BILE ACID DERIVATIVES AS FXR/TGR5 AGONISTS AND METHODS FOR USE THEREOF Russian patent published in 2019 - IPC C07J41/00 C07J43/00 A61K31/57 A61K31/575 A61P3/04 A61P3/10 A61P9/10 

FIELD: medicine; pharmaceuticals.

SUBSTANCE: invention relates to a compound represented by formula I, or a pharmaceutically acceptable salt thereof. In the IR_a formula is hydrogen or -C₁-C₈ alkyl; R_b is selected from a group consisting of: 1) -C(O)NR'₁₀R'₁₁; 2) -C(O)NHSO₂R₁; and 3) -SO₂R₁; R₁ is selected from a group consisting of: 1) -C₁-C₈ alkyl, unsubstituted or substituted with halogen, phenyl, carboxyl or hydroxyl; 2) -C₃-C₈ cycloalkyl, unsubstituted or substituted C₁-C₆ alkyl or halogen; bicyclo[2.2.1]heptane or 2-oxo-7,7-dimethylbicyclo[2.2.1]heptane; 3) phenyl unsubstituted or substituted with halogen, C₁-C₆ alkyl, halogen-C₁-C₆ alkyl, hydroxy-C₁-C₆ alkyl, C₁-C₆ alkoxy, halogen-C₁-C₆ alkoxy, piperidinyl, di(C₁-C₆ alkyl)amine, C₃-C₈ cycloalkyl, C₃-C₈ cycloalkyl substituted with halogen-C₁-C₆ alkyl, phenyl, carboxy, C₁-C₆ alkyloxycarbonyl, methoxycarbonyl-C₁-C₆ alkyl, 2-methylthiazol-4-yl, 4-methylthiazol-2-yl, isoxazol-5-yl, 2-methyloxazol-5-yl or 1,3,4-oxadiazol-2-yl; 1,3-benzodioxole; 1,4-benzodioxane; indane; naphthyl or 1,2,3,4-tetrahydronaphthalene; 4) 6-member heterocycloalkyl, in which two ring heteroatoms are selected from N, O and S, substituted with one or two groups selected from C₁-C₆ alkyl, oxo, C₁-C₆ alkylcarbonyl or 3-azabicyclo [3.1.0] hexane; 2-oxo-7-azaspiro[3.5]nonane or 6-azaspiro[2.5]octane; 5) five- or six-membered heteroaryl, in which one or two ring heteroatoms are selected from S and N, unsubstituted or substituted with C₁-C₆ alkyl, phenyl; 2,3-dihydroindole, substituted with acetyl, or quinoline, and 6) -NR₁₀R₁₁; R₂ is hydrogen; m is selected from 0, 1, 2 and 3; R₃ is hydrogen or hydroxyl; R₄ is hydrogen; R₅ and R₆ are independently selected from hydrogen or a protecting group for a hydroxy group selected from tert-butyldimethylsilyl, acetyl and N-methylcarbamoyl; R₇ is selected from -C₁-C₈ alkyl; R₁₀ and R₁₁ each is independently selected from hydrogen and -C₁-C₈ alkyl, or R₁₀ and R₁₁, taken together with the nitrogen atom to which they are bonded, form a five-seven-member heterocyclic ring optionally substituted with one to four groups selected from C₁-C₆ alkyl and halogen; R'₁₀ is C₁-C₈ alkyl; and R'₁₁ is hydrogen. Invention also relates to individual compounds, to a method of treating a disease or condition, to a pharmaceutical composition.

EFFECT: technical result is obtaining novel compounds having the properties of modulators of farnesoid X receptor (FXR).

25 cl, 12 tbl, 121 ex