| 摘要 |
Disclosed are 5-phenyl-indole-3-carboxylic acid derivatives as represented by general formula (II), wherein X is CH; L is a bond; R1 is -C(O)ORA; RA is H; R2 is H or F; R3 is Cl, F, or CN; R4 and R5 are H; R6 and R7 are independently H, F, or methoxy; R9 and R10 are H; R8 is alkoxy; hydroxyalkoxy; hydroxyalkyl; cyclopropyl or cyclobutyl substituted with hydroxy or hydroxyalkyl; hydroxyphenyl; azetidinyl, morpholinyl, oxetanyl, piperazinyl, piperidinyl, pyrrolidinyl, tetrahydrofuran, tetrahydro-2H-pyran, or triazolyl, wherein each of the heterocycles is optionally substituted with 1 substituent that is alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, hydroxy, hydroxyalkyl, or oxo; heterocyclealkoxy, wherein the heterocycle is azetidinyl, morpholinyl, oxetanyl, piperazinyl, piperidinyl, pyrrolidinyl, tetrahydrofuran, tetrahydro-2H-pyran, or triazolyl, wherein each is optionally substituted with 1 substituent that is alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, hydroxy, hydroxyalkyl, or oxo. Representative compounds include 6-chloro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carboxylic acid, 6-fluoro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carboxylic acid, 4,6-difluoro-5-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-1H-indole-3-carboxylic acid, 4,6-difluoro-5-(4-(1-(hydroxymethyl)cyclobutyl)phenyl)-1H-indole-3-carboxylic acid, 6-chloro-5-[3-fluoro-4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-1H-indole-3-carboxylic acid, 4,6-difluoro-5-{ 4-[1-(hydroxymethyl)cyclobutyl]phenyl)-1H-indole-3-carboxylic acid, 4,6-difluoro-5-[4-(tetrahydro-2H-pyran-2-yl)phenyl]-1H-indole-3-carboxylic acid, 6-fluoro-5-[4-(tetrahydro-2H-pyran-2-yl)phenyl]-1H-indole-3-carboxylic acid, 6-chloro-5-{ 4-[tetrahydro-2H-pyran-2-yl]phenyl} -1H-indole-3-carboxylic acid and 6-chloro-5-[4-(oxetan-2-ylmethoxy)phenyl]-1H-indole-3-carboxylic acid. Also disclosed is a pharmaceutical composition comprising a compound as defined above and at least one pharmaceutically acceptable excipient, diluent, or carrier, for treating or preventing chronic kidney disease, diabetic nephropathy, acute kidney injury, polycystic kidney disease, Type II diabetes, dyslipidemia or obesity in a mammal. |
