BICYCLIC DIHYDROPYRIMIDINECARBOXAMIDE DERIVATIVES AS RHO-KINASE INHIBITORS Russian patent published in 2022 - IPC C07D487/04 A61K31/519 A61P11/00 A61P11/06 A61P37/00 

FIELD: biotechnology.

SUBSTANCE: invention relates to a compound of the formula (Ia) in the form of individual enantiomer, diastereoisomer, or a mixture thereof in any proportion, as well as its pharmaceutically acceptable salts, which have inhibitory activity relatively to isoforms ROCK-I and ROCK-II of super-spiral Rho-associated protein kinase (hereinafter – ROCK); they can be used in the prevention and/or treatment of lung diseases. In the formula (Ia), R₃ and R₄ are independently selected from a group consisting of -H, CN, halogen, -NR₅R₆, (C₁-C₆)alkyl, etc.; R₅ and R₆, in each case, are independently selected from a group consisting of H, (C₁-C₆)alkyl, (C₁-C₆)aminoalkyl, (C₁-C₆)alkoxy-(C₁C₆)alkyl, (C₃-C₆)heterocycloalkyl-(C₁-C₆)alkyl, etc.; or R₅ and R₆, together with a nitrogen atom, to which they are attached, form 4-6-element heterocyclic radical, where at least one additional ring carbon atom in the mentioned heterocyclic radical can be substituted with at least one heteroatom selected from N, S, or O; R₁ is selected from a group consisting of (C₁-C₆)alkyl, (C₃-C₁₀)cycloalkyl, aryl(C₁-C₆)alkyl, aryl; R₂ is selected from (C₁-C₆)alkyl, (C₃-C₁₀)cycloalkyl, (C₁-C₆)alkoxy-(C₁-C₆)alkyl; A is bicyclic heteroaryl selected from 1H-indazole-5-yl, 6-fluor-1H-indazole-5-yl, isoquinoline-6-yl, thieno[2,3-c]pyridine-2-yl, thieno[3,2-c]pyridine-2-yl, [1,2,4]triazolo[4,3-a]pyridine-7-yl, 1,6-naphthyridine-2-yl. The invention also relates to specific compounds and a pharmaceutical composition having the specified activity.

EFFECT: obtaining compounds and a pharmaceutical composition having inhibitory activity relatively to ROCK isoforms.

(Ia)

7 cl, 29 tbl, 138 ex