IMIDAZOPYRIDINE COMPOUNDS AS PAD INHIBITORS Russian patent published in 2022 - IPC C07D471/04 A61K31/4184 A61P35/00 A61P37/00 A61P17/00 

FIELD: organic chemistry; pharmacology.

SUBSTANCE: group of inventions relates to the field of organic chemistry and pharmacology; it is aimed at the treatment of disorders mediated by PAD4. Heterocyclic compounds of the formula (I) are disclosed, where X is selected from O or S; Z is N; A is CR₁; B is CR₂; D is CR₃; R₁, R₂, R₃, and R₄ are independently selected from hydrogen, C_1-6alkyl, C_3-6cycloalkyl, or C₆aryl, where C_1-6alkyl is optionally substituted with C_1-6alkoxy; R₁₁ and R₁₂ can be taken together to form a 5-10-element monocyclic or bicyclic saturated heterocyclic ring, optionally with 1-3 heteroatoms selected from N, S, or O, where the 5-10-element monocyclic or bicyclic saturated heterocyclic ring is optionally substituted with substitutes selected from amino or -NH(CO)CH=CH-CH₂-N(CH₃)₂; and R₁₃ is selected from 6-element monocyclic aryl and 5-10-element monocyclic or bicyclic heteroaryl with 1-3 heteroatoms selected from N, S, or O, where 6-element monocyclic aryl and 5-10-element monocyclic or bicyclic heteroaryl are optionally substituted with 1-5 substitutes selected from halogen, C_1-6alkyl, C_1-6alkoxy, or C₆aryl, where C_1-6alkyl and C₆aryl are optionally substituted with one or several groups selected from C_1-6alkyl, C_1-6halogenalkyl, C_1-6alkoxy, C_3-6cycloalkyl, C₆aryl, 5-6-element heteroaryl containing 1-3 heteroatoms selected from N, S, and O, 5-6-element heterocyclyl containing 1 or 2 heteroatoms selected from N, S, and O, oxo, halogen and hydroxyl, where C₆aryl, heteroaryl, and heterocyclyl are optionally substituted with one or more groups selected from C_1-6alkyl, C_1-6alkoxy, oxo, halogen, -CH₂OH, and cyano. In addition, heterocyclic compounds of formulas (II) and (III), methods for the production of heterocyclic compounds of formulas (I), (II), and (III), a pharmaceutical composition with PAD4 inhibitor activity based on the above-mentioned compounds, a method for inhibition of PAD4 in a cell, as well as methods for the treatment of conditions mediated by PAD4, and the use of compounds of formulas (I), (II), and (III) for the treatment of conditions mediated by PAD4 are disclosed.

EFFECT: group of inventions provides effective inhibition of PAD4, which may be suitable for the treatment of various disorders, including rheumatoid arthritis, vasculitis, systemic lupus erythematosus, cutaneous lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, multiple sclerosis, and psoriasis.

25 cl, 1 tbl, 2 ex