Patent ID: 6410539
Filing Date: 2002-06-25
Classification: A61P,C07D

Abstract:
A compound of Formula (1): R5 is hydrogen, C1-4alkyl, phenylC1-4alkyl; R6 is hydrogen, C1-4alkyl, hydroxyC1-4alkyl, haloC1-4alkyl, dihaloC1-4alkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl, sulfanylC1-4alkyl, aminoC1-4alkyl, Nâ€”(C1-4alkyl)aminoC1-4alkyl, N,N-di-(C1-4alkyl)aminoC1-4alkyl or phenylC1-4alkyl; m is 0, 1 or 2; R1 is hydrogen, C1-4alkyl or C1-4alkanoyl; R12 and R13 are independently hydrogen or C1-4alkyl; Ar2 is phenyl or heteroaryl; p is 0 or 1; Ar3 is of the formula: wherein W, X, Y and Z are independently is CH or N, provided that at least two of W, X, Y and Z are CH and R2 and â€”(CH2)nR3 are attached to ring carbon atoms;R2 is a group of the Formula (2): wherein R7 is hydrogen or C1-4alkyl, R8 is â€”(CH2)qâ€”R10 wherein q is 0-4 and R10 is C1-4alkylsulfanyl, C1-4alkylsulfinyl, C1-4alkylsulfonyl, hydroxy, C1-4alkoxy, carbamoyl, Nâ€”C1-4alkylcarbamoyl, N,N-(diC1-4alkyl)carbamoyl, C1-4alkyl, phenyl, thienyl, or C1-4alkanoylamino; R9 is hydroxy, C1-6alkoxy, C3-9cycloalkyloxy, heterocyclyloxy, heterocyclylC1-4alkoxy or â€”NHâ€”SO2â€”R11 wherein R11 represents, trifluoromethyl, C1-4alkyl, phenyl, heteroaryl, arylC1-4alkyl or heteroarylC1-4alkyl;or R2 represents a lactone of Formula (3) the group of Formula (2) or (3) having L or D configuration at the chiral alpha carbon in the corresponding free amino acid;n is 0, 1 or 2; R3 is phenyl or heteroaryl; phenyl and heteroaryl rings in R3, R5, R6, R9, R11 and Ar2 are independently optionally substituted on ring carbon atoms by up to three substituents selected from C1-4alkyl, halogen, hydroxy, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkanoyl, C1-4alkanoyloxy, amino, C1-4alkylamino, di(C1-4alkyl)amino, C1-4alkanoylamino, nitro, cyano, carboxy, thiol, C1-4alkylsulfanyl, C1-4alkylsulfinyl, C1-4alkylsulfonyl, C1-4alkanesulphonamido, N-(C1-4alkylsulphonyl)-Nâ€”C1-4alkylamino, aminosulfonyl, N-(C1-4alkyl)aminosulfonyl, N,N-di(C1-4alkyl)aminosulfonyl, carbamoyl, Nâ€”(C1-4alkyl)carbamoyl, N,N-(diC1-4alkyl)carbamoyl, carbamoylC1-4alkyl, Nâ€”(C1-4alkyl)carbamnoylC1-4alkyl, N,N-(diC1-4alkyl)carbamoylC1-4alkyl, hydroxyC1-4alkyl and C1-4alkoxyC1-4alkyl and on ring NH groups by C1-4alkyl, C1-4alkanoyl, C1-4alkylsulfonyl, haloC1-4alkyl, difluoromethyl or trifluoromethyl; wherein, in each of Ar2, R2 and R3, each said heterocyclyl group is a 5- or 6-membered monocyclic ring containing 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur; and each said heteroaryl group is a 5-10 membered monocyclic heteroaryl ring containing up to 3 heteroatoms selected from nitrogen, oxygen and sulphur; provided that:when n is 0, Ar3 is substituted by R2 in the 4-position and â€”(CH2)nR3 in the 3- or 5-position; and when n is 1 or 2, Ar3 is substituted by R2 in the 3- or 5-position and â€”(CH2)nR3 in the 4-position; or a pharmaceutically acceptable salt, prodrug or solvate thereof.