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1. A method of treating diabetes, which method involves treating a patient in need thereof with a therapeutically effective amount of a compound of formula (I):in which:
Ra is hydrogen, halogen, C(1-3)alkyl, C(1-3)alkoxy, hydroxyC(1-3)alkyl, C(1-3)alkylthio, C(1-3)alkylsulphinyl, aminoC(1-3)alkyl, mono- or di-C(1-3)alkylaminoC(1-3)alkyl, C(1-3)alkylcarbonylaminoC(1-3)alkyl, C(1-3)alkoxyC(1-3)alkylcarbonylaminoC(1-3)alkyl, C(1-3)alkylsulphonylaminoC(1-3)alkyl, C(1-3)alkylcarboxy, or C(1-3)alkylcarboxyC(1-3)alkyl; Rb is hydrogen, halogen, C(1-3)alkyl, or hydroxyC(1-3)alkyl, with the proviso that Ra and Rb are not simultaneously each hydrogen; or Ra and Rb together are (CH2)n where n is 3 or 4, to form, with the pyrimidine ring carbon atoms to which they are attached a fused 5- or 6-membered carbocyclic ring; or Ra and Rb together with the pyrimidine ring carbon atoms to which they are attached form a fused benzo or heteroaryl ring unsubstituted or substituted by 1, 2, 3 or 4 substituents which may be the same or different selected from the group consisting of halogen, C(1-4)alkyl, cyano, C(1-4)alkoxy or C(1-4)alkylthio, and mono to perfluoro-C(1-4)alkyl); Rc is hydrogen or C(1-3)alkyl; R2 is an aryl or heteroaryl group, unsubstituted or substituted by 1, 2, 3 or 4 substituents which may be the same or different selected from the group consisting of C(1-18)alkyl, C(1-18)alkoxy)C(1-18)alkylthio, arylC(1-18)alkoxy, hydroxy, halogen, CN, COR6, carboxy, COOR6, NR6COR7, CONR8R9, SO2NR8R9, NR6SO2R7, NR8R9, mono to perfluoro-C(1-4)alkyl, mono to perfluoro-C(1-4)alkoxyaryl, and arylC(1-4)alkyl; R3 is hydrogen, C(1-6)alkyl which may be unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of hydroxy, halogen, OR6, COR6, carboxy, COOR6, CONR8R9, NR8R9, NR8COR9, mono- or di-(hydroxyC(1-6)alkyl)amino and N-hydroxyC(1-6)alkyl-N—C(1-6)alkylamino; or R3 is Het-C(0-4)alkyl in which Het is a 5- to 7-membered heterocyclyl ring comprising N and optionally O or S, bonded through a carbon ring atom and in which N is unsubstituted or substituted by COR6, COOR6, CONR8R9, or C(1-6)alkyl unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of hydroxy, halogen, OR6, COR6, carboxy, COOR6, CONR8R9 and NR8R9; R4 is an aryl or a heteroaryl ring unsubstituted or substituted by 1, 2, 3 or 4 substituents which may be the same or different selected from the group consisting of C(1-18)alkyl, C(1-18)alkoxy, C(1-18)alkylthio, arylC(1-18)alkoxy, hydroxy, halogen, CN, COR6, carboxy, COOR6, NR6COR7, CONR8R9, SO2NR8R9, NR6SO2R7, NR8R9, mono to perfluoro-C(1-4)alkyl and mono to perfluoro-C(1-4)alkoxy; R5 is an aryl or heteroaryl ring which is unsubstituted or substituted by 1, 2, 3 or 4 substituents which may be the same or different selected from the group consisting of C(1-18)alkyl, C(1-18)alkoxy, C(1-18)alkylthio, arylC(1-18)alkoxy, hydroxy, halogen, CN, COR6, carboxy, COOR6, CONR8R9, NR6COR7, SO2NR8R9, NR6SO2R7, NR8R9, mono to perfluoro-C(1-4)alkyl and mono to perfluoro-C(1-4)alkoxy; R6 and R7 are independently hydrogen or C(1-20)alkyl; R8 and R9 may be the same or different and are selected from the group consisting of hydrogen and C(1-12)alkyl; or R8 and R9 together with the nitrogen to which they are attached form a 5- to 7 membered ring optionally containing one or more further heteroatoms which are oxygen, nitrogen or sulphur, and is unsubstituted or substituted by one or two substituents selected from the group consisting of hydroxy, oxo, C(1-4)alkyl, C(1-4)alkylCO, aryl, and aralkyl; or R8 and R9 may be the same or different and are selected from the group consisting of CH2R10 and CHR11CO2H, or a salt thereof; R10 is COOH or a salt thereof, COOR12, CONR6R7, CN, CH2OH or CH2OR6; R11 is an amino acid side chain; R12 is C(1-4)alkyl or a pharmaceutically acceptable in vivo hydrolysable ester group; n is 1 to 4; X is O or S; Y is (CH2)p(O)q in which p is 1, 2 or 3 and q is 0 or p is 2 or 3 and q is 1; and Z is O or a bond;or a pharmaceutically acceptable salt thereof. |
