Patent CA-2088742-C (CA)
Title: Benzimidazole and imidazopyridine derivatives and their application
Inventor: WHITTAKER MARK
IPC: C07D471/04
Filed: 1991-08-15
Granted: 2002-02-12
Abstract: Compounds of general formula I;    wherein:      A1 is =N-, =CH- or =CR1-;      A2 is =N-, =CH- or =CR2-; provided that, when one of A1 and A2 is a nitrogen atom, the other of A1 and A2 is other than a nitrogen atom;      R represents hydrogen, -C1-C6 alkyl, -C2-C6 alkenyl, -C2-C6 alkynyl, halogen or -OC1-C6 alkyl;      R1 and R2 each independently represents hydrogen, -C1-C6 alkyl, -C2-C6 alkenyl, -C2-C6 alkynyl, halogen, -CN, -CO2H, -CO2C1-C6 alkyl, -CONH2, -CHO, -CH2OH, -CF3, -OC1-C6 alkyl, -SC1-C6 alkyl, -SOC1-C6 alkyl, -SO2C1-C6 alkyl, -NH2, -NHCOMe or -NO2, or R1 and R2 together with the carbon atoms to which they are attached form a fused phenyl ring;      R3 represents hydrogen, -C1-C6 alkyl, -C2-C6 alkenyl, -C2-C6 alkynyl, -OC1-C6 alkyl, -SC1-C6 alkyl, -(C1-C6 alkyl)OC1-C6 alkyl, -(C1-C6 alkyl)SC1-C6 alkyl, -CF3, -(C1-C6 alkyl)phenyl, -C3-C8 cycloalkyl, -C4-C8 cycloalkenyl, -(C1-C6 alkyl)C3-C8 cycloalkyl, -(C1-C6 alkyl)C4-C8 cycloalkenyl or thiophenyl;      R4 represents hydrogen, -C1-C6 alkyl, -C2-C6 alkenyl, -C2-C6 alkynyl, -CO2C1-C6 alkyl, -SC1-C6 alkyl, -(C1-C6 alkyl)SC1-C6 alkyl, -(C1-C6 alkyl)OC1-C6 alkyl, -(C1-C6 alkyl)phenyl or thiophenyl;      R5 represents hydrogen, -C1-C6 alkyl, -C2-C6 alkenyl, -C2-C6 alkynyl, -COC1-C6 alkyl, -CO2C1-C6 alkyl, -(CO2C1-C6 alkyl)phenyl, -(C1-C6 alkyl)CO2C1-C6 alkyl, -(C1-C6 alkyl)phenyl, -C3-C8 cycloalkyl, -C4-C8 cycloalkenyl or phenyl optionally substituted by one or more substituents selected from -C1-C6 alkyl, -OC1-C6 alkyl, halogen, -CF3, -CN; m is an integer from 0 to 3:      Z is either a -CR6R7R8 or -CR6=CR7R8 group; wherein each of R6, R7 and R8 independently represents hydrogen, halogen, -C1-C18 alkyl optionally substituted by one or more halogen atoms, -C2-C18 alkenyl, -C2-C18 alkynyl, -(C1-C6 alkyl) OC1-C18 alkyl, -(C1-C6 alkyl) SC1-C18 alkyl, -(C1-C6 alkyl)O(C1-C6 alkyl)OC1-C6 alkyl, -(C1-C6 alkyl)S(C1-C6 alkyl)OC1-C6 alkyl, -(C1-C6 alkyl)O(C1-C6 alkyl)SC1-C6 alkyl, - (C1-C6 alkyl)S(C1-C6 alkyl)SC1-C6 alkyl, -(C1-C6 alkyl)OC2-C6 alkenyl, -C3-C8 cycloalkyl, -C4-C8 cycloalkenyl, -(C1-C6 alkyl)C3-C8 cycloalkyl, -(C1-C6 alkyl)C4-C8 cycloalkenyl, -(C1-C6 alkyl)OC3-C8 cycloalkyl, -(C1-C6 alkyl)OC4-C8 cycloalkenyl, -(C1-C6 alkyl)SC3-C8 cycloalkyl, -(C1-C6 alkyl)SC4-C8 cycloalkenyl, -(C1-C6 alkyl)N(C1-C6 alkyl)2, -(C1-C6 alkyl)morpholino, -(C1-C6 alkyl)OCH2Ph, -CH2OSi(C1-C6 alkyl)3, -CH2OSiPh2C1-C6 alkyl or a group -D wherein D represents a group;    wherein n is an integer from 0 to 3, and each of R9, R10 and R11 is independently hydrogen, -C1-C6 alkyl, -OC1-C6 alkyl, -SC1-C6 alkyl, -N(C1-C6 alkyl)2, -C2-C6 alkenyl, -C2-C6 alkynyl, -OCH2Ph, halogen, -CN, -CF3, -CO2H, -CO2C1-C6 alkyl, -CONH2, -CONHC1-C6 alkyl, -CONH(C1-C6 alkyl)2, -CHO, -CH2OH, -NH2, -NHCOC1-C6 alkyl, -SOC1-C6 alkyl, or -SO2C1-C6 alkyl; 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.