ISOQUINOLINE COMPOUNDS, METHOD FOR PRODUCTION THEREOF AND PHARMACEUTICAL COMPOSITIONS THEREWITH Russian patent published in 2019 - IPC C07D217/02 C07D401/10 C07D403/10 C07D405/06 C07D405/10 A61K31/472 A61K31/4725 A61P1/16 A61P3/10 A61P5/50 A61P7/02 A61P9/12 A61P11/00 A61P15/10 A61P35/00 A61P37/00 

FIELD: organic chemistry.

SUBSTANCE: invention relates to the field of organic chemistry, namely to new isoquinoline derivatives of formula (I), where X: -C(=O), -CH(OH)- or -CH₂-; Ri₁ represents H or a hydroxyl group, it is assumed that the compound of formula (I), where Ri₁ is the OH group, may be represented by its tautomeric form, as indicated in paragraph 1; Ri₂ and Ri₃ may be the same or different, represent a hydrogen atom, (C₁-C₆)an alkyl group or a halogen atom; Ri₆, Ri₇ and Ri₈ represent a hydrogen atom; Ra₁ and Ra₅ may be the same or different, represent a hydrogen atom or a halogen atom, -O(C₁-C₆)alkyl or (C₁-C₆)alkyl group; Ra₂ represents a hydrogen or halogen atom, hydroxyl, -O(C₁-C₆)alkyl, -(C₁-C₆)alkyl group, a nitrogen-containing heterocycle containing from 3 to 7 ring members, or -O-(CH₂)_m-NR'R'' group; Ra₃ represents a hydrogen atom, -O(C₁-C₆)alkyl, -(C₁-C₆)alkyl group, a nitrogen-containing heterocycle containing from 3 to 7 ring members, or a CRy₁Ry₂NH(Ry₃) group; Ra₄ represents a hydrogen atom or a halogen atom, -O(C₁-C₆)alkyl group, -(C₁-C₆)alkyl group or a CRy₁Ry₂NH(Ry₃) group; it is assumed that Ra₁, Ra₂, Ra₃, Ra₄ and Ra₅ cannot simultaneously represent a hydrogen atom; Ra₃ and Ra₄ cannot simultaneously be a group -CRy₁Ry₂NH(Ry₃); Ra₁ and Ra₂ together with the carbon atoms carrying them, can form a heterocycle containing from 4 to 7 ring members selected from tetrahydrofuran, 1,4-dioxane, tetrahydropyran, tetrahydro-2H-pyran-4-amine and 1-(tetrahydro-2H-pyran4-yl) methanamine; and Ra₂ and Ra₃ together with the carbon atoms carrying them, can form a hydrocarbon ring containing from 4 to 7 ring members selected from cyclopentane, cyclopentanamine, N-cyclopentylglycinamide and 1-methylcyclopentane; m is an integer whose value is set to 1, 2 or 3; R' and R'' may be the same or different, are -(C₁-C₆₎alkyl group or R' and R'' along with the nitrogen atom carrying them form a heterocycle containing from 3 to 7 ring members; Ry₁ represents a hydrogen atom, -(C₁-C₆)alkyl group, -CH₂-cyclohexyl group or a 3-methoxyphenyl group; Ry₂ represents a hydrogen atom or -(C₁-C₆)alkyl group; Ry₃ represents: a hydrogen atom, a group -C(=O)-CHRy₄-NHRy₅, where Ry₄ represents a hydrogen atom or (C₁-C₆)alkyl group and Ry₅ represents a hydrogen atom, or metal group, or -(C₁-C₆)alkyl group which may be substituted by a hydroxyl group, -O(C₁-C₃)alkyl group, a cyclohexyl group, or a methylsulfonyl group; or Ry₁ and Ry₂ together with the carbon atom carrying them, form a cyclopropane, cyclobutane or tetrahydropyran group; or Ry₂ and Ry₃ together with carbon and nitrogen atoms carrying them, form, respectively, a pyrrolidine or piperidine group, its optical isomers and their addition salts with a pharmaceutically acceptable acid. Invention also relates to a pharmaceutical composition based on a compound of formula (I). (I).

EFFECT: technical result: obtained compounds are useful for the prevention and/or treatment of pathologies, which are the result of the activation of the RhoA/ROCK pathway and the phosphorylation of myosin light chain.

15 cl, 16 tbl