IMIDAZO (4,5-C) PYRIDINE DERIVATIVES AS PAF ANTAGONISTS

摘要

Compounds of formula (I) wherein R<5> represents hydrogen, -alkyl, -alkenyl, -alkynyl, -CO alkyl, -CO2 alkyl, -(CO alkyl)phenyl, -(CO2 alkyl)phenyl, -(alkyl)O alkyl, -(alkyl)S alkyl, -alkyl(CO2 alkyl), -cycloalkyl, -cycloalkenyl or a group -D wherein D represents a group alpha wherein n is an integer from 0 to 3, and each of R<8> and R<9> is independently hydrogen, -alkyl, -alkenyl, -alkynyl, -halogen, -CH, -CO2H, -CO2 alkyl, -CONH2, -CONH alkyl, -CON(alkyl)2, -CHO, -CH2OH, -CF3, -O alkyl, -S alkyl, -SO alkyl, -SO2 alkyl, -NH2 or -NHCOMe; B represents a) a -(CH2)m group wherein m is an integer from 0 to 1 and the group A represents a 5- or 6-membered heterocyclic ring, which heterocyclic ring may be optionally fused to a benzene ring or to a further 5-, 6- or 7-membered heterocyclic ring containing one or more nitrogen atoms, wherein at least one of the said heterocyclic rings may also contain an oxygen or sulphur atom, and wherein any of the rings may be optionally substituted with one or more substituents selected from hydrogen, halogen, -perfluoroalkyl, hydroxyl, carbonyl, thiocarbonyl, carboxyl, -CONH2, a group -D wherein D is as defined above, -R<10>, -OR<10>, -SR<10>, -SOR<10>, -SO2R<10>, -NHR<10>, -NR<10>R<10>, -CO2R<10> or -CONHR<10> wherein R<10> is -alkyl, -alkenyl, -alkynyl, -cycloalkyl or -cycloalkenyl each of which is optionally substituted with one or more substituents selected from halogen, hydroxyl, amino, carboxyl, -perfluoroalkyl, -alkyl, -alkenyl, -alkynyl, -cycloalkyl, -cycloalkenyl, -O alkyl, -S alkyl, tetrazol-5-yl, a group -D wherein D is as defined above or a heteroaryl or heteroarylmethyl group; b) a -ZR<11> group wherein Z is -C(=O)-, -C(=O)O-, -C(=O)S-, -(alkyl)O-, -(alkyl)OC(=O)-, -C(=S)-, -C(=S)O-, -(alkyl)S-, -(alkyl)OC(=O)C(=O)O-, -(alkyl)OSO2-, -NHC(=O)O-, -(alkyl)OC(=O)NH-, -(alkyl)C(=O)O- group, or -(alkyl)OSi(alkyl)2-, -(alkyl)OSiPh2- group, and R<11> is hydrogen, -alkyl, -alkenyl, -alkynyl, -(alkyl)O-alkyl, -(alkyl)S alkyl, -(alkyl)O(alkyl)O alkyl, -cycloalkyl, -cycloalkenyl, a group D as defined above or a group A as defined above; c) a -CH2NR<12>R<13> group or a -CONR<12>R<13> group wherein each of R<12> and R<13> is independently hydrogen, -alkyl, -cycloalkyl, pyridyl, a group D as defined above or R<12> and R<13> together with the nitrogen atom to which they are attached form a 5 to 8 membered nitrogen-containing heterocyclic ring; and their pharmaceutically and veterinarily acceptable acid addition salts and hydrates are antagonists of platelet activating factor (PAF) and as such are useful in the treatment or amelioration of various diseases or disorders mediated by PAF.