HETEROCYCLIC COMPOUNDS AS PAD INHIBITORS Russian patent published in 2022 - IPC C07D471/04 C07D498/04 A61K31/4188 A61K31/4985 

FIELD: chemistry.

SUBSTANCE: invention relates to a compound by the formula (I), stereoisomers thereof and pharmaceutically acceptable salts thereof, wherein X represents O or S; Y is selected from O or N; Z is N; A represents CR₁; B represents CR₂; n equals 0 or 1; R₁ and R₂ are independently selected from hydrogen; R₃ is absent when Y is O or N when Y is selected from the group consisting of hydrogen, C_1-6alkyl, C_3-6cycloalkyl, C(O)C_1-6alkyl, SO₂C_1-6alkyl, SO₂C_3-6cycloalkyl and SO₂C₆aryl, wherein SO₂C₆aryl and SO₂C_1-6alkyl are optionally substituted with C_1-6alkoxy, halogen and C₆aryl; R₁₀ and R₁₁ are taken together, forming a 5-6-membered monocyclic saturated heterocyclic ring, wherein the 5-6-membered monocyclic saturated heterocyclic ring is optionally substituted with substituents selected from the group consisting of amino, C₁alkylamino, and -NHC(O)CH=CHCH₂N(CH₃)₂; R₁₂, R₁₃, R₁₄, and R₁₅ are independently selected from the group consisting of hydrogen and C_1-6alkyl, R₁₆ is selected from a 9-membered bicyclic heteroaryl containing 1 to 2 heteroatoms selected from N or S, wherein the 9-membered bicyclic heteroaryl is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C_1-6alkyl, C_1-6alkoxy, C_1-6alkyl-C₆aryl, C_2-6alkenyl-C₆aryl, C_1-6alkyl-C_3-5heterocyclyl, wherein the heterocyclyl comprises one heteroatom selected from a nitrogen or oxygen atom (oxetan, tetrahydropyran, piperidine), C_3-5heteroaryl, and C_1-6alkyl-C_3-5heteroaryl, wherein heteroaryl comprises from 1 to 2 heteroatoms in the ring, selected from a nitrogen or sulpur atom (pyridine, pyrimidine, pyridazine, and thiazole), and wherein C_1-6alkyl, C_1-6alkyl-C₆aryl, C_3-5heteroaryl, C_1-6alkyl-C_3-5heteroaryl, and C_1-6alkyl-C_3-5heterocyclyl are optionally substituted with one or several groups selected from hydrogen, C_1-6alkyl, C_1-6alkoxy, C_3-8cycloalkyl, halogen, hydroxyl, -CH₂OH, and -COOH. The invention also relates to compounds by the formula (II) and compounds by the formula (III).

EFFECT: compounds represented by formulas (I), (II), (III) are intended for inhibiting the enzymatic activity of PAD4 in a cell; compound by the formula (I), formula (II), and formula (III) is intended for application for treating a PAD4-mediated condition selected from rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, and psoriasis.

19 cl, 1 tbl, 88 ex