H), 2.76-2.61 (m, 3H), 2.32- 2.20 (m, 2H), 1.47 (d, J = 7.0 Hz, 3H);

LC/MS (ESI) m/z 523.9[M+H] ⁺ , 521.9[MH] ^- .

Compound 107. 1-(4-(tert-butyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.20 (s, 1H), 8.43 (s, 1H), 8.27-8.19 (m, 2H), 8.11 (dd, J = 8.4, 2.0 Hz, 1H), 7.30-7.17 (m, 4H), 6.91 (d, J = 7.3 Hz, 1H), 6.03-5.92 (m, 1H), 5.07-4.96 (m, 1H), 3.04-2.89 (m, 1H), 2.77-2.60 (m, 2H), 2.32-2.21 (m, 1H), 1.45 (d, J = 7.0 Hz, 3H), 1.22 (s, 9H);

LC/MS (ESI) m/z 477.0[M+H] ⁺ , 475.0[MH] ^- .

Compound 108. 1-([1,1'-biphenyl]-3-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)ethyl)urea

¹ H NMR (500 MHz, Acetone) δ 10.74 (s, 1H), 9.04 (d, J = 6.0 Hz, 1H), 8.93-8.83 (m, 3H), 8.56 (s, 1H), 8.32 (d, J = 7.6 Hz, 2H), 8.16 (t, J = 7.7 Hz, 3H), 8.10-7.99 (m, 2H), 7.94 (d, J = 7.4 Hz, 1H), 7.30 (d, J = 6.1 Hz, 1H), 6.76-6.66 (m, 1H), 5.99- 5.88 (m, 1H), 3.85-3.74 (m, 1H), 3.71-3.54 (m, 4H), 3.24-3.15 (m, 1H), 2.79 (d, J = 2.1 Hz, 2H), 2.31 (d, J = 7.1 Hz, 3H).

Compound 109. 1-(3-(tert-butyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea

¹ H NMR (300 MHz, Acetone) δ 10.01 (s, 1H), 8.31 (s, 1H), 8.23-8.11 (m, 2H), 7.98 (s, 1H), 7.50 (s, 1H), 7.30 (d) , J = 8.0 Hz, 1H), 7.13 (t, J = 7.9 Hz, 1H), 6.98 (d, J = 7.9 Hz, 1H), 6.49 (d, J = 6.9 Hz, 1H), 6.10-5.95 (m, 1H), 5.21 (p, J = 7.0 Hz, 1H), 3.18-2.99 (m, 1H), 2.99-2.81 (m, 2H), 2.57-2.39 (m, 1H), 1.56 (d, J = 7.0 Hz, 3H), 1.26 (s, 9H).

Compound 110. 1-(4-(tert-butyl)-3-chlorophenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (500 MHz, DMSO) δ 11.22 (s, 1H), 8.68 (s, 1H), 8.29-8.19 (m, 2H), 8.12 (dd, J = 8.5, 2.0 Hz, 1H), 7.57 (d) , J = 2.4 Hz, 1H), 7.28 (d, J = 8.7 Hz, 1H), 7.13 (dd, J = 8.7, 2.4 Hz, 1H), 7.05 (d, J = 7.2 Hz, 1H), 6.00 (dd, J = 12.2, 5.8 Hz, 1H) , 5.02 (p, J = 6.9 Hz, 1H), 3.04-2.92 (m, 1H), 2.76-2.63 (m, 2H), 2.33-2.22 (m, 1H), 1.46 (d, J = 7.0 Hz, 3H), 1.39 (s, 9H).

Compound 111. 1-(4-(tert-butyl)-3-chlorophenyl)-3-(2-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)propan-2-yl)urea

^1H NMR (500 MHz, DMSO) δ 11.20 (s, 1H), 8.66 (s, 1H), 8.26-8.20 (m, 2H), 8.17 (d, J = 8.5 Hz, 1H), 7.53 (d, J = 2.1 Hz, 1H), 7.27 (d, J = 8.7 Hz, 1H), 7.04 (dd, J = 8.6, 2.0 Hz, 1H), 6.98 (s, 1H), 6.04-5.93 (m, 1H), 3.03-2.89 (m, 2H), 2.77-2.62 (m , J = 25.6, 13.7 Hz, 3H), 2.34-2.25 (m, 1H), 1.68 (s, 6H), 1.38 (s, 9H).

Compound 112. 1-(4-(tert-butyl)benzyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO) δ 11.20 (s, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.15 (s, 1H), 8.01 (d, J = 8.3 Hz, 1H), 7.33 ( d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.2 Hz, 2H), 6.72 (t, J = 5.9 Hz, 1H), 6.62 (t, J = 5.8 Hz, 1H), 5.99 (dd, J = 12.3, 5.3 Hz, 1H), 4.47 (d, J = 6.0 Hz, 2H), 4.20 (d, J = 5.9 Hz, 2H), 3.05-2.90 (m, 1H), 2.79-2.63 (m, 2H), 2.38-2.20 (m, 1H), 1.26 (s, 9H).

Compound 113. 1-(4-(tert-butyl)benzyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (300 MHz, DMSO) δ 11.21 (s, 1H), 8.27-8.16 (m, 2H), 8.07 (d, J = 8.4 Hz, 1H), 7.30 (d, J = 8.1 Hz, 2H), 7.13 (d, J = 8.2 Hz, 2H), 6.76 (dd, J = 7.4, 2.7 Hz, 1H), 6.39 (t, J = 5.6 Hz, 1H), 6.10-5.93 (m, 1H), 4.96 (p, J = 6.9 Hz, 1H), 4.14 (d , J = 5.3 Hz, 2H), 3.08-2.92 (m, J = 19.5 Hz, 1H), 2.83-2.61 (m, 2H), 2.35-2.21 (m, 1H), 1.40 (d, J = 7.0 Hz, 3H), 1.25 (d, J = 1.3 Hz, 9H).

Compound 114. 1-(3-bromo-4-(tert-butyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (500 MHz, DMSO _-d6 ) δ 11.19 (s, 1H), 8.63 (s, 1H), 8.28-8.20 (m, 2H), 8.11 (m, 1H), 7.80 (m, 1H), 7.29 (d, J = 8.9 Hz, 1H), 7.17 (m, 1H), 7.01 (d, J = 7.3 Hz, 1H), 6.03-5.91 (m, 1H), 5.01 (q, J = 7.1 Hz, 1H), 3.04-2.89 (m, 1H), 2.70 (m, 2H), 2.27 (m, 1H), 1.46 (d, J = 7.1 Hz, 3H), 1.41 (s, 9H).

Compound 115. 1-(2-(4-chlorophenyl)propan-2-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (500 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.21 (d, J = 8.4 Hz, 1H), 8.17 (s, 1H), 8.02 (d, J = 8.4 Hz, 1H) , 7.34-7.28 (m, 2H), 7.25 (d, J = 8.5 Hz, 2H), 6.61 (d, J = 7.5 Hz, 1H), 6.46 (d, J = 5.4 Hz, 1H), 6.01 (m, 1H), 4.82 (m, 1H), 2.99 (m, 1H), 2.77-2.64 (m, 2H), 2.34-2.23 (m, 1H), 1.52 (d, J = 6.2 Hz, 3H), 1.44 (d, J = 5.4 Hz, 3H), 1.37 (d, J = 7.0 Hz, 3H).

Compound 116. 1-(1-(4-chlorophenyl)ethyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (500 MHz, DMSO _-d6 ) δ 11.20 (s, 1H), 8.19 (m, 2H), 8.03 (m, 1H), 7.40-7.22 (m, 4H), 6.62 (m, 1H), 6.46 (m, 1H), 6.00 (s, 1H), 4.89 (m, 1H), 4.66 (m, 1H), 2.96 (m, 1H), 2.68 (m, 2H), 2.28 (s, 1H), 1.38 (t, J = 7.7 Hz, 3H), 1.29 (dd, J = 11.4, 7.1 Hz, 3H).

Compound 117. 1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(5,6,7,8-tetrahydronaphthalen-2-yl)urea

^1H NMR (300 MHz, DMSO) δ 11.19 (s, 1H), 8.31 (s, 1H), 8.28-8.19 (m, 2H), 8.11 (dd, J = 8.4, 1.9 Hz, 1H), 7.08 (s) , 1H), 7.01 (dd, J = 8.3, 2.2 Hz, 1H), 6.92-6.83 (m, 2H), 6.04-5.92 (m, 1H), 5.00 (p, J = 7.2 Hz, 1H), 3.08-2.87 (m, 1H), 2.79-2.67 (m , 2H), 2.67-2.56 (m, 4H), 2.33-2.20 (m, 1H), 1.68 (brs, 4H), 1.45 (d, J = 7.0 Hz, 3H).

Compound 118. 1-(2,3-dihydro-1H-indene-5-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (300 MHz, DMSO) δ 11.20 (s, 1H), 8.37 (s, 1H), 8.29-8.18 (m, 2H), 8.11 (dd, J = 8.4, 1.9 Hz, 1H), 7.29 (s) , 1H), 7.04 (d, J = 1.0 Hz, 2H), 6.89 (d, J = 7.2 Hz, 1H), 6.06-5.92 (m, 1H), 5.01 (p, J = 6.9 Hz, 1H), 3.07-2.89 (m, 1H), 2.83-2.60 (m, 6H), 2.30 (d, J = 17.6 Hz, 1H), 2.06-1.88 (m, 2H), 1.46 (d, J = 7.0 Hz, 3H).

Compound 119. 1-(4-chloro-3-methylphenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)ethyl)urea

^1H NMR (300 MHz, DMSO) δ 11.20 (s, 1H), 8.59 (s, 1H), 8.30-8.21 (m, 2H), 8.12 (dd, J = 8.4, 1.9 Hz, 1H), 7.36 (s) , 1H), 7.27-7.16 (m, 2H), 7.01 (d, J = 7.2 Hz, 1H), 6.07-5.90 (m, 1H), 5.02 (p, J = 6.7 Hz, 1H), 3.08-2.90 (m, 1H), 2.78-2.64 (m) , 2H), 2.34-2.20 (m, 4H), 1.46 (d, J = 7.0 Hz, 3H).

Compound 120. 1-(3-(tert-butyl)-4-chlorophenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (500 MHz, DMSO) δ 11.20 (s, 1H), 8.68 (s, 1H), 8.28-8.20 (m, 2H), 8.12 (dd, J = 8.4, 1.9 Hz, 1H), 7.48 (d) , J = 2.1 Hz, 1H), 7.28 (dd, J = 8.6, 2.5 Hz, 1H), 7.19 (d, J = 8.6 Hz, 1H), 6.99 (d, J = 7.2 Hz, 1H), 6.04-5.95 (m, 1H), 5.03 (dd, J = 14.1, 7.0 Hz, 1H), 3.04-2.92 (m, 1H), 2.77-2.62 (m, 2H), 2.33-2.20 (m, 1H), 1.46 (d, J = 7.0 Hz, 3H), 1.40 (s, 9H).

Compound 121. 1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(3'-methyl-[1,1'-biphenyl]-3-yl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.66 (s, 1H), 8.25 (d, J = 8.4 Hz, 2H), 8.13 (dd, J = 8.4, 2.0 Hz, 1H), 7.71 (m, 1H), 7.41-7.31 (m, 3H), 7.29-7.26 (m, 2H), 7.20-7.12 (m, 2H), 7.04 (d, J = 7.2 Hz, 1H), 5.99 (m, 1H), 5.03 (q, J = 7.1 Hz, 1H), 2.97 (m, 1H), 2.76-2.63 (m, 2H), 2.35 (s, 3H), 2.32-2.20 (m, 1H), 1.47 (d, J = 7.0 Hz, 3H).

Compound 122. 1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(9H-fluoren-3-yl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.65 (s, 1H), 8.25 (d, J = 8.3 Hz, 2H), 8.14 (dd, J = 8.5, 2.0 Hz, 1H), 7.80-7.67 (m, 3H), 7.50 (d, J = 7.4 Hz, 1H), 7.34-7.27 (m, 2H), 7.21 (m, 1H), 7.02 (d, J = 7.2 Hz, 1H), 6.07-5.90 (m, 1H), 5.06 (q, J = 6.9 Hz, 1H), 3.83 (s, 2H), 2.98 (m, 1H), 2.76-2.61 (m, 2H), 2.27 (s, 1H), 1.48 (d, J = 7.0 Hz, 3H).

Compound 123. 1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(2'-methyl-[1,1'-biphenyl]-3-yl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.20 (s, 1H), 8.62 (s, 1H), 8.24 (d, J = 8.4 Hz, 2H), 8.12 (dd, J = 8.5, 2.0 Hz, 1H), 7.37 (m, 1H), 7.33-7.14 (m, 6H), 7.02 (d, J = 7.2 Hz, 1H), 6.85 (m, 1H), 5.98 (m, 1H), 5.09-4.96 (m, 1H), 2.98 (m, 1H) , 2.74-2.63 (m, 2H), 2.28 (m, 2H), 2.20 (s, 3H), 1.46 (d, J = 7.0 Hz, 3H).

Compound 124. 1-(3-(benzo[d]thiazol-2-yl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.19 (s, 1H), 8.89 (s, 1H), 8.34 (m, 1H), 8.30-8.22 (m, 2H), 8.18-8.10 (m, 2H) ), 8.05 (m, 1H), 7.66-7.37 (m, 5H), 7.09 (d, J = 7.1 Hz, 1H), 6.05-5.92 (m, 1H), 5.06 (q, J = 6.9 Hz, 1H), 2.98 (m, 1H), 2.76 -2.60 (m, 2H), 2.29 (m, 1H), 1.50 (d, J = 7.0 Hz, 3H).

Compound 125. 1-(4'-chloro-[1,1'-biphenyl]-3-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.19 (s, 1H), 8.71 ₍ s, 1H), 8.25 (d, J = 8.4 Hz, 2H), 8.13 (dd, J = 8.5, 2.0 Hz, 1H), 7.95-7.87 (m, 2H), 7.84-7.73 (m, 3H), 7.43-7.32 (m, 2H), 7.30-7.21 (m, 1H), 7.08 (d, J = 7.0 Hz, 1H), 6.05-5.91 (m, 1H), 5.05 ( m, 1H), 2.98 (m, 1H), 2.79-2.58 (m, 2H), 2.28 (m, 1H), 1.48 (d, J = 7.0 Hz, 3H).

Compound 126. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylacetate

LC/MS (ESI) m/z 583 [M+H] ⁺ .

Compound 127. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylisobutyrate

LC/MS (ESI) m/z 611 [M+H] ⁺ .

Compound 128. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylcyclopentanecarboxylate

LC/MS (ESI) m/z 637 [M+H] ⁺ .

Compound 129. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylprolanate

LC/MS (ESI) m/z 638 [M+H] ⁺ .

Compound 130. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methyl methyl carbonate

LC/MS (ESI) m/z 599 [M+H] ⁺ .

Compound 131. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methyl methyl carbonate

LC/MS (ESI) m/z 627 [M+H] ⁺ .

Compound 132. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylpiperidin-4-ylcarbonate

LC/MS (ESI) m/z 668 [M+H] ⁺ .

Compound 133. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2-(2-methoxyethoxy)ethoxy)ethyl)carbonate

LC/MS (ESI) m/z 731 [M+H] ⁺ .

Compound 134. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2-acetamidoethyl)carbamate

LC/MS (ESI) m/z 669 [M+H] ⁺ .

Compound 135. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2-((R)-2-amino-3-methylbutanamido)ethyl)carbamate

^1H NMR (500 MHz, MeOH- d ₄ ) δ 8.33 (s, 1H), 8.21 (d, J = 8.4 Hz, 1H), 8.11 (d, J = 8.8 Hz, 1H), 7.48 (m, 1H) , 7.34 (d, J = 8.7 Hz, 1H), 7.16 (dd, J = 8.7, 2.3 Hz, 1H), 5.97 (m, 1H), 5.13 (m, 2H), 4.86-4.77 (m, 2H), 3.92 (m, 2H), 3.76 (t, J = 5.6 Hz, 2H), 3.72-3.63 (m, 7H), 3.02-2.81 (m, 3H), 2.40 (m, 2H), 1.57 (d, J = 7.0 Hz, 3H), 1.45 (s, 9H), 1.14 (s, 2H), 1.01 (d, J = 7.1 Hz, 3H).

Compound 136. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2,6-dioxopiperidin-1-yl)methyl(2-aminoethyl)carbamate

LC/MS (ESI) m/z 627[M+H] ⁺ .

Compound 137. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2,6-dioxopiperidin-1-yl)methylvalinate

LC/MS (ESI) m/z 640 [M+H] ⁺ .

Compound 138. (3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylhistinoate

LC/MS (ESI) m/z 678[M+H] ⁺ .

Compound 139. 3-(7-(aminomethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-yl)piperidine-2,6-dione

^1H NMR (500 MHz, DMSO- d ₆ ) δ 11.22 (s, 1H), 8.65 (s, 3H), 8.40 (d, J = 1.5 Hz, 1H), 8.33 (d, J = 8.1 Hz, 1H) , 8.06 (dd, J = 8.2, 1.6 Hz, 1H), 6.02 5.99 (m, 1H), 4.35 (q, J = 5.7 Hz, 2H), 3.02-2.94 (m, 1H), 2.75-2.66 (m, 2H), 2.32-2.27 (m, 1H).

Compound 140. 3-(6-(aminomethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-yl)piperidine-2,6-dione

^1H NMR (500 MHz, DMSO -d6 ) δ 11.22 (s, 1H), 8.57 (s, 3H) _, 8.44 (d, J = 1.9 Hz, 1H), 8.33 (d, J = 8.4 Hz, 1H) , 8.22 (dd, J = 8.5, 1.9 Hz, 1H), 6.05-6.00 (m, 1H), 4.32 (q, J = 5.9 Hz, 2H), 3.02-2.94 (m, 1H), 2.76-2.67 (m, 2H), 2.32-2.28 (m, 1H) .

Compound 141. 3-(5-( Aminomethyl )-4- Oxobenzo[d][1,2,3]triazine -3(4H)-yl)piperidine-2,6-dione

^1H NMR (500 MHz, DMSO- d ₆ ) δ 11.24 (s, 1H), 8.36 (s, 3H), 8.32 (d, J = 8.1 Hz, 1H), 8.19 (t, J = 7.8 Hz, 1H) , 7.99 (d, J = 7.5 Hz, 1H), 6.04-6.01 (m, 1H), 4.66-4.55 (m, 2H), 3.01-2.93 (m, 1H), 2.73-2.63 (m, 2H), 2.29-2.23 (m, 1H).

Compound 142. 1-(3-chloro-4-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.06 (s, 1H), 8.81 (s, 1H), 8.17 (d, J = 8.3 Hz, 1H), 7.68 (s, 1H), 7.55 (s, 1H), 7.49-7.38 (m, 2H), 7.22-7.12 (m, 2H), 6.84 (t, J = 5.8 Hz, 1H), 6.67 (d, J = 7.4 Hz, 1H), 5.62-5.39 (m, 1H), 4.44 (d, J = 5.8 Hz) , 2H), 2.90-2.78 (m, 1H), 2.67-2.57 (m, 2H), 2.24 (s, 3H), 2.10-1.98 (m, 1H).

Compound 143. 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.05 (s, 1H), 9.26 ₍ s, 1H), 8.17 (d, J = 8.3 Hz, 1H), 8.10 (s, 1H), 7.63 (d, J = 9.1 Hz, 1H), 7.56 (d, J = 6.4 Hz, 2H), 7.44 (dd, J = 15.5, 7.9 Hz, 2H), 7.04 (s, 1H), 6.67 (d, J = 7.4 Hz, 1H), 5.60-5.42 (m, 1H), 4.46 ( d, J = 5.9 Hz, 2H), 2.88-2.78 (m, 1H), 2.74-2.59 (m, 2H), 2.12-1.94 (m, 1H).

Compound 144. 1-(3-chloro-4-methoxyphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.05 (s, 1H), 8.70 (s, 1H), 8.17 (d, J = 8.6 Hz, 1H), 7.65 (s, 1H), 7.55 (s, 1H), 7.49-7.37 (m, 2H), 7.26-7.18 (m, 1H), 7.04 (d, J = 8.7 Hz, 1H), 6.81 (s, 1H), 6.67 (d, J = 7.0 Hz, 1H), 5.61-5.40 (m, 1H), 4.44 (s, 2H), 3.79 (s, 3H), 2.93-2.78 (m, 1H), 2.76-2.63 (m, 2H), 2.10-1.93 (m, 1H).

Compound 145. 1-(3-chloro-4-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.05 (s, 1H), 8.79 (s, 1H), 8.14 (s, 1H), 7.71-7.62 (m, 3H), 7.39 (d, J = 7.3 Hz, 1H), 7.21-7.11 (m, 2H), 6.89-6.83 (m, 1H), 6.67 (d, J = 7.5 Hz, 1H), 5.60-5.44 (m, 1H), 4.42 (d, J = 5.9 Hz, 2H), 2.90-2.78 (m , 2H), 2.76-2.60 (m, 1H), 2.24 (s, 3H), 2.11-1.97 (m, 1H).

Compound 146. 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-6-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.03 (s, 1H), 9.31-9.21 (m, 1H), 8.17-8.07 (m, 2H), 7.73-7.51 (m, 4H), 7.39 (d) , J = 7.4 Hz, 1H), 7.17-7.01 (m, 1H), 6.67 (d, J = 7.4 Hz, 1H), 5.58-5.38 (m, 1H), 4.44 (d, J = 5.9 Hz, 2H), 2.94-2.80 (m, 2H) , 2.74-2.59 (m, 1H), 2.11-1.92 (m, 1H).

Compound 147. 1-(3,4-dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, Chloroform- d ) δ 8.53 (s, 0.5H), 8.44 (s, 0.5H), 8.17 (t, J = 4.0 Hz, 1H), 7.68 (t, J = 8.1 Hz, 1H) ), 7.40 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.5 Hz, 1H), 6.57-6.45 (m, 1H), 5.71-5.61 (m, 1H), 4.61 (t, J = 7.0 Hz) , 1H), 3.55 (dd, J = 14.1, 7.8 Hz, 1H), 3.32 (dd, J = 14.1, 6.5 Hz, 2H), 3.21 (q, J = 6.6 Hz, 3H), 3.02-2.73 (m, 3H), 2.66 (s, 3H), 2.40 (s, 3H), 2.34- 2.30 (m, 1H), 1.67 (s, 3H), 1.57-1.18 (m, 14H).

Compound 148. 1-(3,5-dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, Chloroform- d ) δ 8.65 (d, J = 20.6 Hz, 1H), 8.17 (dd, J = 8.8, 5.2 Hz, 1H), 7.68 (t, J = 8.2 Hz, 1H), 7.40 (d, J = 8.6 Hz, 2H), 7.32 (d, J = 8.5 Hz, 2H), 6.78 (d, J = 8.5 Hz, 1H), 6.67-6.53 (m, 1H), 5.71-5.59 (m, 1H), 4.61 (t, J = 7.1 Hz) , 1H), 3.62-3.47 (m, 1H), 3.39-3.26 (m, 2H), 3.26-3.15 (m, 3H), 3.00-2.72 (m, 3H), 2.66 (s, 3H), 2.39 (s, 3H), 2.37-2.28 (m, 1H), 1.71 (s, 3H) , 1.52-1.22 (m, 12H).

Compound 149. 1-(2,3-dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, Chloroform- d ) δ 8.27 (t, J = 5.3 Hz, 1H), 8.16 (s, 1H), 7.68 (t, J = 8.1 Hz, 1H), 7.40 (d, J = 8.6) Hz, 2H), 7.32 (d, J = 8.7 Hz, 2H), 7.24 (d, J = 7.7 Hz, 1H), 6.77 (d, J = 8.5 Hz, 1H), 6.57 (t, J = 6.0 Hz, 1H), 5.79-5.63 (m, 1H), 4.66- 4.55 (m, 1H), 3.57 (dd, J = 14.1, 7.8 Hz, 1H), 3.33 (dd, J = 14.1, 6.2 Hz, 1H), 3.28-3.15 (m, 1H), 3.14-3.03 (m, 2H), 3.04-2.97 (m, 1H), 2.97-2.88 (m, 1H), 2.89-2.83 (m, 1H), 2.83-2.76 (m, 1H), 2.67 (s, 3H), 2.40 (s, 3H), 2.37-2.30 (m, 1H), 2.03 (d, J = 5.9 Hz, 1H), 1.97-1.75 (m, 4H), 1.67 (s, 3H), 1.26 (s, 2H), 1.14-0.93 (m, 4H).

Compound 150. 1-(2-chloro-4-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, Chloroform -d ) δ 9.00 (s, 0.5H), 8.93 (s, 0.5H), 8.43-8.33 (m, 1H), 7.66 (t, J = 8.2 Hz, 1H), 7.46 -7.36 (m, 2H), 7.36-7.28 (m, 2H), 7.13-6.94 (m, 1H), 6.80 (d, J = 8.4 Hz, 1H), 5.74-5.57 (m, 1H), 4.65 (t, J = 7.0 Hz, 1H) , 3.78 (t, J = 5.3 Hz, 2H), 3.73-3.56 (m, 12H), 3.50 (t, J = 5.7 Hz, 2H), 3.45-3.37 (m, 2H), 2.96-2.82 (m, 3H), 2.66 (s, 3H), 2.39 (s, 3H), 2.35-2.27 (m, 1H) ), 1.66 (s, 3H).

Compound 151. 1-(4-bromo-3-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, Chloroform- d ) δ 8.90 (s, 0.5H), 8.80 (s, 0.5H), 8.21 (t, J = 5.3 Hz, 1H), 7.70 (t, J = 8.1 Hz, 1H) ), 7.42 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.5 Hz, 1H), 6.71-6.62 (m, 1H), 5.72-5.57 (m, 1H), 4.70-4.58 (m, 1H) , 3.66-3.50 (m, 1H), 3.42-3.16 (m, 5H), 3.01-2.73 (m, 3H), 2.68 (s, 3H), 2.41 (s, 3H), 2.38-2.29 (m, 1H), 1.68 (s, 3H), 1.61-1.19 (m, 10H).

Compound 152. 1-(4-(tert-butyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO - _d6 ) δ 11.02 (s, 1H), 8.53 (s, 1H), 8.13 (s, 1H), 7.71-7.61 (m, 2H), 7.42-7.18 (m, 5H) ), 6.74-6.61 (m, 2H), 5.57-5.40 (m, 1H), 4.42 (d, J = 6.0 Hz, 2H), 2.89-2.80 (m, 1H), 2.66-2.59 (m, 2H), 2.09-1.96 (m, 1H), 1.24 ( s, 9H).

Compound 153. 1-(3-chlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.02 (s, 1H), 8.87 (s, 1H), 8.14 (s, 1H), 7.71-7.60 (m, 3H), 7.38 (d, J = 7.5 Hz, 1H), 7.23 (d, J = 6.4 Hz, 2H), 6.94 (dd, J = 6.2, 2.7 Hz, 1H), 6.86 (t, J = 6.0 Hz, 1H), 6.66 (d, J = 7.4 Hz, 1H), 5.62-5.34 (m, 1H) ), 4.43 (d, J = 5.9 Hz, 2H), 2.91-2.79 (m, 1H), 2.73-2.55 (m, 2H), 2.09-1.98 (m, 1H).

Compound 154. 1-(4-chlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, Chloroform -d ) δ 7.65 (t, J = 8.0 Hz, 1H), 7.37 (dd, J = 7.8, 0.9 Hz, 1H), 6.88 (dd, J = 8.3, 0.9 Hz, 1H) ), 6.14 (s, 2H), 5.88 (s, 2H), 5.82-5.74 (m, 1H), 3.17-2.87 (m, 3H), 2.45-2.32 (m, 1H), 1.21 (s, 9H).

Compound 155. 1-(4-bromo-2-chloro-6-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, Chloroform -d ) δ 8.06-7.99 (m, 2H), 7.62 (t, J = 8.0 Hz, 1H), 7.59-7.52 (m, 1H), 7.46-7.39 (m, 2H) , 7.34 (dd, J = 7.8, 0.9 Hz, 1H), 6.85 (dd, J = 8.3, 0.9 Hz, 1H), 6.19-6.03 (m, 4H), 5.83-5.74 (m, 1H), 3.19-2.85 (m, 3H), 2.45-2.33 ( m, 1H).

Compound 156. 1-(4-bromo-2-chloro-6-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, Chloroform -d ) δ 7.63 (t, J = 8.0 Hz, 1H), 7.37-7.33 (m, 1H), 6.89-6.81 (m, 1H), 6.14 (s, 2H), 5.87 (s, 2H), 5.78-5.72 (m, 1H), 3.82-3.58 (m, 1H), 3.19-3.01 (m, 3H), 2.99-2.82 (m, 2H), 2.70-2.57 (m, 2H), 2.55-2.29 (m, 2H) , 1.89 (d, J = 13.3 Hz, 2H), 1.75-1.55 (m, 2H).

Compound 157. 1-(4-chlorobenzyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, Chloroform- d ) δ 7.66 (t, J = 8.0 Hz, 1H), 7.37 (d, J = 7.8 Hz, 1H), 6.89 (d, J = 8.2 Hz, 1H), 6.15 ( s, 2H), 5.93 (s, 1H), 5.80-5.69 (m, 1H), 3.15-2.85 (m, 4H), 2.38 (d, J = 6.6 Hz, 1H), 2.23-1.99 (m, 1H), 1.91 (dd, J = 13.5, 7.1 Hz, 1H), 1.84-1.78 (m, 3H).

Compound 158. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-fluorophenethyl)urea

^1H NMR (300 MHz, Chloroform- d ) δ 7.69-7.61 (m, 1H), 7.36 (d, J = 7.8 Hz, 1H), 6.88 (d, J = 8.3 Hz, 1H), 6.16 (s, 2H) ), 5.92 (s, 2H), 5.83-5.71 (m, 1H), 3.37 (d, J = 5.0 Hz, 1H), 3.18-2.82 (m, 3H), 2.48-2.30 (m, 1H), 1.54-1.38 (m, 1H), 1.27- 1.08 (m, 2H), 0.95 (d, J = 6.8 Hz, 2H), 0.94-0.85 (m, 4H).

Compound 159. 1-(2,6-dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, Chloroform -d ) δ 7.62 (t, J = 8.1 Hz, 1H), 7.37-7.31 (m, 1H), 6.89-6.82 (m, 1H), 6.14 (s, 2H), 5.86 (d, J = 2.2 Hz, 2H), 5.81-5.71 (m, 1H), 3.16-3.03 (m, 1H), 2.98-2.86 (m, 2H), 2.44-2.33 (m, 1H), 2.29 (t, J = 7.4 Hz, 2H), 1.71- 1.63 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H).

Compound 160. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(m-tolyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.03 (s, 1H), 8.57 (s, 1H), 8.13 ₍ s, 1H), 7.71-7.61 (m, 2H), 7.38 (d, J = 7.4 Hz, 1H), 7.26 (s, 1H), 7.18 (d, J = 8.3 Hz, 1H), 7.09 (t, J = 7.7 Hz, 1H), 6.77 (t, J = 6.0 Hz, 1H), 6.71 (d, J = 7.4 Hz, 1H), 6.66 ( d, J = 7.4 Hz, 1H), 5.62-5.36 (m, 1H), 4.42 (d, J = 5.9 Hz, 2H), 2.91-2.79 (m, 1H), 2.67-2.58 (m, 2H), 2.24 (s, 3H), 2.10-1.97 (m, 1H).

Compound 161. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-fluoro-3-methylphenyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.02 (s, 1H), 8.58 ( _s , 1H), 8.13 (s, 1H), 7.71-7.59 (m, 2H), 7.38 (d, J = 7.5 Hz, 1H), 7.31 (dd, J = 7.0, 2.7 Hz, 1H), 7.24-7.16 (m, 1H), 6.98 (t, J = 9.2 Hz, 1H), 6.75 (t, J = 6.0 Hz, 1H), 6.66 (d, J = 7.4 Hz, 1H) , 5.62-5.37 (m, 1H), 4.41 (d, J = 5.9 Hz, 2H), 2.94-2.78 (m, 1H), 2.68-2.56 (m, 2H), 2.23-2.13 (m, 3H), 2.10-1.99 (m, 1H).

Compound 162. 1-(3,4-dimethylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (500 MHz, DMSO- d ₆ ) δ 11.04 (s, 1H), 8.46 (s, 1H), 8.14 (s, 1H), 7.70-7.61 (m, 2H), 7.39 (d, J = 7.4 Hz, 1H), 7.19 (d, J = 2.3 Hz, 1H), 7.12 (dd, J = 8.1, 2.3 Hz, 1H), 6.97 (d, J = 8.1 Hz, 1H), 6.72 (t, J = 6.1 Hz, 1H), 6.67 (d, J = 7.4 Hz, 1H), 5.71-5.27 (m, 1H), 4.41 (d, J = 6.0 Hz, 2H), 2.92-2.82 (m, 1H), 2.65-2.60 (m, 2H), 2.16 (s, 3H), 2.13 (s, 3H), 2.08-2.01 (m, 1H).

Compound 163. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-((trifluoromethyl)thio)phenyl)urea

^1H NMR (500 MHz, DMSO - _d6 ) δ 11.04 (s, 1H), 9.13 (s, 1H), 8.14 (s, 1H), 7.70-7.58 (m, 3H), 7.58-7.53 (m, 3H) ), 7.38 (d, J = 7.4 Hz, 1H), 7.00 (s, 1H), 6.66 (d, J = 7.4 Hz, 1H), 5.66-5.30 (m, 1H), 4.44 (d, J = 6.0 Hz, 2H), 2.92-2.80 (m, 1H) ), 2.66-2.58 (m, 2H), 2.07-2.00 (m, 1H).

Compound 164. 1-(benzo[d][1,3]dioxol-5-ylmethyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (500 MHz, DMSO- d ₆ ) δ 11.05 (s, 1H), 8.10 (s, 1H), 7.62 (d, J = 1.2 Hz, 2H), 7.38 (d, J = 7.4 Hz, 1H) , 6.83 (d, J = 7.9 Hz, 1H), 6.81 (d, J = 1.6 Hz, 1H), 6.73 (dd, J = 8.0, 1.7 Hz, 1H), 6.65 (d, J = 7.4 Hz, 1H), 6.56 (t, J = 6.1 Hz, 1H), 6.45 (t, J = 6.1 Hz, 1H), 5.96 (s, 2H), 5.68-5.31 (m, 1H), 4.35 (d, J = 6.1 Hz, 2H), 4.13 (d, J = 6.0 Hz, 2H), 2.93-2.82 (m, 1H), 2.69-2.58 (m, 2H), 2.08- 2.01 (m, 1H).

Compound 165. 1-(benzo[d]thiazol-6-yl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO _-d6 ) δ 11.02 (s, 1H), 9.16 (s, 1H), 8.95 (s, 1H), 8.33 (d, J = 2.3 Hz, 1H), 8.16 (s, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.74-7.61 (m, 2H), 7.45-7.34 (m, 2H), 6.92-6.84 (m, 1H), 6.66 (d, J = 7.3 Hz, 1H), 5.57-5.41 (m, 1H) , 4.46 (d, J = 5.8 Hz, 2H), 2.88-2.82 (m, 1H), 2.75-2.65 (m, 3H), 2.09-1.99 (m, 1H).

Compound 166. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(p-tolyl)urea

^1H NMR (500 MHz, DMSO -d6 ) δ 11.04 (s, 1H), 8.55 (s, 1H), 8.13 ₍ s, 1H), 7.70-7.62 (m, 2H), 7.38 (d, J = 7.4 Hz, 1H), 7.31-7.27 (m, 2H), 7.02 (d, J = 8.2 Hz, 2H), 6.74 (t, J = 6.0 Hz, 1H), 6.66 (d, J = 7.5 Hz, 1H), 5.62-5.36 (m, 1H), 4.41 ( d, J = 6.0 Hz, 2H), 2.91-2.81 (m, 1H), 2.67-2.57 (m, 3H), 2.21 (s, 3H), 2.08-2.00 (m, 1H).

Compound 167. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(3,4,5-trifluorophenyl)urea

^1H NMR (300 MHz, DMSO - _d6 ) δ 11.02 (s, 1H), 9.11 (s, 1H), 8.13 (s, 1H), 7.70-7.58 (m, 3H), 7.50 (t, J = 8.5 Hz, 1H), 7.38 (d, J = 7.4 Hz, 1H), 7.08 (d, J = 8.6 Hz, 1H), 7.01 (s, 1H), 6.66 (d, J = 7.3 Hz, 1H), 5.57-5.39 (m, 1H), 4.42 (d, J = 5.8 Hz, 2H), 2.89-2.77 (m, 2H), 2.67-2.58 (m, 3H), 2.11-1.96 (m, 1H).

Compound 168. 1-(4-bromo-3-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO - _d6 ) δ 11.02 (s, 1H), 9.19 (s, 1H), 8.12 (s, 1H), 7.68-7.60 (m, 2H), 7.41-7.28 (m, 3H) ), 7.19-7.09 (m, 1H), 6.66 (d, J = 7.3 Hz, 1H), 5.59-5.40 (m, 1H), 4.42 (d, J = 5.9 Hz, 2H), 2.89-2.80 (m, 1H), 2.65-2.58 (m, 2H) , 2.09-1.99 (m, 1H).

Compound 169. 1-(3-chloro-4-methoxyphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (500 MHz, DMSO- d ₆ ) δ 11.04 (s, 1H), 8.66 (s, 1H), 8.16-8.10 (m, 1H), 7.69-7.60 (m, 3H), 7.38 (d, J = 7.5 Hz, 1H), 7.21 (dd, J = 8.9, 2.6 Hz, 1H), 7.03 (d, J = 9.0 Hz, 1H), 6.80 (t, J = 6.0 Hz, 1H), 6.66 (d, J = 7.4 Hz, 1H), 5.65-5.27 (m, 1H), 4.41 (d, J = 6.0 Hz, 2H), 3.78 (s, 3H), 2.93-2.81 (m, 1H), 2.69-2.58 (m, 3H), 2.08-2.00 (m, 1H).

Compound 170. 1-(3-chloro-4-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

¹ H NMR (300 MHz, CD ₃ OD) δ 8.26 (s, 1H), 7.77-7.70 (m, 1H), 7.66 (dd, J = 7.2, 2.2 Hz, 2H), 7.32 (d, J = 7.4 Hz) , 1H), 7.29-7.21 (m, 1H), 7.13 (t, J = 8.9 Hz, 1H), 6.74 (d, J = 7.5 Hz, 1H), 5.46-5.35 (m, 1H), 4.55 (s, 2H), 2.94-2.69 (m, 3H) ), 2.27-2.17 (m, 1H).

Compound 171. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-methoxyphenyl)urea

^1H NMR (500 MHz, DMSO -d6 ) δ 11.04 (s, 1H), 8.44 (s, 1H), 8.13 ₍ s, 1H), 7.69-7.61 (m, 2H), 7.38 (d, J = 7.5 Hz, 1H), 7.32-7.29 (m, 2H), 6.83-6.79 (m, 2H), 6.69-6.64 (m, 2H), 5.62-5.32 (m, 1H), 4.41 (d, J = 6.0 Hz, 2H), 3.69 (s, 3H), 2.91 -2.79 (m, 1H), 2.66-2.57 (m, 2H), 2.07-2.01 (m, 1H).

Compound 172. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(3-fluoro-4-(trifluoromethyl)phenyl)urea

^1H NMR (300 MHz, DMSO - _d6 ) δ 11.03 (s, 1H), 9.40 (s, 1H), 8.14 (s, 1H), 7.73-7.63 (m, 3H), 7.59 (t, J = 8.6 Hz, 1H), 7.38 (d, J = 7.4 Hz, 1H), 7.25 (d, J = 8.6 Hz, 1H), 7.11 (t, J = 6.0 Hz, 1H), 6.66 (d, J = 7.4 Hz, 1H), 5.62-5.36 (m, 1H), 4.44 (d, J = 5.9 Hz, 2H), 2.88-2.79 (m, 2H), 2.66-2.57 (m, 2H), 2.09-2.00 (m, 1H).

Compound 173. 1-(2-bromo-4,6-difluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.04 (s, 1H), 8.17 (s, 1H), 7.99 (s, 1H), 7.65 (d, J = 1.6 Hz, 2H), 7.55-7.48 ( m, 1H), 7.43-7.34 (m, 2H), 7.02 (t, J = 6.0 Hz, 1H), 6.65 (d, J = 7.4 Hz, 1H), 5.65-5.39 (m, 1H), 4.41 (d, J = 6.0 Hz, 2H), 2.89- 2.81 (m, 1H), 2.67-2.59 (m, 2H), 2.06-2.01 (m, 1H).

Compound 174. 3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-1,1-diethylurea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.03 (s, 1H), 8.09 (s, 1H), 7.65-7.57 (m, 2H), 7.36 (d, J = 7.4 Hz, 1H), 6.90 ( t, J = 5.9 Hz, 1H), 6.63 (d, J = 7.4 Hz, 1H), 5.63-5.39 (m, 1H), 4.34 (d, J = 5.8 Hz, 2H), 3.21 (q, J = 7.0 Hz, 4H), 2.88-2.79 (m, 1H), 2.68-2.55 (m, 2H), 2.08-1.98 (m, 1H), 1.04 (t, J = 7.0 Hz, 6 H).

Compound 175. 1-(2-bromo-4,6-dimethylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (500 MHz, DMSO- d ₆ ) δ 11.05 (s, 1H), 8.18 (s, 1H), 7.77 (s, 1H), 7.69-7.61 (m, 2H), 7.37 (d, J = 7.4 Hz, 1H), 7.31-7.28 (m, 1H), 7.06-7.03 (m, 1H), 6.81 (s, 1H), 6.65 (d, J = 7.4 Hz, 1H), 5.76-5.41 (m, 1H), 4.40 (d, J = 6.0 Hz, 2H) ), 2.93-2.84 (m, 1H), 2.68-2.57 (m, 2H), 2.25 (s, 3H), 2.19 (s, 3H), 2.07-2.01 (m, 1H).

Compound 176. 1-(3-bromo-4-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.02 (s, 1H), 9.03 (s, 1H), 8.13 (s, 1H), 7.71-7.58 (m, 3H), 7.38 (d, J = 7.4 Hz, 1H), 7.33-7.20 (m, 1H), 7.11-6.95 (m, 2H), 6.66 (d, J = 7.5 Hz, 1H), 5.61-5.41 (m, 1H), 4.42 (d, J = 5.9 Hz, 2H), 2.89-2.79 (m) , 1H), 2.67-2.58 (m, 2H), 2.10-1.99 (m, 1H).

Compound 177. 1-(3,4-difluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (500 MHz, DMSO - _d6 ) δ 11.04 (s, 1H), 8.96 (s, 1H), 8.13 (s, 1H), 7.90 (dd, J = 6.4, 2.6 Hz, 1H), 7.70- 7.60 (m, 2H), 7.38 (d, J = 7.4 Hz, 1H), 7.31-7.28 (m, 1H), 7.23 (t, J = 8.8 Hz, 1H), 7.00-6.95 (m, 1H), 6.66 (d, J = 7.4 Hz, 1H), 5.66- 5.35 (m, 1H), 4.41 (d, J = 6.0 Hz, 2H), 2.91-2.82 (m, 1H), 2.64-2.60 (m, 2H), 2.08-2.01 (m, 1H).

Compound 178. 1-((2-(2,6- Dioxopiperidine -3-day)-1-oxo-1,2- Dihydroisoquinoline -7-methyl)-3-(4-methoxyphenethyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.02 (s, 1H), 8.09 (s, 1H) _, 7.61 (s, 2H), 7.37 (d, J = 7.4 Hz, 1H), 7.11 (d, J = 8.3 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 6.65 (d, J = 7.5 Hz, 1H), 6.51 (t, J = 6.2 Hz, 1H), 5.96 (t, J = 5.8 Hz, 1H), 5.58-5.41 (m, 1H) , 4.32 (d, J = 6.0 Hz, 2H), 3.71 (s, 3H), 3.24-3.18 (m, 2H), 2.90-2.80 (m, 1H), 2.66-2.58 (m, 4H), 2.09-1.99 (m, 1H).

Compound 179. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-fluorophenyl)urea

^1H NMR (300 MHz, DMSO - _d6 ) δ 11.03 (s, 1H), 8.69 (s, 1H), 8.13 (s, 1H), 7.70-7.60 (m, 2H), 7.46-7.34 (m, 3H) ), 7.09-6.99 (m, 2H), 6.77 (t, J = 6.0 Hz, 1H), 6.66 (d, J = 7.4 Hz, 1H), 5.58-5.38 (m, 1H), 4.42 (d, J = 6.0 Hz, 2H), 2.90-2.78 (m , 1H), 2.67-2.56 (m, 2H), 2.06-1.97 (m, 1H).

Compound 180. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-methylcyclohexyl)urea

^1H NMR (300 MHz, _DMSO-d6 ) δ 11.04 (s, 1H), 8.07 (s, 1H), 7.65-7.56 (m, 2H), 7.37 (d, J = 7.4 Hz, 1H), 6.64 ( d, J = 7.5 Hz, 1H), 6.31 (t, J = 6.1 Hz, 1H), 5.83 (d, J = 8.0 Hz, 1H), 5.62-5.39 (m, 1H), 4.31 (d, J = 6.0 Hz, 2H), 2.90-2.80 (m, 1H), 2.66-2.57 (m, 2H), 2.09-1.98 (m, 1H), 1.85-1.75 (m, 2H), 1.69-1.58 (m, 2H), 1.52-1.39 (m, 1H), 1.34-1.22 (m, 1H), 1.15-1.01 (m, 2H), 1.01-0.89 (m , 2H) 0.88-0.81 (m, 3H).

Compound 181. 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-isopropylphenyl)urea

^1H NMR (300 MHz, DMSO -d6 ) δ 11.03 (s, 1H), 8.55 (s, 1H), 8.13 ₍ s, 1H), 7.70-7.61 (m, 2H), 7.38 (d, J = 7.4 Hz, 1H), 7.31 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 8.5 Hz, 2H), 6.73 (t, J = 6.0 Hz, 1H), 6.66 (d, J = 7.4 Hz, 1H), 5.60-5.38 (m, 1H), 4.42 (d, J = 5.9 Hz, 2H), 2.88-2.77 (m, 2H), 2.67-2.57 (m, 2H), 2.10-1.98 (m, 1H), 1.17 (s, 3H), 1.15 (s, 3H).

Compound 182. 1-(3,5-difluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.03 (s, 1H), 9.19 (s, 1H), 8.13 (s, 1H), 7.70-7.61 (m, 2H), 7.38 (d, J = 7.5 Hz, 1H), 7.19-7.10 (m, 2H), 7.10-7.03 (m, 1H), 6.73-6.63 (m, 2H), 5.60-5.38 (m, 1H), 4.42 (d, J = 5.9 Hz, 2H), 2.88-2.80 (m, 1H) , 2.64-2.58 (m, 2H), 2.08-1.98 (m, 1H).

Compound 183. 1-(4-bromo-2-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.04 (s, 1H), 8.60 (s, 1H), 8.19-8.11 (m, 2H), 7.67 (d, J = 1.9 Hz, 2H), 7.43- 7.36 (m, 2H), 7.24 (t, J = 5.7 Hz, 1H), 7.20-7.14 (m, 1H), 6.66 (d, J = 7.5 Hz, 1H), 5.57-5.42 (m, 1H), 4.45 (d, J = 5.9 Hz, 2H), 2.88- 2.80 (m, 1H), 2.67-2.58 (m, 3H), 2.08-1.98 (m, 1H).

Compound 184. 1-(4-chloro-2-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.03 (s, 1H), 8.61 (s, 1H), 8.14-8.07 (m, 2H), 7.70-7.62 (m, 2H), 7.51 (dd, J = 11.0, 2.3 Hz, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.27 (t, J = 9.1 Hz, 2H), 6.66 (d, J = 7.4 Hz, 1H), 5.60-5.38 (m, 1H), 4.45 (d, J = 5.8 Hz, 2H), 2.87-2.79 (m, 1H), 2.65-2.57 (m, 2H), 2.09-1.99 (m, 1H).

Compound 185. 1-(3-chloro-4-methylphenyl)-3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)ethyl)urea

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.04 (s, 1H), 8.57 (s, 1H), 8.16 (s, 1H), 7.75-7.69 (m, 1H), 7.65 (d, J = 8.2 Hz, 1H), 7.62 (d, J = 2.1 Hz, 1H), 7.39 (d, J = 7.4 Hz, 1H), 7.16 (d, J = 8.3 Hz, 1H), 7.08 (dd, J = 8.3, 2.1 Hz, 1H), 6.89 (d, J = 7.5 Hz, 1H), 6.66 (d, J = 7.4 Hz, 1H), 5.61-5.39 (m, 1H), 4.98-4.84 (m, 1H), 2.94-2.77 (m, 1H), 2.67-2.56 (m, 2H), 2.21 (s, 3H), 2.09-2.00 (m, 1H), 1.43 (d, J = 6.9 Hz, 3H).

Compound 186. 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)ethyl)urea

^1H NMR (300 MHz, DMSO - _d6 ) δ 11.05 (s, 1H), 8.98 (s, 1H), 8.17 (s, 1H), 8.05 (s, 1H), 7.76-7.70 (m, 1H), 7.65 (d, J = 8.2 Hz, 1H), 7.53 (d, J = 1.4 Hz, 2H), 7.39 (d, J = 7.4 Hz, 1H), 7.07 (d, J = 7.5 Hz, 1H), 6.66 (d, J = 7.4 Hz, 1H), 5.64- 5.33 (m, 1H), 5.00-4.87 (m, 1H), 2.93-2.77 (m, 1H), 2.68-2.55 (m, 2H), 2.09-2.00 (m, 1H), 1.44 (d, J = 6.9 Hz, 3H).

Compound 187. 1-(3-chloro-4-methoxyphenyl)-3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)ethyl)urea

^1H NMR (300 MHz, DMSO - _d6 ) δ 11.04 (s, 1H), 8.43 (s, 1H), 8.16 (s, 1H), 7.72 (dd, J = 8.1, 1.8 Hz, 1H), 7.65 ( d, J = 8.2 Hz, 1H), 7.59 (d, J = 2.5 Hz, 1H), 7.39 (d, J = 7.4 Hz, 1H), 7.15 (dd, J = 8.8, 2.6 Hz, 1H), 7.00 (d, J = 9.0 Hz, 1H), 6.86 -6.78 (m, 1H), 6.66 (d, J = 7.4 Hz, 1H), 5.49 (s, 1H), 4.97-4.85 (m, 1H), 3.77 (s, 3H), 2.94-2.78 (m, 1H), 2.69-2.56 (m, 2H), 2.10-2.00 (m, 1H), 1.42 (d, J = 6.9 Hz, 3H).

Compound 188. 3-(6-(aminomethyl)-1-oxoisoquinolin-2(1H)-yl)piperidine-2,6-dione hydrochloride

¹ H NMR (300 MHz, DMSO- d ₆ ) δ 11.08 (s,1H), 8.34 (s,1H), 8.31 (s,3H), 7.82 (d, J = 8.2 Hz, 1H), 7.74 (d, J = 8.2 Hz, 1H), 7.48 (d, J = 7.5 Hz, 1H), 6.71 (d, J = 7.5 Hz, 1H), 5.66-5.44 (m, 1H), 4.19 (s, 2H), 2.95-2.80 (m, 2H), 2.75-2.57 (m, 1H) , 2.11-1.99 (m, 1H).

Compound 189. 3-(7-(aminomethyl)-1-oxoisoquinolin-2(1H)-yl)piperidine-2,6-dione hydrochloride

^1H NMR (300 MHz, DMSO- d ₆ ) δ 11.07 (s,1H), 8.34 (s,3H), 7.82 (dd, J = 8.2, 1.9 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H), 7.47 (d, J = 7.4 Hz, 1H), 6.71 (d, J = 7.4 Hz, 1H), 5.68-5.42 (m, 1H), 4.24-4.13 (m, 2H), 2.96-2.81 (m, 1H), 2.74-2.56 (m, 2H), 2.10- 2.00 (m, 1H).

<Experimental Example 1. Evaluation of substrate protein decomposition activity for CRBN>

In order to confirm whether the compound of the present invention can specifically bind to CRBN (celebron) and inhibit the function of CRBN, the effect of the present compound on the decomposition activity of Ikaros/Aiolos protein (Chamberlain, P. P. et al., Nat Struct Mol Biol., 21(9), 803-809, 2014) or GSPT1 protein (Matyskiela, M. E. et al., Nature, 535(7611), 252-257, 2016), which are decomposed by CRBN protein when bound to thalidomide and its analogues, was investigated.

To evaluate the decomposition activity of the compound according to the present invention on Ikaros/Aiolos protein or GSPT1 protein, the following experiment was conducted.

OCI-LY3 cells were seeded at 5 × 10 ⁵ cells in a 12-well plate, and each compound was treated to each well at a determined concentration. Cell lysates were collected after 6 or 24 hours using TBSN buffer. Ikaros/Aiolos protein decomposition activity was evaluated using antibodies to Aiolos protein, and GSPT1 protein decomposition activity was evaluated using antibodies to GSPT1 protein by Western blot. To this end, equal amounts of proteins were loaded into each well of a 4-15% gradient gel, followed by electrophoresis, transfer of the proteins to a PVDF membrane, and binding with primary antibodies against each protein. Afterwards, HRP-conjugated secondary antibodies were bound, and development was performed using an HRP substrate.

As a result, as shown in Fig. 1, it was confirmed that the compound of the present invention promoted protein degradation of GSPT1 protein and Aiolos in the OCI-LY3 cell line when treated for 6 hours or 24 hours, respectively.

<Experimental Example 2. Cytotoxicity Test>

To confirm the effect of the compound of the present invention on cancer cells and normal cells, a cytotoxicity experiment was performed as follows.

Each cancer cell line (TMD8, KG-1, OCI-LY3, OCI-LY19, NALM6, Molt-4, HL-60, NB-4, MOLM-13, Tanoue, Caco-2) was seeded in a 96-well plate at 10,000 cells per well, and then treated with each of the exemplary compounds of the present invention and the comparative compounds in Table 1 below at predetermined concentrations. After 72 hours, the WST-1 reagent was added, and 1 hour later, the degree of cancer cell death was measured by measuring the absorbance at 450 nm using a spectramax spectrophotometer. The measured values were used to calculate the IC ₅₀ (μM) values using the graphpad prism program, and are shown in Tables 2 to 4.

structure Comparative compound 1 Comparative compound 2

compound
number IC ₅₀ (μM) compound
number IC ₅₀ (μM) compound
number IC ₅₀ (μM) TMD8 KG-1 TMD8 KG-1 TMD8 KG-1 Compound 1 +++ +++ Compound 51 +++ +++ Compound 91 ++ ++ Compound 2 +++ +++ Compound 52 +++ +++ Compound 92 +++ +++ Compound 4 ++ +++ Compound 53 +++ +++ Compound 93 +++ +++ Compound 5 ++ +++ Compound 54 + +++ Compound 94 +++ +++ Compound 6 +++ +++ Compound 55 + +++ Compound 95 +++ ++++ Compound 7 +++ +++ Compound 57 + +++ Compound 96 +++ +++ Compound 8 +++ +++ Compound 58 ++++ +++ Compound 97 +++ +++ Compound 9 +++ +++ Compound 59 + +++ Compound 98 +++ +++ Compound 10 ++ +++ Compound 60 ++ +++ Compound 99 +++ ++++ Compound 11 ++ ++ Compound 61 + +++ Compound 100 +++ ++++ Compound 12 ++ ++ Compound 62 +++ +++ Compound 101 + +++ Compound 13 + ++ Compound 63 ++ +++ Compound 102 +++ ++++ Compound 17 ++ ++ Compound 64 +++ +++ Compound 103 ++++ ++++ Compound 19 ++ +++ Compound 65 +++ +++ Compound 104 +++ ++++ Compound 20 ++ +++ Compound 66 + +++ Compound 105 +++ ++++ Compound 23 + +++ Compound 67 +++ +++ Compound 106 +++ ++++ Compound 26 ++ ++ Compound 68 +++ +++ Compound 107 +++ ++++ Compound 27 + ++ Compound 69 + +++ Compound 108 +++ ++++ Compound 28 + +++ Compound 70 +++ +++ Compound 109 +++ ++++ Compound 29 ++ ++ Compound 71 +++ +++ Compound 110 +++ ++++ Compound 31 + +++ Compound 72 +++ +++ Compound 111 ++ +++ Compound 32 + +++ Compound 73 +++ +++ Compound 112 ++ +++ Compound 33 ++ +++ Compound 75 ++ +++ Compound 113 ++ +++ Compound 34 +++ +++ Compound 76 ++ +++ Compound 114 +++ ++++ Compound 35 +++ +++ Compound 78 +++ +++ Compound 115 ++ +++ Compound 36 +++ +++ Compound 79 +++ +++ Compound 116 ++ +++ Compound 37 +++ +++ Compound 80 ++ +++ Compound 117 +++ ++++ Compound 40 +++ +++ Compound 81 +++ +++ Compound 118 +++ ++++ Compound 41 +++ +++ Compound 82 ++ +++ Compound 119 +++ ++++ Compound 42 +++ +++ Compound 83 ++ +++ Compound 120 ++ +++ Compound 43 ++ +++ Compound 84 ++ +++ Compound 121 +++ ++++ Compound 44 +++ +++ Compound 85 + +++ Compound 122 +++ ++++ Compound 45 +++ +++ Compound 86 + +++ Compound 123 +++ ++++ Compound 46 +++ +++ Compound 87 ++ +++ Compound 124 +++ +++ Compound 48 ++ +++ Compound 88 ++ +++ Compound 125 +++ ++++ Compound 49 ++ ++ Compound 89 ++ +++ Comparative compound 1 ++ ++ Compound 50 + +++ Compound 90 + +++ Comparative compound 2 + + * IC ₅₀ value
++++: 0.0001~0.01μM, +++: 0.01~1μM, ++: 1~10μM, +: 10~50μM

compound
number IC ₅₀ (μM) compound
number IC ₅₀ (μM) TMD8 KG-1 TMD8 KG-1 Compound 142 +++ +++ Compound 161 + +++ Compound 143 ++++ ++++ Compound 162 + ++ Compound 144 +++ +++ Compound 163 + ++ Compound 145 + ++ Compound 164 + +++ Compound 146 + ++ Compound 165 + +++ Compound 147 + ++ Compound 166 ++ +++ Compound 148 + + Compound 171 + + Compound 149 +++ ++ Compound 172 + ++ Compound 150 + ++ Compound 179 ++ ++ Compound 151 + ++ Compound 180 + + Compound 152 + ++ Compound 181 + ++ Compound 153 + + Compound 182 + + Compound 154 + +++ Compound 183 + + Compound 155 + + Compound 184 + + Compound 156 + + Compound 185 + +++ Compound 157 + ++ Compound 186 + + Compound 160 ++ ++ Compound 187 ++ ++ * IC ₅₀ value
++++: 0.0001~0.01μM, +++: 0.01~1μM, ++: 1~10μM, +: 10~50μM

cancer cell line IC ₅₀ (μM) Compound 1 Compound 2 OCI-LY3 +++ +++ OCI-LY19 ++++ ++++ NAML6 +++ ++++ Molt-4 ++++ ++++ HL-60 ++++ ++++ NB-4 ++++ ++++ MOLM-13 +++ ++++ Tanoue +++ +++ Caco-2 +++ +++ * IC ₅₀ value
++++: 0.0001~0.01μM, +++: 0.01~1μM, ++: 1~10μM, +: 10~50μM

As shown in Tables 2 and 3, it was found that the compounds of the present invention had sufficient cytotoxicity on cancer cells, and in particular, unlike comparative compounds 1 and 2, it was confirmed that the compounds of the present invention in which a urea derivative was substituted had better cytotoxicity on cancer cells.

In addition, as shown in Table 2, it was confirmed that in the case of the triazine derivative compound in which X is N in the chemical formula 1 of the present invention, the cytotoxic activity against cancer cells was more excellent than in the case of the pyridine derivative compound in which X is C in the chemical formula 1 of the present invention, as shown in Table 3.

Next, looking at Table 4, compounds 1 and 2 of the present invention exhibited cytotoxicity against various types of cancer cells, and although not shown in Table 4, the remaining compounds, except for compounds 1 and 2 of the present invention, also exhibited IC ₅₀ values of 0.0001 to 0.1 μM against 9 types of cancer cells, confirming that the compounds of the present invention have excellent cytotoxicity against cancer cells.

<Example 1. Preparation of a mountain ash>

2 g of the compound of the present invention 1 (1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea) and 1 g of lactose were mixed and filled into an airtight pouch to prepare a powder.

<Example 2. Preparation of tablets>

100 mg of the compound of the present invention 1(1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea), 100 mg of microcrystalline cellulose, 60 mg of lactose hydrate, 20 mg of low-substituted hydroxypropyl cellulose, and 2 mg of magnesium stearate were mixed and then compressed into tablets according to a conventional tablet manufacturing method.

<Example 3. Preparation of capsules>

100 mg of the compound of the present invention 1(1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea), 100 mg of microcrystalline cellulose, 60 mg of lactose hydrate, 20 mg of low-substituted hydroxypropyl cellulose, and 2 mg of magnesium stearate were mixed, and then the above ingredients were mixed according to a conventional capsule manufacturing method and filled into a gelatin capsule to manufacture a capsule.

<Example 4. Preparation of the drug>

90 mg of the compound of the present invention 1(1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea), 5 mg of glutinous rice starch, 5 mg of purified water, and a small amount of dextrin, maltodextrin, corn starch, and microcrystalline cellulose (MCC) as additives that inhibit hygroscopicity were mixed, and then a 100 mg pill was made according to a conventional method.

< Example of preparation 5. Preparation of injection>

10 mg of the compound of the present invention 1(1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea), an appropriate amount of sterile distilled water for injection, and an appropriate amount of a pH adjuster were mixed, and then prepared with the above ingredient contents per 1 ampoule (2 ml) according to a method for preparing a conventional injection.

Claims (8)

A compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof:
[Chemical Formula 1]

In the above chemical formula 1,
X is all nitrogen (N) or all carbon (C);
R ₁ is selected from the group consisting of -(CH ₂ ) _m NH(CO)NHR ₄ , -(CH ₂ ) _m NH(CS)NHR ₄ or -(CH ₂ ) _m NH(CO)R ₄ ;
R ₂ is hydrogen, deuterium or C ₁ -C ₆ alkyl;
R ₃ is hydrogen, C ₁ -C ₆ alkyl, -CH ₂ OCOR ₅ , -CH ₂ OCOOR ₅ , -CH ₂ OCONR ₆ R ₇ or is substituted in the group consisting of;
R ₄ is substituted with a substituent selected from the group consisting of C ₁ -C ₁₀ alkyl, substituted or unsubstituted C ₄ -C ₁₀ cycloalkyl, substituted or unsubstituted C ₆ -C ₁₀ aryl, substituted or unsubstituted C ₆ -C ₁₀ aryl C ₁ -C ₂ alkyl or C ₄ -C ₁₀ heteroaryl C ₁ -C ₂ alkyl,
At this time, the substituted cycloalkyl, aryl, arylalkyl, or heteroarylalkyl is substituted with a substituent selected from the group consisting of hydrogen, halogen, hydroxy, CF ₃ , S-CF ₃ , C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₃ -C ₆ cycloalkyl, or C ₆ -C ₁₀ aryl;
R ₅ is substituted with a substituent selected from the group consisting of hydrogen, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ heterocycloalkyl, or -(CH ₂ CH ₂ O) _n CH ₃ ,
At this time, the substituted alkyl, cycloalkyl or heterocycloalkyl is substituted with a substituent selected from the group consisting of hydrogen, hydroxy, amino, acetamino, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;
R ₆ and R ₇ are each independently substituted with a substituent selected from the group consisting of hydrogen, hydroxy, amino, acetamino, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, or substituted or unsubstituted C ₃ -C ₆ heterocycloalkyl,
At this time, the substituted alkyl, alkoxy, cycloalkyl or heterocycloalkyl is substituted with a substituent selected from the group consisting of hydrogen, hydroxy, amino, acetamino, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;
R ₈ is substituted with a substituent selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl, -(CH ₂ ) _m -imidazole, an amino acid residue or a derivative thereof;
n is an integer from 1 to 5; and
m is an integer from 1 to 5; In the first paragraph,
In the above chemical formula 1,
X is all nitrogen (N) or all carbon (C);
R ₁ is selected from the group consisting of -(CH ₂ ) _m NH(CO)NHR ₄ , or -(CH ₂ ) _m NH(CS)NHR ₄ ;
R ₂ is hydrogen or deuterium;
R ₃ is hydrogen or C ₁ -C ₆ alkyl, -CH ₂ OCOR ₅ , -CH ₂ OCOOR ₅ , -CH ₂ OCONR ₆ R ₇ or is substituted in the group consisting of;
R ₄ is C ₁ -C ₁₀ alkyl, substituted or unsubstituted C ₄ -C ₁₀ cycloalkyl, substituted or unsubstituted substituted with a substituent selected from the group consisting of C ₆ -C ₁₀ aryl, substituted or unsubstituted C ₆ -C ₁₀ aryl C ₁ -C ₂ alkyl, or C ₄ -C ₁₀ heteroaryl C ₁ -C ₂ alkyl,
At this time, the substituted cycloalkyl, aryl, arylalkyl, or heteroarylalkyl is substituted with a substituent selected from the group consisting of hydrogen, halogen, hydroxy, CF ₃ , S-CF ₃ , C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₃ -C ₆ cycloalkyl, or C ₆ -C ₁₀ aryl;
R ₅ is substituted with a substituent selected from the group consisting of hydrogen, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, substituted or unsubstituted C ₃ -C ₆ heterocycloalkyl, or -(CH ₂ CH ₂ O) _n CH ₃ ,
At this time, the substituted alkyl, cycloalkyl or heterocycloalkyl is substituted with a substituent selected from the group consisting of hydrogen, hydroxy, amino, acetamino, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;
R ₆ and R ₇ are each independently substituted with a substituent selected from the group consisting of hydrogen, hydroxy, amino, acetamino, substituted or unsubstituted C ₁ -C ₆ alkyl, substituted or unsubstituted C ₁ -C ₆ alkoxy, substituted or unsubstituted C ₃ -C ₆ cycloalkyl, or substituted or unsubstituted C ₃ -C ₆ heterocycloalkyl,
At this time, the substituted alkyl, alkoxy, cycloalkyl or heterocycloalkyl is substituted with a substituent selected from the group consisting of hydrogen, hydroxy, amino, acetamino, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy;
R ₈ is substituted with a substituent selected from the group consisting of hydrogen, C ₁ -C ₆ alkyl or -(CH ₂ ) _m -imidazole;
n is an integer from 1 to 3; and
m is an integer from 1 to 3;
A compound characterized by: or a pharmaceutically acceptable salt thereof. A compound or a pharmaceutically acceptable salt thereof, characterized in that it is selected from the group consisting of the following compounds.
1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 1);
1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 2);
1-(3-chloro-4-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-5-yl)methyl)urea (Compound 3);
1-(3-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 4);
1-(4-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 5);
1-(3,4-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 6);
1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 7);
1-(3-chloro-4-methoxyphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 8);
3-Chloro-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)benzamide (Compound 9);
3-Chloro-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-4-methylbenzamide (Compound 10);
1-(3-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)thiourea (Compound 11);
2-(3-chlorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 12);
tert-Butyl((2R)-1-(((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (Compound 13);
(2R)-2-Amino-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-phenylpropanamide hydrochloride (Compound 14);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methoxyphenyl)urea (Compound 15);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methoxyphenylethyl)urea (Compound 16);
2-(2,4-Dichlorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 17);
2-(4-Bromophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 18);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(m-tolyl)urea (Compound 19);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methylbenzyl)urea (Compound 20);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(3-methoxybenzyl)urea (Compound 21);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(p-tolyl)urea (Compound 22);
1-(4-chlorobenzyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 23);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-urea (Compound 24);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-phenylurea (Compound 25);
2-(3-Bromophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 26);
2-(4-chlorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 27);
2-(4-chloro-2-fluorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-7-yl)methyl)acetamide (Compound 28);
2-(3,4-difluorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 29);
2-(3,5-difluorophenyl)-N-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)acetamide (Compound 30);
1-(2-Bromo-4,6-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea (Compound 31);
1-(2-Bromo-4,6-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea (Compound 32);
1-(2-chloro-4-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 33);
1-(2,3-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 34);
1-(3-chloro-4-methoxyphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-6-yl)methyl)urea (Compound 35);
1-(4-chlorobenzyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 36);
1-(4-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 37);
1-(2,6-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 38);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(m-tolyl)urea (Compound 39);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-urea (Compound 40);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(p-tolyl)urea (Compound 41);
1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 42);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-methoxyphenyl)urea (Compound 43);
1-(3,4-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 44);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(trifluoromethyl)phenyl)urea (Compound 45);
1-(3,5-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 46);
1-(2,6-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 47);
1-(2-Bromo-4,6-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 48);
1-(2-Bromo-4,6-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 49);
1-(2-chloro-4-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 50);
1-(2,3-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 51);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(trifluoromethyl)phenyl)urea (Compound 52);
1-(3,4-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 53);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-methoxyphenylethyl)urea (Compound 54);
3-((3-(2,6-deoxypiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)diethylurea (Compound 55);
3-((3-(2,6-deoxypiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)diethylurea (Compound 56);
1-(4-(tert-butyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 57);
1-(4-(tert-butyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 58);
1-(Benzo[d][1,3]dioxol-5-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-7-yl)methyl)urea (Compound 59);
1-(Benzo[d][1,3]dioxol-5-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)methyl)urea (Compound 60);
1-(Benzo[d]thiazol-6-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea (Compound 61);
1-(3-chloro-4-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-6-yl)methyl)urea (Compound 62);
1-(4-Bromo-2-chloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 63);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-fluoro-3-methylphenyl)urea (Compound 64);
1-(3,4-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 65);
1-(2,4-Dichloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea (Compound 66);
1-(2,4-Dichloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)methyl)urea (Compound 67);
1-(4-Bromo-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)methyl)urea (Compound 68);
1-(4-Bromo-3-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 69);
1-(4-Bromo-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 70);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(trifluoromethyl)phenyl)urea (Compound 71);
1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 72);
1-(3-chloro-4-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 73);
1-(4-Bromo-2-chloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 74);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-fluoro-3-methylphenyl)urea (Compound 75);
1-(3,4-dimethylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 76);
1-(2,4-Dichloro-6-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-7-yl)methyl)urea (Compound 77);
1-(3-Bromo-4-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 78);
1-(4-Bromo-3-methylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 79);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(4-(trifluoromethyl)phenyl)urea (Compound 80);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-((trifluoromethyl)thio)phenyl)urea (Compound 81);
1-(3,4-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 82);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(3,4,5-trifluorophenyl)urea (Compound 83);
1-(2,4-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 84);
1-(3,4-difluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 85);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(3,4,5-trifluorophenyl)urea (Compound 86);
1-(2,4-Dichlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)urea (Compound 87);
1-(4-Bromo-3-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]-7-yl)methyl)urea (Compound 88);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)methyl)-3-(trifluoromethyl)phenyl)urea (Compound 89);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-phenylurea (Compound 90);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-isobutylurea (Compound 91);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(4-methylcyclohexyl)urea (Compound 92);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-urea (Compound 93);
1-(4-chloro-2-fluorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 94);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-urea (Compound 95);
1-(4-Cyclopropylphenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 96);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(trifluoromethyl)phenyl)urea (Compound 97);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-isobutylphenyl)urea (Compound 98);
1-([1,1'-Biphenyl]-3-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 99);
1-(3-(tert-butyl)phenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 100);
1-([1,1'-Biphenyl]-4-yl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 101);
1-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)-3-(5,6,7,8-tetrahydronaphthalen-2-yl)urea (Compound 102);
1-(4-(tert-butyl)-3-chlorophenyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 103);
(2,3-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 104);
1-(3-chloro-4-methylphenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)ethyl)urea (Compound 105);
1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 106);
1-(4-(tert-butyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 107);
1-([1,1'-Biphenyl]-3-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)ethyl)urea (Compound 108);
1-(3-(tert-butyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 109);
1-(4-(tert-butyl)-3-chlorophenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 110);
1-(4-(tert-butyl)-3-chlorophenyl)-3-(2-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)propan-2-yl)urea (Compound 111);
1-(4-(tert-butyl)benzyl)-3-((3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)methyl)urea (Compound 112);
1-(4-(tert-butyl)benzyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 113);
1-(3-Bromo-4-(tert-butyl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)ethyl)urea (Compound 114);
1-(2-(4-chlorophenyl)propan-2-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d]1,2,3]triazin-6-yl)ethyl)urea (Compound 115);
1-(1-(4-chlorophenyl)ethyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 116);
1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(5,6,7,8-tetrahydronaphthalen-2-yl)urea (Compound 117);
1-(2,3-Dihydro-1H-indene-5-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 118);
1-(4-chloro-3-methylphenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]]triazin-6-yl)ethyl)urea (Compound 119);
1-(3-(tert-butyl)-4-chlorophenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 120);
1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(3'-methyl-[1,1'-biphenyl]-3-yl)urea (Compound 121);
1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(9H-fluoren-3-yl)urea (Compound 122);
1-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)-3-(2'-methyl-[1,1'-biphenyl]-3-yl)urea (Compound 123);
1-(3-(Benzo[d]thiazol-2-yl)phenyl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 124);
1-(4'-Chloro-[1,1'-biphenyl]-3-yl)-3-(1-(3-(2,6-dioxopiperidin-3-yl)dihydrobenzo[d][1,2,3]triazin-6-yl)ethyl)urea (Compound 125);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methyl acetate (Compound 126);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylisobutyrate (Compound 127);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylcyclopentanecarboxylate (Compound 128);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methyl prolanate (Compound 129);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methyl methyl carbonate (Compound 130);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methyl methyl carbonate (Compound 131);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylpiperidin-4-ylcarbonate (Compound 132);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2-(2-methoxyethoxy)ethoxy)ethyl)carbonate (Compound 133);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2-acetamidoethyl)carbamate (Compound 134);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2-((R)-2-amino-3-methylbutanamido)ethyl)carbamate (Compound 135);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2,6-dioxopiperidin-1-yl)methyl(2-aminoethyl)carbamate (Compound 136);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazine-3(4H)-(2,6-dioxopiperidin-1-yl)methylvalinate (Compound 137);
(3-(6-(1-(3-(4-(tert-butyl)-3-chlorophenyl)ureido)ethyl)-4-oxobenzo[d][1,2,3]triazin-3(4H)-pyridin-2-yl)-2,6-dioxopiperidin-1-yl)methylhistine (Compound 138);
1-(3-chloro-4-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 142);
1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 143);
1-(3-chloro-4-methoxyphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 144);
1-(3-chloro-4-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-6-yl)methyl)urea (Compound 145);
1-(4-chloro-3-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-6-yl)methyl)urea (Compound 146);
1-(3,4-Dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 147);
1-(3,5-Dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 148);
1-(2,3-Dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 149);
1-(2-chloro-4-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 150);
1-(4-Bromo-3-(trifluoromethyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 151);
1-(4-(tert-butyl)phenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 152);
1-(3-chlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 153);
1-(4-chlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 154);
1-(4-Bromo-2-chloro-6-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 155);
1-(4-Bromo-2-chloro-6-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroxyisoquinolin-7-yl)methyl)urea (Compound 156);
1-(4-chlorobenzyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 157);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-fluorophenethyl)urea (Compound 158);
1-(2,6-Dichlorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 159);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(m-tolyl)urea (Compound 160);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-fluoro-3-methylphenyl)urea (Compound 161);
1-(3,4-dimethylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 162);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-((trifluoromethyl)thio)phenyl)urea (Compound 163);
1-(Benzo[d][1,3]dioxol-5-ylmethyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 164);
1-(Benzo[d]thiazol-6-yl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 165);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(p-tolyl)urea (Compound 166);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(3,4,5-trifluorophenyl)urea (Compound 167);
1-(4-Bromo-3-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 168);
1-(3-chloro-4-methoxyphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 169);
1-(3-chloro-4-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 170);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-methoxyphenyl)urea (Compound 171);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(3-fluoro-4-(trifluoromethyl)phenyl)urea (Compound 172);
1-(2-Bromo-4,6-difluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 173);
3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-1,1-diethylurea (Compound 174);
1-(2-Bromo-4,6-dimethylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 175);
1-(3-Bromo-4-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 176);
1-(3,4-difluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 177);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-methoxyphenethyl)urea (Compound 178);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-fluorophenyl)urea (Compound 179);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-methylcyclohexyl)urea (Compound 180);
1-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)-3-(4-isopropylphenyl)urea (Compound 181);
1-(3,5-Difluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 182);
1-(4-Bromo-2-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 183);
1-(4-chloro-2-fluorophenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)methyl)urea (Compound 184);
1-(3-chloro-4-methylphenyl)-3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)ethyl)urea (Compound 185);
1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)ethyl)urea (Compound 186);
1-(3-chloro-4-methoxyphenyl)-3-(1-(2-(2,6-dioxopiperidin-3-yl)-1-oxo-1,2-dihydroisoquinolin-7-yl)ethyl)urea (Compound 187). In the second paragraph,
In the above chemical formula 1,
A compound or a pharmaceutically acceptable salt thereof, wherein all Xs are nitrogen (N). delete (a) a step of reacting a compound represented by the following chemical formula 2 with a compound represented by the following chemical formula 3 to produce a compound represented by the following chemical formula 4; and
(b) A method for producing a compound represented by the following chemical formula 5 by reacting a compound represented by the following chemical formula 4 with NaNO ₂ :
[Chemical formula 2]

[Chemical Formula 3]

[Chemical Formula 4]

[Chemical Formula 5]

In the above chemical formula 2,
R ₁ is substituted and selected from the group consisting of -(CH ₂ ) _m NH(CO)NHR ₄ , -(CH ₂ ) _m NH(CS)NHR ₄ and -(CH ₂ ) _m NH(CO)R ₄ ;
R ₄ is substituted with one or more substituents selected from the group consisting of C ₁ -C ₁₀ alkyl, substituted or unsubstituted C ₄ -C ₁₀ cycloalkyl, substituted or unsubstituted C ₆ -C ₁₀ aryl, substituted or unsubstituted C ₆ -C ₁₀ aryl C ₁ -C ₂ alkyl or C ₄ -C ₁₀ heteroaryl C ₁ -C ₂ alkyl;
n is an integer from 1 to 5; and
m is an integer from 1 to 3; A pharmaceutical composition for preventing or treating leprosy, chronic graft-versus-host disease, inflammatory disease or cancer, comprising a compound of any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof as an active ingredient. In Article 7,
The above cancer is selected from the group consisting of breast cancer, colon cancer, lung cancer, small cell lung cancer, stomach cancer, liver cancer, blood cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, anal cancer, colon cancer, breast cancer, fallopian tube carcinoma, endometrial carcinoma, cervical cancer, vaginal cancer, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvic carcinoma, CNS tumor, primary CNS lymphoma, spinal cord tumor, brainstem glioma, and pituitary adenoma. A pharmaceutical composition for preventing or treating leprosy, chronic graft-versus-host disease, inflammatory diseases, or cancer.