Benzopyrido piperidine, piperidylidene and piperazine compounds, compositions, methods of manufacture and methods of use

A compound represented by the structural formula ##STR97## or a pharmaceutically acceptable salt or solvate thereof, wherein:

• one of a, b, c and d represents nitrogen or --NR.sup.11, where R.sup.11 is --O.sup.-, --CH.sub.3, or --(CH.sub.2).sub.p CO.sub.2 H where p is 1 to 3, and the remaining a, b, c and d groups are CH which may be optionally substituted with R.sup.1 or R.sup.2 ;
• R.sup.1 and R.sup.2 may be the same or different and each independently represents halo, --CF.sub.3, --OR.sup.10, --C(O)R.sup.10, --S(O).sub.e R.sup.12 where e is 0, 1 or 2, --N(R.sup.10).sub.2, --NO.sub.2, SH, CN, --OC(O)R.sup.10, --CO.sub.2 R.sup.10, --OCO.sub.2 R.sup.12, --NR.sup.10 C(O)R.sup.10, C.sub.1 -C.sub.20 alkyl, C.sub.2 -C.sub.12 alkenyl or C.sub.2 -C.sub.12 alkynyl, which alkyl or alkenyl groups may be substituted with halo, --OR.sup.10 or --CO.sub.2 R.sup.10, or R.sup.1 and R.sup.2 may together form a benzene ring fused to the pyridine ring;
• R.sup.10 represents H, C.sub.1 -C.sub.20 alkyl or C.sub.6 -C.sub.15 aryl;
• R.sup.12 represents C.sub.1 -C.sub.20 alkyl or C.sub.6 -C.sub.15 aryl;
• R.sup.3 and R.sup.4 may be the same or different and each independently represents H or any of the substituents of R.sup.1 and R.sup.2, or
• R.sup.3 and R.sup.4 may be taken together to 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 represents H, --CF.sub.3, --CO.sub.2 R.sup.10, --C(O)R.sup.10, C.sub.1 -C.sub.20 alkyl or C.sub.6 -C.sub.15 aryl, which alkyl or aryl may be substituted with --OR.sup.10, --SR.sup.10, --N(R.sup.10).sub.2, --NO.sub.2, --C(O)R.sup.10, --OC(O)R.sup.12, --OCO.sub.2 R.sup.12, --CO.sub.2 R.sup.10 and --OPO.sub.3 (R.sup.10).sub.2, or one of R.sup.5, R.sup.6, R.sup.7 and R.sup.8 may be taken in combination with R as defined below to represent --(CH.sub.2).sub.r --where r is 1 to 4, said combination being optionally substituted with C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, --CF.sub.3 or C.sub.6 -C.sub.15 aryl, or R.sup.5 may be combined with R.sup.6 to represent .dbd.O or .dbd.S, and/or R.sup.7 may be combined with R.sup.8 to represent .dbd.O or .dbd.S;
• T represents carbon or nitrogen, with the dotted line attached to T representing an optional double bond when T is carbon;
• m and n are integers 0, 1, 2, or 3, such that the sum of m plus n equals 0 to 3;
• when m plus n equals 1, X represents --O--, --S(O).sub.e --wherein e is 0, 1 or 2, --NR.sup.10 --, --C(O)NR.sup.10 --, --NR.sup.10 C(O)--, --C(S)NR.sup.10 --, --NR.sup.10 C(S)--, --CO.sub.2 --or --O.sub.2 C--, where R.sup.10 is a defined above;
• when m plus n equals 2, X represents --O--, --S(O).sub.e --where e is 0, 1 or 2, or --NR.sup.10 ;
• when m plus n represents 0, X can be any substituent for m plus n equalling 1 and X can also be a direct bond, cyclopropylene or propenylene;
• when m plus n equals 3 then X equals a direct bond;
• each R.sup.a may be the same of different, and each independently represents H, C.sub.1 -C.sub.6 alkyl or phenyl;
• Z represents .dbd.O, .dbd.S or .dbd.NR.sup.13 with R.sup.13 equal to R.sup.10 or --CN, wherein R.sup.10 is as defined above, such that
• (a) when Z is O, 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, C.sub.1 -C.sub.20 alkyl, C.sub.6 -C.sub.15 aryl, --SR.sup.12, --N(R.sup.10).sub.2, C.sub.3 -C.sub.20 cycloalkyl, C.sub.2 -C.sub.12 alkenyl, C.sub.2 -C.sub.12 alkynyl or --D wherein --D represents C.sub.3 -c.sub.15 heterocycloalkyl, ##STR98## wherein R.sup.3 and R.sup.4 are as previously defined and W is O, S or NR.sup.10, and where Y is N or NR.sup.11,
• said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R.sup.10).sub.2, C.sub.6 -C.sub.15 aryl, --CO.sub.2 R.sup.10, --OR.sup.14, --SR.sup.14, --N(R.sup.10).sub.2, --N(R.sup.10)CO.sub.2 R.sup.10, --COR.sup.14, --NO.sub.2 or --D, wherein --D and R.sup.10 are as defined above and R.sup.14 represents R.sup.10, --(CH.sub.2).sub.r OR.sup.10 or --(CH.sub.2).sub.q CO.sub.2 R.sup.10 wherein r is 1 to 4, q is 0 to 4;
• said alkenyl and alkynyl R groups not containing --OH, --SH or --N(R.sup.10).sub.2 on a carbon in a double or triple bond respectively;
• and
• (b) when Z represents .dbd.S, R represents in addition to those R groups above, C.sub.6 -C.sub.15 aryloxy or C.sub.1 -C.sub.20 alkoxy;
• and
• (c) where Z represents .dbd.NR.sup.50, R represents H, C.sub.1 -C.sub.20 alkyl, C.sub.6 -C.sub.15 aryl, N(R.sup.10).sub.2, C.sub.3 -C.sub.20 cycloalkyl, C.sub.2 -C.sub.12 alkenyl or C.sub.2 -C.sub.12 alkynyl.