New bile acid conjugates with benzylamino substituted aromatic and heteroaromatic compounds useful for prevention and treatment of gall stones

摘要

Conjugates of bile acids with benzylamino-substituted monocyclic and bicyclic aromatic and heteroaromatic compounds are new. The conjugates are compounds of formula (I) and their salts, solvates and physiologically functional derivatives (including esters and prodrugs): P'-L-G (I) G = group of formula (a): K' = OR7, NR7R8, NH-(CH2)2-CO2H, NH-(CH2)2-SO3H, NH-CH2-CO2H, N(CH3)-CH2-CO2H, NH-CH(R9)-CO2H; or OKa; Ka = cation; R7 and R8 = H, alkyl, Ph, or Ph-CH2; Ph = phenyl optionally substituted with 5 groups; R9 = alkyl, benzyl, CH2OH, (CH2)2-SCH3, CH2CO2H, or (CH2)2-CO2H; R1-R6 = H, OR10, SR10, NR10R13, OCOR10; SCOR10, NHCOR10, SO2OR10, R10, or a bond to L (one of R1-R6 is a bond to L); R10 and R13 = H, alkyl, Ph, or Ph-CH2; L = alkyl with CH2 group(s) optionally replaced by -CH=CH-, -CC-, -NR11-, -CO-, -O-, -SO2- and/or -S-; R11 = H, alkyl, COR12, phenyl, or benzyl; R12 = H, alkyl, Ph, or Ph-CH2; P' = group of formula (B1) or (B2); A, B', D' and E = N or CH; R16-R24 = H, F, Cl, Br, I, alkyl, fluoro-alkyl, CN, NO2, NR25R26, OR25, OCOR25, COR25, COOR25, CONR25R26, SO2R25, SO2OR25, or SO2NR25R26, or a bond to L (one of R16-R24 is a bond to L); and R25 and R26 = H, alkyl, fluoro-alkyl, phenyl, or benzyl. Independent claims are also included for: (A) the preparation of compounds (I); and (B) medicaments containing compounds (I) and optionally a lipid-lowering agent.