Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1993-04-01
1995-07-11
Tsang, Cecilia
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514255, 514318, 514326, 514360, 514364, 514369, 546193, 546194, 546209, 546210, 546212, 546225, 546241, 546243, 548200, A61K 31495, A61K 31445, C07D40106, C07D41706
Patent
active
054321751
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to pyridine and pyridine N-oxide derivatives of diaryl methyl piperidines or piperazines and to pharmaceutical compositions and methods of using such compounds.
European Patent Application No. 0 113 226 discloses benzhydrylpiperazine derivatives of the formula: ##STR1## wherein
A is lower alkylene,
Z is benzhydryl optionally substituted with halogen, and
R.sup.1 is amino, aryl, pyridyl, acyl or acylamino, in which the aryl group and pyridyl group are substituted with nitro, amino or acylamino, provided that Z is benzhydryl substituted with halogen, when R.sup.1 is amino, and pharmaceutically acceptable salts thereof. These compounds are said to possess anti-allergic activities. Other similar piperazine compounds are disclosed in South African published Patent Application Nos. 864522 and 864458 and in European Patent Application No. 0 283 310.
SUMMARY OF THE INVENTION
We have now unexpectedly found that compounds represented by the structural formula 1.0 below have good activity as PAF antagonists and antihistamines: ##STR2## or a pharmaceutically acceptable salt or solvate thereof, wherein:
Ar.sup.1 represents ##STR3##
Ar2 represents ##STR4## or a five-membered heterocyclic aromatic group containing at least one ##STR5## in the ring structure, wherein the substitutable carbon atoms of the five-membered heterocyclic group may optionally be substituted with a group R.sup.1 as defined below;
one of a, b, c, d and e represents N or NO and the others represent CH or CR.sup.1 or all of a, b, c, d and e represent CH or CR.sup.1 ;
one of f, g, h, i and k represents N or NO and the others represent CH or CR.sup.2 or all of f, g, h, i and k represent CH or CR.sup.2 ;
L represents N or N.sup.+ O.sup.- ;
R.sup.1 and R.sup.2 may be the same or different and each R.sup.1 and each R.sup.2 independently represents halo, --CF.sub.3, --OR.sup.11, --C(O)R.sup.11, --SR.sup.11, --S(O).sub.e R.sup.12 where e is 1 or 2, --N(R.sup.11).sub.2, --NO.sub.2, --OC(O)R.sup.11, --CO.sub.2 R.sup.11, --OCO.sub.2 R.sup.12, --CON(R.sup.11).sub.2, --NR.sup.11 C(.dbd.O)R.sup.11, --CN, alkyl, aryl, alkenyl or alkynyl, which alkyl group may be substituted with --OR.sup.11, --SR.sup.11, --N(R.sup.11).sub.2 or --CO.sub.2 R.sup.11 and which alkenyl group may be substituted with halo, --OR.sup.12 or --CO.sub.2 R.sup.11 ;
in addition, two adjacent R.sup.1 groups on ring t may together form a benzene ring fused to the ring t and/or two adjacent R.sup.2 groups on ring s may together form a benzene ring fused to the ring s;
R.sup.5 and R.sup.6 may be the same or different and each independently represents H, alkyl or aryl, which alkyl may be substituted with --OR.sup.11, --SR.sup.11 or --N(R.sup.11).sub.2 ;
in addition, R.sup.5 and R.sup.6 together on the same carbon atom may represent .dbd.O or .dbd.S;
each of R70 R.sup.8 and R9 independently represents H, halo, --CF.sub.3, --OR.sup.11, --C(O)R.sup.11, SR.sup.11, --S(O).sub.e R.sup.12 where e is 1 or 2, --N(R.sup.11).sub.2, --NO.sub.2, --CN, --CO.sub.2 R.sup.11, --OCO.sub.2 R.sup.12, --OC(O)R.sup.11, --CON(R.sup.11).sub.2, --NR.sup.11 C(O)R.sup.11, alkyl, aryl, alkenyl or alkynyl, which alkyl group may be substituted with --OR.sup.11, --SR.sup.11, --N(R.sup.11).sub.2, or --CO.sub.2 R.sup. 11 and which alkenyl group may be substituted with halo, --OR.sup.12 or --CO.sub.2 R.sup.11 ;
R.sup.10 represents H or alkyl;
each R.sup.11 independently represents H, alkyl or aryl;
each R.sup.12 independently represents alkyl or aryl;
T represents CH, C or N, with the dotted lines attached to T representing one double bond in one of the indicated positions when T is C and being absent when T is CH or N; and
Z represents O or S, or Z may optionally represent H and R.sup.10 when (a) L represents N.sup.+ O.sup.-, or (b) Ar.sup.2 represents a five-membered heterocyclic aromatic group, or (c) T represents C or CH.
In a preferred embodiment of the invention, the compound of the invention is of the formula 1.1: ##STR6## where a, b, c, d, e, f, g, h, i, k, T, Z,
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Friary Richard
Green Michael J.
Piwinski John J.
Seidl Vera
Wong Jesse
Jeanette Henry C.
Nelson James R.
Schering Corporation
Tsang Cecilia
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