Benzo[5,6]cycloheptapyridine compounds, compositions and method of treating allergies

A compound having the structural formula IB ##STR229## or a pharmaceutically acceptable salt or solvate thereof, wherein:

• one of a, b, c and d represents N or NR.sup.9 where R.sup.9 is O.sup.-, --CH.sub.3 or --(CH.sub.2).sub.n CO.sub.2 H where n is 1 to 3, and the remaining a, b, c and d groups are CH, which remaining a, b, c and d groups optionally substituted with R.sup.1 or R.sup.2 ;
• R.sup.1 and R.sup.2 are the same or different and each independently represents halo, --CF.sub.3, --OR.sup.10, --COR.sup.10, --SR.sup.10, --N(R.sup.10).sub.2, --NO.sub.2, --OC(O)R.sup.10, --CO.sub.2 R.sup.10, --OCO.sub.2 R.sup.11, alkynyl, alkenyl or alkyl, which alkyl or alkenyl groups are substituted with halo, --OR.sup.10 or --CO.sub.2 R.sup.10, said alkenyl group not containing --OH on a carbon containing double bond;
• R.sup.3 and R.sup.4 are the same or different and each independently represent H, any of the substituents of R.sup.1 and R.sup.2, or R.sup.3 and R.sup.4 together may represent a saturated or unsaturated C.sub.5 -C.sub.7 ring fused to the benzene ring;
• R.sup.5, R.sup.6, R.sup.7 and R.sup.8 each independently represent H, --CF.sub.3, --COR.sup.10, --CO.sub.2 R.sup.10, alkyl or aryl, which alkyl and aryl are optionally substituted with --OR.sup.10, --SR.sup.10, --N(R.sup.10).sub.2, --NO.sub.2, --COR.sup.10, --OCOR.sup.10, --OCO.sub.2 R.sup.11, --CO.sub.2 R.sup.10, --OPO.sub.3 R.sup.10, or one of R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are taken in combination with R as defined below to represent --(CH.sub.2).sub.r -- where r is 1 to 4 which is optionally substituted with lower alkyl, lower alkoxy, --CF.sub.3 or aryl, or R.sup.5 is combined with R.sup.6 to represent .dbd.O or .dbd.S, or R.sup.7 is combined with R.sup.8 to represent .dbd.O or .dbd.S;
• each R.sup.10 independently represents H, alkyl or aryl;
• R.sup.11 represents alkyl or aryl;
• the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent H, --R.sup.10, --OR.sup.11 or --OC(O)R.sup.10, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H.sub.2, --(OR.sup.11).sub.2, alkyl and H, (alkyl).sub.2, --H and --OC(O)R.sup.10, H and --OR.sup.10, H and halo, dihalo, .dbd.O, aryl and H, .dbd.NOR.sup.10 or --O--(CH.sub.2).sub.p --O-- where p is 2, 3 or 4 and R.sup.10 is as previously defined;
• Z represents O, S or .dbd.NR.sup.13 or wherein R.sup.13 represents --CN or R.sup.10 as previously defined;
• and
• R may be taken in combination with R.sup.5, R.sup.6, R.sup.7 or R.sup.8 as defined above, or R represents H, aryl, alkyl, --SR.sup.11, --N(R.sup.10).sub.2, cycloalkyl, alkenyl, alkynyl or --D wherein --D represents heterocycloalkyl selected from the group consisting of 2- or 3-tetrahydrofuranyl, 2- or 3-tetrahydrothienyl, 2-, 3- or 4-piperidinyl, 2- or 3-pyrrolidinyl, 2- or 3-piperazinyl, or 2- or 4-dioxanyl;
• ##STR230## wherein R.sup.3 and R.sup.4 are as previously defined and W is O, S or NR.sup.10 wherein R.sup.10 is as defined above, said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R.sup.10).sub.2, aryl, --CO.sub.2 R.sup.10, --OR.sup.12, --SR.sup.12, --N(R.sup.10).sub.2, --N(R.sup.10)CO.sub.2 R.sup.10, --COR.sup.12, --NO.sub.2 or --D, wherein --D and R.sup.10 are as defined above and R.sup.12 represents R.sup.10, --(CH.sub.2).sub.m OR.sup.10 or --(CH.sub.2).sub.q CO.sub.2 R.sup.10 is as previously defined, m is 1 to 4 and q is 0 to 4, said alkenyl and alkenyl and alkynyl R groups not containing --OH, --SH or --N(R.sup.10).sub.2 on a carbon containing a double or triple bond respectively and wherein alkyl (each occurrence) has up to 6 carbon atoms, wherein alkenyl and alkynyl (each occurrence) have up to 12 carbon atoms and wherein aryl (each occurrence) has 6 to 15 carbon atoms.

A compound having the structural formula IC ##STR231## or a pharmaceutically acceptable salt or solvate thereof, wherein:

• a represents NR.sup.9 and the remaining b, c and d groups represent CH, or one of b, c or d represents N or NR.sup.9 and the remaining a, b, c and d groups represent CH, where R.sup.9 is O.sup.- or --(CH.sub.2).sub.n CO.sub.2 H where n is 1 to 3, and wherein said remaining a, b, c and d groups optionally substituted with R.sup.1 or R.sup.2 ;
• R.sup.1 and R.sup.2 are the same or different and each independently represents halo, --CF.sub.3, --OR.sup.10, --COR.sup.10, --SR.sup.10, --N(R.sup.10).sub.2, --NO.sub.2, --OC(O)R.sup.10, --CO.sub.2 R.sup.10, --OCO.sub.2 R.sup.11, alkynyl, alkenyl or alkyl, which alkyl or alkenyl groups are substituted with halo, --OR.sup.10 or --CO.sub.2 R.sup.10, said alkenyl group not containing --OH on a carbon containing double bond;
• R.sup.3 and R.sup.4 are the same or different and each independently represent H, any of the substituents of R.sup.1 and R.sup.2, or R.sup.3 and R.sup.4 together may represent a saturated or unsaturated C.sub.5 -C.sub.7 ring fused to the benzene ring;
• R.sup.5, R.sup.6, R.sup.7 and R.sup.8 each independently represent H, --CF.sub.3, --COR.sup.10, --CO.sub.2 R.sup.10, alkyl or aryl, which alkyl and aryl are optionally substituted with --OR.sup.10, --SR.sup.10, --N(R.sup.10).sub.2, --NO.sub.2, --COR.sup.10, --OCOR.sup.10, --OCO.sub.2 R.sup.11, --CO.sub.2 R.sup.10, --OPO.sub.3 R.sup.10, or one of R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are taken in combination with R as defined below to represent --(CH.sub.2).sub.r -- where r is 1 to 4 which is optionally substituted with lower alkyl, lower alkoxy, --CF.sub.3 or aryl, or R.sup.5 is combined with R.sup.6 to represent .dbd.O or .dbd.S, or R.sup.7 is combined with R.sup.8 to represent .dbd.O or .dbd.S;
• each R.sup.10 independently represents H, alkyl or aryl;
• R.sup.11 represents alkyl or aryl;
• the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent H, --R.sup.10, --OR.sup.11 or --OC(O)R.sup.10, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H.sub.2, --(OR.sup.11).sub.2, alkyl and H, (alkyl).sub.2, --H and --OC(O)R.sup.10, H and --OR.sup.10, H and halo, dihalo, .dbd.O, aryl and H, .dbd.NOR.sup.10 or --O--(CH.sub.2).sub.p --O-- where p is 2, 3 or 4 and R.sup.10 is as previously defined;
• Z represents O, S or .dbd.NR.sup.13 or wherein R.sup.13 represents --CN or R.sup.10 as previously defined;
• and
• R may be taken in combination with R.sup.5, R.sup.6, R.sup.7 or R.sup.8 as defined above, or R represents H, aryl, alkyl, --SR.sup.11, --N(R.sup.10).sub.2, cycloalkyl, alkenyl, alkynyl or --D wherein --D represents heterocycloalkyl selected from the group consisting of 2- or 3-tetrahydrofuranyl, 2- or 3-tetrahydrothienyl, 2-, 3- or 4-piperidinyl, 2- or 3-pyrrolidinyl, 2- or 3-piperazinyl, or 2- or 4-dioxanyl;
• ##STR232## wherein R.sup.3 and R.sup.4 are as previously defined and W is O, S or NR.sup.10 wherein R.sup.10 is as defined above, said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R.sup.10).sub.2, aryl, --CO.sub.2 R.sup.10, --OR.sup.12, --SR.sup.12, --N(R.sup.10).sub.2, --N(R.sup.10)CO.sub.2 R.sup.10, --COR.sup.12, --NO.sub.2 or --D, wherein --D and R.sup.10 are as defined above and R.sup.12 represents R.sup.10, --(CH.sub.2).sub.m OR.sup.10 or --(CH.sub.2).sub.q CO.sub.2 R.sup.10 is as previously defined, m is 1 to 4 and q is 0 to 4, said alkenyl and alkenyl and alkynyl R groups not containing --OH, --SH or --N(R.sup.10).sub.2 on a carbon containing a double or triple bond respectively and wherein alkyl (each occurrence) has up to 6 carbon atoms, wherein alkenyl and alkynyl (each occurrence) have up to 12 carbon atoms and wherein aryl (each occurrence) has 6 to 15 carbon atoms.

A compound having the structural formula ID ##STR237## or a pharmaceutically acceptable salt or solvate thereof, wherein:

• a represents N and the remaining b, c and d groups are CH, which remaining b;
• c and d groups optionally are substituted with R.sup.1 or R.sup.2 ;
• R.sup.1 and R.sup.2 are the same or different and each independently represents halo, --CF.sub.3, --OR.sup.10, --COR.sup.10, --SR.sup.10, --N(R.sup.10).sub.2, --NO.sub.2, --OC(O)R.sup.10, --CO.sub.2 R.sup.10, --OCO.sub.2 R.sup.11, alkynyl, alkenyl or alkyl, which alkyl or alkenyl groups are optionally substituted with halo, --OR.sup.10 or --CO.sub.2 R.sup.10, said alkenyl group not containing --OH on a carbon containing double bond;
• R.sup.3 and R.sup.4 are the same or different and each independently represents H, any of the substituents of R.sup.1 and R.sup.2, or R.sup.3 and R.sup.4 together may represent a saturated or unsaturated C.sub.5 -C.sub.7 ring fused to the benzene ring;
• R.sup.5, R.sup.6, R.sup.7 and R.sup.8 each independently represent H, --CF.sub.3, --COR.sup.10, --CO.sub.2 R.sup.10, alkyl or aryl, which alkyl and aryl are optionally substituted with --OR.sup.10, --SR.sup.10, --N(R.sup.10).sub.2, --NO.sub.2, --COR.sup.10, --OCOR.sup.10, --OCO.sub.2 R.sup.11, --CO.sub.2 R.sup.10, --OPO.sub.3 R.sup.10, or one of R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are taken in combination with R as defined below to represent --(CH.sub.2).sub.r -- where r is 1 to 4 which is optionally substituted with lower alkyl, lower alkoxy, --CF.sub.3 or aryl, or R.sup.5 is combined with R.sup.6 to represent .dbd.O or .dbd.S, or R.sup.7 is combined with R.sup.8 to represent .dbd.O or .dbd.S;
• each R.sup.10 independently represents H, alkyl or aryl;
• R.sup.11 represents alkyl or aryl;
• the dotted line between carbon atoms 5 and 6 represents an optional double bond, such that when a double bond is present, A and B independently represent H, --R.sup.10, --OR.sup.11 or --OC(O)R.sup.10, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent --(OR.sup.11).sub.2, alkyl and H, (alkyl).sub.2, --H and --OC(O)R.sup.10, H and --OR.sup.10, H and halo, dihalo, .dbd.O, aryl and H, .dbd.NOR.sup.10 or --O--(CH.sub.2).sub.p --O-- where p is 2, 3 or 4 and R.sup.10 is as previously defined;
• Z represents O, S or .dbd.NR.sup.13 or wherein R.sup.13 represents --CN or R.sup.10 as previously defined;
• and
• R may be taken in combination with R.sup.5, R.sup.6, R.sup.7 or R.sup.8 as defined above, or R represents H, aryl, alkyl, --SR.sup.11, --N(R.sup.10).sub.2, cycloalkyl, alkenyl, alkynyl or --D wherein --D represents heterocycloalkyl selected from the group consisting of 2- or 3-tetrahydrofuranyl, 2- or 3-tetrahydrothienyl, 2-, 3- or 4-piperidinyl, 2- or 3-pyrrolidinyl, 2- or 3-piperazinyl, or 2- or 4-dioxanyl;
• ##STR238## wherein R.sup.3 and R.sup.4 are as previously defined and W is O, S or NR.sup.10 wherein R.sup.10 is as defined above, said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R.sup.10).sub.2, aryl, --CO.sub.2 R.sup.10, --OR.sup.12, --SR.sup.12, --N(R.sup.10).sub.2, --N(R.sup.10)CO.sub.2 R.sup.10, --COR.sup.12, --NO.sub.2 or --D, wherein --D and R.sup.10 are as defined above and R.sup.12 represents R.sup.10, --(CH.sub.2).sub.m OR.sup.10 or --(CH.sub.2).sub.q CO.sub.2 R.sup.10 is as previously defined, m is 1 to 4 and q is 0 to 4, said alkenyl and alkenyl and alkynyl R groups not containing --OH, --SH or --N(R.sup.10).sub.2 on a carbon containing a double or triple bond respectively and wherein alkyl (each occurrence) has up to 6 carbon atoms, wherein alkenyl and alkynyl (each occurrence) have up to 12 carbon atoms and wherein aryl (each occurrence) has 6 to 15 carbon atoms.