IMPROVED APELIN RECEPTOR AGONISTS (APJ) AND THEIR USE Russian patent published in 2022 - IPC C07D231/14 C07D401/12 C07D401/14 C07D403/04 C07D403/12 C07D403/14 C07D405/12 C07D407/12 C07D409/04 C07D413/12 C07D417/04 C07D417/12 C07D417/14 C07D491/107 A61K31/415 A61K31/4196 A61K31/422 A61K31/4245 A61K31/427 A61K31/439 A61K31/4439 A61K31/454 A61K31/497 A61K31/5377 A61K31/55 A61P3/00 A61P11/06 

FIELD: pharmaceutics.

SUBSTANCE: present invention relates to a compound represented by the formula I:

or its pharmaceutically acceptable salt, where R₁ is represented by the formula:

,

where is a monocyclic C₆ aryl or 5-7-element heteroaryl group containing 1-2 heteroatoms selected from N, O or S; each A is independently optionally fluorinated C_1-8 alkyl, optionally fluorinated C_1-8 alkoxy, optionally fluorinated C_3-8 cycloalkyl, -CF₃ or halogen; n is 1 or 2; where the first substituent A is located ortho to an attachment point from depicted pyrazole ring; R₂ is C_3-8 alkyl, C_1-8 alkyl-C_3-8 cycloalkyl, C_3-8 cycloalkyl or C_6-10 aryl, substituted C_1-8 alkyl; R₄ is optionally fluorinated C_1-8 alkyl, C_1-8 alkyl-C₆ aryl, C_1-8 alkyl-C_3-8 cycloalkyl, C_1-8 alkyl-5-14-element heteroaryl, where heteroaryl contains from 1 to 4 heteroatoms selected from N, O or S, or (CH₂)_xNR₇R₈; R₅ is optionally substituted C_1-8 alkyl, C_1-8 alkylamino, C_1-8 alkylamido, C_2-8 alkyl-C₆ aryl, C_1-8 alkyl-C_3-8 cycloalkyl, C_1-8 alkyl-5-14-element heteroaryl, where heteroaryl contains from 1 to 4 heteroatoms selected from N, O or S, C_1-8 alkyltetrazole-5-one, (CH₂)_xNR₇R₈, (CH₂)xOR₇, (CH₂)xCONR₇R₈, (CH₂)_xCOR₇, (CH₂)_xxCO₂R₇; R₆ is H or each of R₇ and R₈ is independently H, C_1-8 alkyl-5-14-element heteroaryl, C_3-8 cycloalkyl, -(CH₂)_xCO₂R₉ or 5-17-element heteroaryl, where heteroaryl contains from 1 to 4 heteroatoms selected from N, O, S; or R₇ and R₈ together form 3-9-element ring that can contain one or two heteroatoms selected from N or O; or R₉ is H or C_1-8 alkyl; each x is independently equal to 0, 1, 2, 3, 4, 5, 6, 7 or 8; and each xx is independently equal to 0, 1, 2, 3, 4, 5, 6, 7 or 8. Pharmaceutical compositions and applications for the treatment of disorders related to an apelin receptor (APJ) are also proposed.

EFFECT: technical result consists in obtaining new organic compounds that are agonists of the apelin receptor (APJ) and that can be used to reduce blood pressure.

23 cl, 5 tbl