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

Claim 2

A compound having the structural formula IA ##STR227## or a pharmaceutically acceptable salt or solvate thereof, wherein: one of a, b, c and d represents N or NR 9 where R 9 is O - , --CH 3 or --(CH 2 ) n CO 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 are substituted with R 1 or R 2 ; R 1 and R 2 are the same or different and each independently represents halo, --CF 3 , --OR 10 , --COR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --OC(O)R 10 , --CO 2 R 10 , --OCO 2 R 11 , alkynyl, alkenyl or alkyl, which alkyl or alkenyl groups are optionally substituted with halo, --OR 10 or --CO 2 R 10 , said alkenyl group not containing --OH on a carbon containing double bond; R 3 and R 4 are the same or different and each independently represent H, any of the substituents of R 1 and R 2 , or R 3 and R 4 together may represent a saturated or unsaturated C 5 -C 7 ring fused to the benzene ring; R 5 , R 6 , R 7 and R 8 each independently represent H, --CF 3 , --COR 10 , --CO 2 R 10 , alkyl or aryl, which alkyl and aryl are optionally substituted with --OR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --COR 10 , --OCOR 10 , --OCO 2 R 11 , --CO 2 R 10 , --OPO 3 R 10 , or one of R 5 , R 6 , R 7 and R 8 are taken in combination with R as defined below to represent --(CH 2 ) r -- where r is 1 to 4 which is optionally substituted with lower alkyl, lower alkoxy, --CF 3 or aryl, or R 5 is combined with R 6 to represent ═O or ═S, or R 7 is combined with R 8 to represent ═O or ═S; each R 10 independently represents H, alkyl or aryl; R 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 10 , --OR 11 or --OC(O)R 10 , and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2 , --(OR 11 ) 2 , alkyl and H, (alkyl) 2 , --H and --OC(O)R 10 , H and --OR 10 , H and halo, dihalo, ═O, aryl and H, ═NOR 10 or --O--(CH 2 ) p --O-- where p is 2, 3 or 4 and R 10 is as previously defined; Z represents O, S or ═NR 13 or wherein R 13 represents --CN or R 10 as previously defined; and R may be taken in combination with R 5 , R 6 , R 7 or R 8 as defined above, or R represents H, aryl, alkyl, --SR 11 , --N(R 10 ) 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; ##STR228## wherein R 3 and R 4 are as previously defined and W is O, S or NR 10 wherein R 10 is as defined above, said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R 10 ) 2 , aryl, --CO 2 R 10 , --OR 12 , --SR 12 , --N(R 10 ) 2 , --N(R 10 )CO 2 R 10 , --COR 12 , --NO 2 or --D, wherein --D and R 10 are as defined above and R 12 represents R 10 , --(CH 2 ) m OR 10 or --(CH 2 ) q CO 2 R 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 10 ) 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.

Claim 3

A compound as defined in claim 1 wherein Z is O or S.

Claim 4

A compound as defined in claim 1 wherein R represents alkyl, cycloalkyl, alkenyl, aryl or alkyl substituted with OR 12 , SR 12 , N(R 10 ) 2 or COR 12 .

Claim 5

A compound according to claim 3 wherein Z is O.

Claim 6

A compound according to claim 4 wherein R 3 represents halo and R 4 represents hydrogen.

Claim 7

A compound according to claim 5 wherein R 5 , R 6 , R 7 and R 8 represent H.

Claim 8

A compound according to claim 6 wherein A and B represent H 2 .

Claim 9

A compound of formula IA as defined in claim 1 having the name: 8-chloro-11-(1-acetyl-4-piperazinyl)-6,11-dihydro-5Hbenzo[5,6]cyclohepta[1,2-b]pyridine; 5-methyl-8-chloro-(1-acetyl-4-piperazinyl)-6,11-dihydro-5Hbenzo[5,6]cyclohepta[1,2-b]pyridine; 8-chloro-11-[1-acetyl-2-methyl-4-piperazinyl]-6,11-dihydro-5Hbenzo[5,6]cyclohepta[1,2-b]pyridine; 8-chloro-11-[1-acetyl-2,6-dimethyl-4-piperazinyl]-6,11-dihydro-5Hbenzo[5,6]cyclohepta[1,2-b]pyridine; 8-chloro-11-(1-methoxyacetyl-4-piperazinyl)-6,11-dihydro-5Hbenzo[5,6]cyclohepta[1,2-b]pyridine; 8-chloro-11-(1-formyl-4-piperazinyl)-6,11-dihydro-5Hbenzo[5,6]cyclohepta[1,2-b]pyridine; 2-8-chloro-5,6-dihydro-11Hbenzo[5,6]cyclohepta[1,2-b]pyridine-11-yl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one.

Claim 10

The compound of claim 1 which is: 8-chloro-11-(1-acetyl-4-piperazinyl)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine.

Claim 11

A pharmaceutical composition comprising a compound of formula IA as defined in claim 1 in combination with a pharmaceutically acceptable carrier.

Claim 12

A method of treating allergy comprising administering a compound of formula IA as defined in claim 1 to a mammal in need of such treatment in an amount effective to treat allergy.

Claim 13

A method of treating inflammation comprising administering to a mammal in need of such treatment an antiinflammatory effective amount of a compound of formula IA as defined in claim 1.

Claim 14

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 9 where R 9 is O - , --CH 3 or --(CH 2 ) n CO 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 1 or R 2 ; R 1 and R 2 are the same or different and each independently represents halo, --CF 3 , --OR 10 , --COR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --OC(O)R 10 , --CO 2 R 10 , --OCO 2 R 11 , alkynyl, alkenyl or alkyl, which alkyl or alkenyl groups are substituted with halo, --OR 10 or --CO 2 R 10 , said alkenyl group not containing --OH on a carbon containing double bond; R 3 and R 4 are the same or different and each independently represent H, any of the substituents of R 1 and R 2 , or R 3 and R 4 together may represent a saturated or unsaturated C 5 -C 7 ring fused to the benzene ring; R 5 , R 6 , R 7 and R 8 each independently represent H, --CF 3 , --COR 10 , --CO 2 R 10 , alkyl or aryl, which alkyl and aryl are optionally substituted with --OR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --COR 10 , --OCOR 10 , --OCO 2 R 11 , --CO 2 R 10 , --OPO 3 R 10 , or one of R 5 , R 6 , R 7 and R 8 are taken in combination with R as defined below to represent --(CH 2 ) r -- where r is 1 to 4 which is optionally substituted with lower alkyl, lower alkoxy, --CF 3 or aryl, or R 5 is combined with R 6 to represent ═O or ═S, or R 7 is combined with R 8 to represent ═O or ═S; each R 10 independently represents H, alkyl or aryl; R 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 10 , --OR 11 or --OC(O)R 10 , and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2 , --(OR 11 ) 2 , alkyl and H, (alkyl) 2 , --H and --OC(O)R 10 , H and --OR 10 , H and halo, dihalo, ═O, aryl and H, ═NOR 10 or --O--(CH 2 ) p --O-- where p is 2, 3 or 4 and R 10 is as previously defined; Z represents O, S or ═NR 13 or wherein R 13 represents --CN or R 10 as previously defined; and R may be taken in combination with R 5 , R 6 , R 7 or R 8 as defined above, or R represents H, aryl, alkyl, --SR 11 , --N(R 10 ) 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 3 and R 4 are as previously defined and W is O, S or NR 10 wherein R 10 is as defined above, said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R 10 ) 2 , aryl, --CO 2 R 10 , --OR 12 , --SR 12 , --N(R 10 ) 2 , --N(R 10 )CO 2 R 10 , --COR 12 , --NO 2 or --D, wherein --D and R 10 are as defined above and R 12 represents R 10 , --(CH 2 ) m OR 10 or --(CH 2 ) q CO 2 R 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 10 ) 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.

Claim 15

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 9 where R 9 is O - , --CH 3 or --(CH 2 ) n CO 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 1 or R 2 ; R 1 and R 2 are the same or different and each independently represents halo, --CF 3 , --OR 10 , --COR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --OC(O)R 10 , --CO 2 R 10 , --OCO 2 R 11 , alkynyl, alkenyl or alkyl, which alkyl or alkenyl groups are substituted with halo, --OR 10 or --CO 2 R 10 , said alkenyl group not containing --OH on a carbon containing double bond; R 3 and R 4 are the same or different and each independently represent H, any of the substituents of R 1 and R 2 , or R 3 and R 4 together may represent a saturated or unsaturated C 5 -C 7 ring fused to the benzene ring; R 5 , R 6 , R 7 and R 8 each independently represent H, --CF 3 , --COR 10 , --CO 2 R 10 , alkyl or aryl, which alkyl and aryl are optionally substituted with --OR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --COR 10 , --OCOR 10 , --OCO 2 R 11 , --CO 2 R 10 , --OPO 3 R 10 , or one of R 5 , R 6 , R 7 and R 8 are taken in combination with R as defined below to represent --(CH 2 ) r -- where r is 1 to 4 which is optionally substituted with lower alkyl, lower alkoxy, --CF 3 or aryl, or R 5 is combined with R 6 to represent ═O or ═S, or R 7 is combined with R 8 to represent ═O or ═S; each R 10 independently represents H, alkyl or aryl; R 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 10 , --OR 11 or --OC(O)R 10 , and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2 , --(OR 11 ) 2 , alkyl and H, (alkyl) 2 , --H and --OC(O)R 10 , H and --OR 10 , H and halo, dihalo, ═O, aryl and H, ═NOR 10 or --O--(CH 2 ) p --O-- where p is 2, 3 or 4 and R 10 is as previously defined; Z represents O, S or ═NR 13 or wherein R 13 represents --CN or R 10 as previously defined; and R may be taken in combination with R 5 , R 6 , R 7 or R 8 as defined above, or R represents H, aryl, alkyl, --SR 11 , --N(R 10 ) 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 3 and R 4 are as previously defined and W is O, S or NR 10 wherein R 10 is as defined above, said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R 10 ) 2 , aryl, --CO 2 R 10 , --OR 12 , --SR 12 , --N(R 10 ) 2 , --N(R 10 )CO 2 R 10 , --COR 12 , --NO 2 or --D, wherein --D and R 10 are as defined above and R 12 represents R 10 , --(CH 2 ) m OR 10 or --(CH 2 ) q CO 2 R 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 10 ) 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.

Claim 16

A compound as defined in claim 13 wherein Z is O or S.

Claim 17

A compound as defined in claim 13 wherein R represents alkyl, cycloalkyl, alkenyl, aryl or alkyl substituted with OR 12 , SR 12 , N(R 10 ) 2 or COR 12 .

Claim 18

A compound according to claim 15 wherein Z is O.

Claim 19

A compound according to claim 16 wherein R 3 represents halo and R 4 represents hydrogen.

Claim 20

A compound according to claim 17 wherein R 5 , R 6 , R 7 and R 8 represent H.

Claim 21

A compound according to claim 18 wherein A and B represent H 2 .

Claim 22

A compound of formula IB as defined in claim 13 having the name: 8-chloro-11-[1-acetyl-4-piperidinyl]-11H-benzo[5,6]cyclohepta[1,2-b]pyridine; or 8-chloro-11-(1-acetyl-4-piperidyl)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-c]pyridine.

Claim 23

A pharmaceutical composition comprising a compound of formula IB as defined in claim 13 in combination with a pharmaceutically acceptable carrier.

Claim 24

A method of treating allergy comprising administering a compound of formula IB as defined in claim 13 to a mammal in need of such treatment in an amount effective to treat allergy.

Claim 25

A method of treating inflammation comprising administering to a mammal in need of such treatment an antiinflammatory effect amount of a compound of formula IB as defined in claim 13.

Claim 26

A compound having the structural formula IC ##STR231## or a pharmaceutically acceptable salt or solvate thereof, wherein: a represents NR 9 and the remaining b, c and d groups represent CH, or one of b, c or d represents N or NR 9 and the remaining a, b, c and d groups represent CH, where R 9 is O - or --(CH 2 ) n CO 2 H where n is 1 to 3, and wherein said remaining a, b, c and d groups optionally substituted with R 1 or R 2 ; R 1 and R 2 are the same or different and each independently represents halo, --CF 3 , --OR 10 , --COR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --OC(O)R 10 , --CO 2 R 10 , --OCO 2 R 11 , alkynyl, alkenyl or alkyl, which alkyl or alkenyl groups are substituted with halo, --OR 10 or --CO 2 R 10 , said alkenyl group not containing --OH on a carbon containing double bond; R 3 and R 4 are the same or different and each independently represent H, any of the substituents of R 1 and R 2 , or R 3 and R 4 together may represent a saturated or unsaturated C 5 -C 7 ring fused to the benzene ring; R 5 , R 6 , R 7 and R 8 each independently represent H, --CF 3 , --COR 10 , --CO 2 R 10 , alkyl or aryl, which alkyl and aryl are optionally substituted with --OR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --COR 10 , --OCOR 10 , --OCO 2 R 11 , --CO 2 R 10 , --OPO 3 R 10 , or one of R 5 , R 6 , R 7 and R 8 are taken in combination with R as defined below to represent --(CH 2 ) r -- where r is 1 to 4 which is optionally substituted with lower alkyl, lower alkoxy, --CF 3 or aryl, or R 5 is combined with R 6 to represent ═O or ═S, or R 7 is combined with R 8 to represent ═O or ═S; each R 10 independently represents H, alkyl or aryl; R 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 10 , --OR 11 or --OC(O)R 10 , and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2 , --(OR 11 ) 2 , alkyl and H, (alkyl) 2 , --H and --OC(O)R 10 , H and --OR 10 , H and halo, dihalo, ═O, aryl and H, ═NOR 10 or --O--(CH 2 ) p --O-- where p is 2, 3 or 4 and R 10 is as previously defined; Z represents O, S or ═NR 13 or wherein R 13 represents --CN or R 10 as previously defined; and R may be taken in combination with R 5 , R 6 , R 7 or R 8 as defined above, or R represents H, aryl, alkyl, --SR 11 , --N(R 10 ) 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 3 and R 4 are as previously defined and W is O, S or NR 10 wherein R 10 is as defined above, said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R 10 ) 2 , aryl, --CO 2 R 10 , --OR 12 , --SR 12 , --N(R 10 ) 2 , --N(R 10 )CO 2 R 10 , --COR 12 , --NO 2 or --D, wherein --D and R 10 are as defined above and R 12 represents R 10 , --(CH 2 ) m OR 10 or --(CH 2 ) q CO 2 R 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 10 ) 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.

Claim 27

A compound having the structural formula IC ##STR231## or a pharmaceutically acceptable salt or solvate thereof, wherein: a represents NR 9 and the remaining b, c and d groups represent CH, or one of b, c or d represents N or NR 9 and the remaining a, b, c and d groups represent CH, where R 9 is O - or --(CH 2 ) n CO 2 H where n is 1 to 3, and wherein said remaining a, b, c and d groups optionally substituted with R 1 or R 2 ; R 1 and R 2 are the same or different and each independently represents halo, --CF 3 , --OR 10 , --COR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --OC(O)R 10 , --CO 2 R 10 , --OCO 2 R 11 , alkynyl, alkenyl or alkyl, which alkyl or alkenyl groups are substituted with halo, --OR 10 or --CO 2 R 10 , said alkenyl group not containing --OH on a carbon containing double bond; R 3 and R 4 are the same or different and each independently represent H, any of the substituents of R 1 and R 2 , or R 3 and R 4 together may represent a saturated or unsaturated C 5 -C 7 ring fused to the benzene ring; R 5 , R 6 , R 7 and R 8 each independently represent H, --CF 3 , --COR 10 , --CO 2 R 10 , alkyl or aryl, which alkyl and aryl are optionally substituted with --OR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --COR 10 , --OCOR 10 , --OCO 2 R 11 , --CO 2 R 10 , --OPO 3 R 10 , or one of R 5 , R 6 , R 7 and R 8 are taken in combination with R as defined below to represent --(CH 2 ) r -- where r is 1 to 4 which is optionally substituted with lower alkyl, lower alkoxy, --CF 3 or aryl, or R 5 is combined with R 6 to represent ═O or ═S, or R 7 is combined with R 8 to represent ═O or ═S; each R 10 independently represents H, alkyl or aryl; R 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 10 , --OR 11 or --OC(O)R 10 , and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H 2 , --(OR 11 ) 2 , alkyl and H, (alkyl) 2 , --H and --OC(O)R 10 , H and --OR 10 , H and halo, dihalo, ═O, aryl and H, ═NOR 10 or --O--(CH 2 ) p --O-- where p is 2, 3 or 4 and R 10 is as previously defined; Z represents O, S or ═NR 13 or wherein R 13 represents --CN or R 10 as previously defined; and R may be taken in combination with R 5 , R 6 , R 7 or R 8 as defined above, or R represents H, aryl, alkyl, --SR 11 , --N(R 10 ) 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 3 and R 4 are as previously defined and W is O, S or NR 10 wherein R 10 is as defined above, said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R 10 ) 2 , aryl, --CO 2 R 10 , --OR 12 , --SR 12 , --N(R 10 ) 2 , --N(R 10 )CO 2 R 10 , --COR 12 , --NO 2 or --D, wherein --D and R 10 are as defined above and R 12 represents R 10 , --(CH 2 ) m OR 10 or --(CH 2 ) q CO 2 R 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 10 ) 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.

Claim 28

A compound as defined in claim 24 wherein Z is O or S.

Claim 29

A compound as defined in claim 24 wherein R represents alkyl, cycloalkyl, alkenyl, aryl or alkyl substituted with OR 12 , SR 12 , N(R 10 ) 2 or COR 12 .

Claim 30

A compound according to claim 26 wherein Z is O.

Claim 31

A compound according to claim 27 wherein R 3 represents halo and R 4 represents hydrogen.

Claim 32

A compound according to claim 28 wherein R 5 , R 6 , R 7 and R 8 represent H.

Claim 33

A compound according to claim 29 wherein A and B represent H 2 .

Claim 34

A compound of formula IC as defined in claim 24 having the name: 8-chloro-11-(1-acetyl-4-piperidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine N-oxide; 1-methyl-8-chloro-11-(1-acetyl-4-piperidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridinium iodide; or

Claim 35

9-difluoro-11-(1-acetyl-4-piperidylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine N-oxide.

Claim 36

9-difluoro-11-(1-acetyl-4-piperidylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine N-oxide.

Claim 37

The compound of claim 24 which is: 8-chloro-11-(1-acetyl-4-piperidylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine N-oxide.

Claim 38

The compound of claim 24 which is: 8-fluoro-11-(1-acetyl-4-piperidine)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine N-oxide; 1-acetyl-4-(8-chloro-5,6-dihydro-3-methyl-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine N-oxide, i.e., ##STR233## 1-acetyl-4-(3,8-dichloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine N-oxide, i.e., ##STR234## 1-acetyl-4-[5,6-dihydro-13H-naphtho[2',3',:5,6]cyclohepta[1,2-b]pyridin-13-ylidene]piperidine N-oxide; 1-acetyl-4-(3-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine N-oxide, i.e., ##STR235## 1-(4-pyridinylcarbonyl)-4-(8-chloro-5,6-dihydro-11H-benzo-[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine N 4 -oxide; 1-acetyl-4-(8-chloro-5,6-dihydro-2-methyl-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine N-oxide, i.e., ##STR236## 1-acetyl-4-(3-bromo-8-chloro-5,6-dihydro-3-methyl-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine N-oxide; 1-acetyl-4-(8-chloro-5,6-dihydro-3-(1,1-dimethylethyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine N-oxide; 1-acetyl-4-(8-bromo-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine N-oxide; 1-acetyl-4-(8-chloro-5,6-dihydro-4-methyl-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine N-oxide; or 1-acetyl-4-(4,8-dichloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine N-oxide.

Claim 39

A pharmaceutical composition comprising a compound of formula IC as defined in claim 24 in combination with a pharmaceutically acceptable carrier.

Claim 40

A method of treating allergy comprising administering a compound of formula IC as defined in claim 24 to a mammal in need of such treatment in an amount effective to treat allergy.

Claim 41

A method of treating inflammation comprising administering to a mammal in need of such treatment an antiinflammatory effective amount of a compound of formula IC as defined in claim 24.

Claim 42

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 1 or R 2 ; R 1 and R 2 are the same or different and each independently represents halo, --CF 3 , --OR 10 , --COR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --OC(O)R 10 , --CO 2 R 10 , --OCO 2 R 11 , alkynyl, alkenyl or alkyl, which alkyl or alkenyl groups are optionally substituted with halo, --OR 10 or --CO 2 R 10 , said alkenyl group not containing --OH on a carbon containing double bond; R 3 and R 4 are the same or different and each independently represents H, any of the substituents of R 1 and R 2 , or R 3 and R 4 together may represent a saturated or unsaturated C 5 -C 7 ring fused to the benzene ring; R 5 , R 6 , R 7 and R 8 each independently represent H, --CF 3 , --COR 10 , --CO 2 R 10 , alkyl or aryl, which alkyl and aryl are optionally substituted with --OR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --COR 10 , --OCOR 10 , --OCO 2 R 11 , --CO 2 R 10 , --OPO 3 R 10 , or one of R 5 , R 6 , R 7 and R 8 are taken in combination with R as defined below to represent --(CH 2 ) r -- where r is 1 to 4 which is optionally substituted with lower alkyl, lower alkoxy, --CF 3 or aryl, or R 5 is combined with R 6 to represent ═O or ═S, or R 7 is combined with R 8 to represent ═O or ═S; each R 10 independently represents H, alkyl or aryl; R 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 10 , --OR 11 or --OC(O)R 10 , and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent --(OR 11 ) 2 , alkyl and H, (alkyl) 2 , --H and --OC(O)R 10 , H and --OR 10 , H and halo, dihalo, ═O, aryl and H, ═NOR 10 or --O--(CH 2 ) p --O-- where p is 2, 3 or 4 and R 10 is as previously defined; Z represents O, S or ═NR 13 or wherein R 13 represents --CN or R 10 as previously defined; and R may be taken in combination with R 5 , R 6 , R 7 or R 8 as defined above, or R represents H, aryl, alkyl, --SR 11 , --N(R 10 ) 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 3 and R 4 are as previously defined and W is O, S or NR 10 wherein R 10 is as defined above, said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R 10 ) 2 , aryl, --CO 2 R 10 , --OR 12 , --SR 12 , --N(R 10 ) 2 , --N(R 10 )CO 2 R 10 , --COR 12 , --NO 2 or --D, wherein --D and R 10 are as defined above and R 12 represents R 10 , --(CH 2 ) m OR 10 or --(CH 2 ) q CO 2 R 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 10 ) 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.

Claim 43

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 1 or R 2 ; R 1 and R 2 are the same or different and each independently represents halo, --CF 3 , --OR 10 , --COR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --OC(O)R 10 , --CO 2 R 10 , --OCO 2 R 11 , alkynyl, alkenyl or alkyl, which alkyl or alkenyl groups are optionally substituted with halo, --OR 10 or --CO 2 R 10 , said alkenyl group not containing --OH on a carbon containing double bond; R 3 and R 4 are the same or different and each independently represents H, any of the substituents of R 1 and R 2 , or R 3 and R 4 together may represent a saturated or unsaturated C 5 -C 7 ring fused to the benzene ring; R 5 , R 6 , R 7 and R 8 each independently represent H, --CF 3 , --COR 10 , --CO 2 R 10 , alkyl or aryl, which alkyl and aryl are optionally substituted with --OR 10 , --SR 10 , --N(R 10 ) 2 , --NO 2 , --COR 10 , --OCOR 10 , --OCO 2 R 11 , --CO 2 R 10 , --OPO 3 R 10 , or one of R 5 , R 6 , R 7 and R 8 are taken in combination with R as defined below to represent --(CH 2 ) r -- where r is 1 to 4 which is optionally substituted with lower alkyl, lower alkoxy, --CF 3 or aryl, or R 5 is combined with R 6 to represent ═O or ═S, or R 7 is combined with R 8 to represent ═O or ═S; each R 10 independently represents H, alkyl or aryl; R 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 10 , --OR 11 or --OC(O)R 10 , and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent --(OR 11 ) 2 , alkyl and H, (alkyl) 2 , --H and --OC(O)R 10 , H and --OR 10 , H and halo, dihalo, ═O, aryl and H, ═NOR 10 or --O--(CH 2 ) p --O-- where p is 2, 3 or 4 and R 10 is as previously defined; Z represents O, S or ═NR 13 or wherein R 13 represents --CN or R 10 as previously defined; and R may be taken in combination with R 5 , R 6 , R 7 or R 8 as defined above, or R represents H, aryl, alkyl, --SR 11 , --N(R 10 ) 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 3 and R 4 are as previously defined and W is O, S or NR 10 wherein R 10 is as defined above, said cycloalkyl, alkyl, alkenyl and alkynyl being optionally substituted with from 1-3 groups selected from halo, --CON(R 10 ) 2 , aryl, --CO 2 R 10 , --OR 12 , --SR 12 , --N(R 10 ) 2 , --N(R 10 )CO 2 R 10 , --COR 12 , --NO 2 or --D, wherein --D and R 10 are as defined above and R 12 represents R 10 , --(CH 2 ) m OR 10 or --(CH 2 ) q CO 2 R 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 10 ) 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.

Claim 44

A compound as defined in claim 37 wherein Z is O or S.

Claim 45

A compound as defined in claim 37 wherein R represents alkyl, cycloalkyl, alkenyl, aryl or alkyl substituted with OR 12 , SR 12 , N(R 10 ) 2 or COR 12 .

Claim 46

A compound according to claim 39 wherein Z is O.

Claim 47

A compound according to claim 40 wherein R 3 represents halo and R 4 represents hydrogen.

Claim 48

A compound according to claim 41 wherein R 5 , R 6 , R 7 and R 8 represent H.

Claim 49

A compound according to claim 42 wherein A and B represent H 2 .

Claim 50

A compound of formula ID as defined in claim 37 having the name: 5-hydroxy-8-chloro-11-(1-acetyl-4-piperidylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine; 5-methyl-8-chloro-11-[1-acetyl-4-piperidylidene]-5H-benzo[5,6]cyclohepta[1,2-b]pyridine; 8-chloro-11-[1-acetyl-4-piperidylidene]-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine-5-one; or 2-[8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one.

Claim 51

A compound of formula ID as defined in claim 37 having the name: 8chloro-11-(1-acetyl-4-piperidylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-6-ol.

Claim 52

A pharmaceutical composition comprising a compound of formula ID as defined in claim 37 in combination with a pharmaceutically acceptable carrier.

Claim 53

A method of treating allergy comprising administering a compound of formula ID as defined in claim 37 to a mammal in need of such treatment in an amount effective to treat allergy.

Claim 54

A method of treating inflammation comprising administering to a mammal in need of such treatment an antiinflammatory effective amount of a compound of formula ID as defined in claim 37.

Claim 55

A compound of claim 1 which is: 8-chloro-11-(1-acetyl-4-piperazinyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine; or 4-[8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-(4-pyridinylcarbonyl)piperazine.