Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1993-04-07
1995-05-16
Tsang, Cecilia
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514254, 514318, 544360, 544361, 546193, 546194, A61K 3144, A61K 31495, C07D40112, C07D40106
Patent
active
054160871
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to bis-benzo cyclohepta piperidine, piperidylidene and piperazine compounds and to pharmaceutical compositions and methods of using such compounds.
U.S. Pat. Nos. 3,326,924, 3,717,647 and 4,282,233, European published Application No. 0042544, Villani et al., Journal of Medicinal Chemistry, Vol. 15, No. 7, pp 750-754 (1972) and Arzn. Forsh 36 1311-1314 (1986) describe certain 11-(4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridines as antihistamines. U.S. Pat. No. 4,355,036 describes certain N-substituted piperidylidene compounds.
WO 88/03138 discloses compounds of the formula ##STR2## 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, --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 may be substituted with R.sup.1 or R.sup.2 ; 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 group may be substituted with halo, --OR.sup.10 or --CO.sub.2 R.sup.10 ; 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 fused C.sub.5 -C.sub.7 ring; --CF.sub.3, alkyl or aryl, which alkyl or aryl may be 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 may be taken in combination with R as defined below to represent --(CH.sub.2).sub.r -- where r is 1 to 4 which may be substituted with lower alkyl, lower alkoxy, --CF.sub.3 or aryl; ##STR3## which C may contain an optional double bond to carbon atom 11; 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: 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, ##STR4## 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, with from 1-3 groups selected from --halo, --CON(R.sup.10) --aryl, --CO.sub.2 R.sup.10, --OR.sup.12, --SR.sup.12, --N(R.sup.10).sub.2, --N(R.sup.10)COR.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 COR.sup.10 wherein R.sup.10 is as previously defined, m is 1 to 4 and q is 0 to 4, --N(R.sup.10).sub.2 on a carbon containing a double or triple bond respectively groups above, aryloxy or alkoxy; and or --E--OR.sup.12 where E is alkanediyl which may be substituted with --OR.sup.10, --SR.sup.10, --N(R.sup.10).sub.2 or --D where D, R.sup.10 and R.sup.12 are as previously defined. These compounds are disclosed as being useful in the treatment of allergy and inflammation.
SUMMARY OF THE INVENTION
We have now unexpectedly found that compounds having the structural formula I below provide surprisingly good activity as PAF antagonists and as antihistamines. In particular, we have discovered such characteristics in compounds represented by the structural formula I ##STR5## or a pharmaceutically acceptable salt or solvate thereof, wherein: L represents N or N.sup.+ O.sup.- ; ##STR6## m and n are integers 0, 1, 2 or 3 such that the sum of m plus n equals 0 to 3; or 2, --NR.sup.14 --, --C(O)NR.sup.14 --, --NR.sup.14 C(O)--, --C(S)NR.sup.14 --, --NR.sup.14 C(S)--, --CO.sub.2 -- or --O.sub.2 C--, where R.sup.14 is as defined below; or 2, or --NR.sup.14 ; equalling 1 and
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patent: 4355036 (1982-10-01), Villani
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Arzneim.-Forsch/Drug Research 36 II No. 9, pp. 1311-1314 (1986).
Journal of Medicinal Chemistry, vol. 15, No. 7, pp. 750-754 (1972).
Green Michael J.
Piwinski John J.
Wong Jesse K.
Mazer Edward H.
Tsang Cecilia
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