NITROGEN-CONTAINING HETEROCYCLIC DERIVATIVES USEFUL AS PLASMA KALLIKREIN INHIBITOR Russian patent published in 2020 - IPC C07D401/14 C07D403/14 C07D413/14 C07D417/14 C07D417/06 C07D471/04 A61K31/437 A61K31/4725 A61P3/10 A61P43/00 

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to a heterocyclic compound of formula (I), isomers thereof, stereoisomers and pharmaceutically acceptable salts thereof, where B is fused 6,5- or 6,6-heteroaromatic bicyclic ring containing N and optionally 1–2 nitrogen atoms, which is optionally substituted with 1–2 substitutes selected from alkyl, alkoxy, halogen and NR8R9; where, when B is fused 6,5-heteroaromatic bicyclic ring, it is linked to -CONH-CH₂- through its 6-member ring component; W, X, Y and Z are independently selected from C, N and S, whereby ring is pyrazole, pyrrole or thiazole; where R5, R6 and R7 are absent or are selected from H, alkyl, halogen, aryl, heteroaryl, -NR8R9, CN, COOR8, CONR8R9, -NR8COR9, CF₃ and R16; where at least one of R5, R6 and R7 is present and is selected from alkyl, halogen, aryl, heteroaryl, -NR8R9, CN, COOR8, CONR8R9, -NR8COR9, CF₃ and R16; A is selected from aryl and heteroaryl; R8 and R9 are selected from H and alkyl; R16 is carbon-containing 3–6-member monocyclic ring which can be aromatic, saturated or unsaturated, optionally containing 2 heteroatoms selected from N and O, where ring R16, in its turn, is optionally substituted with 2 substitutes selected from alkyl and oxo; alkyl-linear saturated (C₁-C₆) hydrocarbon or branched saturated (C₃-C₆) hydrocarbon; alkyl is optionally substituted with 1–2 substitutes selected from (C₁-C₆)alkoxy, OH, CF₃ and fluorine; alkoxy - linear O-linked (C₁-C₆) hydrocarbon or branched O-linked (C₃-C₆) hydrocarbon; alkoxy is optionally substituted with one CF₃; aryl is phenyl; aryl is optionally substituted with 1 substituent independently selected from ethylenedioxy, -(CH₂)_0-3-O-heteroaryl, -(CH₂)_1-3-heteroaryl and -(CH₂)_1-3-NR14R15; heteroaryl is 5- or 6-member monocyclic aromatic ring containing, when possible, 1–3 ring elements independently selected from N, NR8, S and O; heteroaryl is optionally substituted with 1–2 substitutes selected from alkyl, alkoxy, halogen, CN, aryl, -CONR10R11 and -NR10R11; R10 and R11 are selected from H and alkyl or R10 and R11 together with the nitrogen atom to which they are attached form carbon-containing 5-member heterocyclic ring which can be saturated or unsaturated with 2 double bonds and which is optionally substituted with 1–2 substitutes selected from alkyl and F; R14 and R15 together with the nitrogen atom to which they are attached form carbon-containing 5- or 6-member heterocyclic ring which is unsaturated with 2 double bonds and optionally oxo-substituted; or a compound of formula (I) is (1-aminoisoquinolin-6-ylmethyl)-amide of 3-cyclopropyl-1-(6-phenoxypyridin-3-ylmethyl)-1H-pyrazole-4-carboxylic acid, isomers thereof, stereoisomers and its pharmaceutically acceptable salts with exception of 1-benzyl-5-chloro-3-methyl-N - [(4-methylquinazolin-2-yl)] - 1H-prazole-4-carboxamide. Invention also relates to a pharmaceutical composition based on the compound of formula (I), use thereof and a method of treating diseases which are organically associated with plasma kallikrein activity.

EFFECT: technical result is obtaining novel heterocyclic compounds having useful biological properties.

31 cl, 17 tbl, 129 ex