Carboxamide amino acid heterobicyclic PAF antagonists

A compound of formula I;

• ##STR24## wherein:
• A.sup.1 is .dbd.N--, .dbd.CH-- or .dbd.CR.sup.1 --;
• A.sup.2 is --N.dbd., --CH.dbd. or --CR.sup.2 .dbd.;
• each of R.sup.1 and R.sup.2 independently represents hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, halogen, CN, CO.sub.2 H, CO.sub.2 C.sub.1 -C.sub.6 alkyl, CONH.sub.2, CHO, CH.sub.2 OH, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, SOC.sub.1 -C.sub.6 alkyl, SO.sub.2 C.sub.1 -C.sub.6 alkyl, NH.sub.2, NHCOMe or NO.sub.2 or R.sup.1 and R.sup.2 together with the carbon atoms to which they are attached form a fused phenyl ring;
• R.sup.3 represents hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, Cl-C6 alkoxy, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkoxy (C.sub.1 -C.sub.6 alkyl), C.sub.1 -C.sub.6 alkylthio (C.sub.1 -C.sub.6 alkyl), CF.sub.3, phenyl (C.sub.1 -C.sub.6 alkyl), C.sub.3 -C.sub.8 cycloalkyl or thiophenyl;
• R.sup.4 represents hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, CO.sub.2 C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylthio (C.sub.1 -C.sub.6 alkyl), C.sub.1 -C.sub.6 alkoxy (C.sub.1 -C.sub.6 alkyl), phenyl (C.sub.1 -C.sub.6 alkyl) or thiophenyl;
• R.sup.5 represents hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sup.6 alkenyl, halogen or C.sub.1 -C.sub.6 alkoxy;
• X represents an oxygen or a sulphur atom;
• R.sup.6 represents hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, COC.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy (C.sub.1 -C.sub.6 alkyl), C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.8 cycloalkenyl or a group D wherein D represents a group:
• ##STR25## wherein n is an integer from 0 to 3, and each of R.sup.9 and R.sup.10 is independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, halogen, CN, CO.sub.2 H, CO.sub.2 C.sub.1 -C.sub.6 alkyl, CONH.sub.2, CHO, CH.sub.2 OH, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, SOC.sub.1 -C.sub.6 alkyl, SO.sub.2 C.sub.1 -C.sub.6 alkyl, NH.sub.2 or NHCOMe;
• or R.sup.6 together with R.sup.7 and the atoms to which they are attached forms a 5 to 8 membered nitrogen-containing heterocyclic ring;
• each of R.sup.7 and R.sup.8 independently represents hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, CO.sub.2 C.sub.1 -C.sub.6 alkyl (C.sub.1 -C.sub.6 alkyl), C.sub.1 -C.sub.6 alkylthio (C.sub.1 -C.sub.6 alkyl), C.sub.1 -C.sub.6 alkoxy (C.sub.1 -C.sub.6 alkyl), benzoxy (C.sub.1 -C.sub.6 alkyl), a side chain of a naturally occurring amino acid or a group D as defined above;
• or R.sup.7 together with R.sup.8 and the atoms to which they are attached forms a 5 to 8 membered nitrogen-containing heterocyclic ring;
• or R.sup.7 and R.sup.8 together with the carbon atom to which they are attached form a C.sub.3 -C.sub.8 cycloalkyl ring;
• B represents a) a ZR.sup.11 group wherein Z is --C(.dbd.O)--, --C(.dbd.O)O--, --CH.sub.2 O--, --CH.sub.2 OC(.dbd.O)--, --C(.dbd.S)--, --C(.dbd.S)O-- or --CH.sub.2 S-- and R.sup.11 is C.sub.1 -C.sub.18 alkyl, C.sub.2 -C.sub.18 alkenyl, C.sub.1 -C.sub.6 alkoxy (C.sub.1 -C.sub.6 alkyl), C.sub.1 -C.sub.6 alkylthio (C.sub.1 -C.sub.6 alkyl), C.sub.1 -C.sub.6 alkoxy (CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2), C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.8 cycloalkenyl, pyridyl or a group D as defined above;
• b) a CH.sub.2 NR.sup.12 R.sup.13 group or a CONR.sup.12 R.sup.13 group wherein each of R.sup.12 and R.sup.13 is independently hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, pyridyl, a group D as defined above or R.sup.12 and R.sup.13 together with the nitrogen atom to which they are attached form a 5 to 8 membered nitrogen-containing heterocyclic ring;
• c) a 5- or 6-membered aromatic heterocyclic ring containing one or more heteroatoms selected from nitrogen, oxygen and sulphur and the ring may be optionally substituted with one or more substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, halogen, CF.sub.3 and CN;