Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1992-06-03
1994-09-13
Bernhardt, Emily
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514253, 514254, 514255, 544295, 544296, 544357, 544360, 544363, 544364, 544366, 544370, 544371, 544392, 544394, A61K 31495, C07D295088, C07D40106, C07D40306
Patent
active
053468961
DESCRIPTION:
BRIEF SUMMARY
This invention relates to piperazine derivatives, to processes for their preparation, to their use and to pharmaceutical compositions containing them. The novel compounds act upon the central nervous system by binding to 5-HT receptors (as more fully explained below) and hence can be used as medicaments for treating human and other mammals.
The novel compounds of the invention are those of general formula ##STR2## and the pharmaceutically acceptable acid addition salts thereof.
In formula (I): or more (lower)alkyl groups, with the proviso that R.sup.1 is not an optionally substituted indolyl radical. means that the radical referred to contains 1 to 6 carbon atoms. Preferably such radicals contain 1 to 4 carbon atoms. Examples of "lower alkyl" radicals are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl and isopentyl.
When used herein "aryl" means an aromatic radical having 6 to 12 carbon atoms (e.g. phenyl or naphthyl) which optionally may be substituted by one or more substituents. For example, when R.sup.1 R.sup.2 is aryl it may be a phenyl or naphthyl radical optionally substituted by one or more lower alkyl, lower alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy, cyclopropylmethoxy), halogen, halo(lower)alkyl (e.g. trifluoromethyl), nitro, amino, (lower)alkylamino, di(lower)alkylamino, phenyl, halophenyl, (lower)alkyl phenyl or (lower)alkoxy phenyl substituents. When R.sup.4 is aryl it may be, for example, a phenyl or naphthyl radical optionally substituted by one or more of the substituents listed above and/or by one or more hydroxy, hydroxy(lower)alkyl (e.g. hydroxymethyl), --CONR.sup.5 R.sup.6 (where R.sup.5 and R.sup.6 are each hydrogen or lower alkyl) or --NHSO.sub.2 (lower)alkyl substituents. Preferably the aryl radical R.sup.4 contains a substituent (e.g. lower alkoxy) in the ortho position. A particularly preferred example of R.sup.4 is o-(lower)alkoxyphenyl (e.g. o-methoxyphenyl ) . The term `heteroaryl` refers to a mono or bicyclic aromatic radical containing one or more hetero ring atoms (e.g. oxygen, nitrogen, sulphur) and which may be optionally substituted by one or more substituents. Preferred examples of substituents for the heteroaryl radicals R.sup.1 and R.sup.2 are given above for the aryl radicals R.sup.1 R.sup.2 while preferred examples of substituents for the heteroaryl radical R.sup.4 are given above for the aryl radical R.sup.4. The heteroaryl radical may for example contain up to 11 ring atoms.
Preferably the heteroaryl radical is a monocyclic radical containing 5 to 7 ring atoms or a bicyclic radical containing 8 to 11 ring atoms. Preferably :he hetero ring contains a nitrogen hetero atom with or without further hetero atoms. Examples of heteroaryl groups R.sup.1 and R.sup.2 are optionally substituted pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl and tetrazolyl. These groups may be connected to the remainder of the molecule via a ring heteroatom or a ring C atom.
Examples of the heteroaryl group R.sup.4 include optionally substituted pyridinyl, pyrimidinyl, pyrazinyl, quinolinyl or isoquinolinyl.
Preferred compounds have the following substituents either independently or in combination:
The compounds of the invention may be prepared by methods known in the art from known starting materials or starting materials that may be prepared by conventional methods.
One method of preparing the compounds of the invention comprises alkylating a piperazine derivative of formula ##STR3## with an alkylating agent providing the group ##STR4##
The alkylating agent may be, for example, a compound of formula ##STR5## where R.sup.1, R.sup.2, R.sup.3, W and A are as defined above and X is a leaving group such as halogen or an alkyl- or aryl-sulphonyloxy group. Alternatively the alkylating agent may be an unsaturated compound of formula ##STR6## (where W is (CH.sub.2).sub.m or O and R.sup.2 is an electron withdrawing group e.g. an optionally substituted 2- or 4-pyridyl, 2- or 4-pyrimidyl or 2-pyrazinyl group) and the compound of formula (V) is reacted with t
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Nishimura et al, Chemical Abstracts, vol. 87, No. 53381 (1977).
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Akopyan, Zh. G., et al., Chem. Abst. 71:13091w (1968).
Vinay, S. et al., Indian J. Pharm. vol. 39 (2), 35-36 (1977).
Kapil, R. S. et al., Indian J. Chem. vol. 4 (4) 177-187 (1966).
Ward Terence J.
Warrellow Graham J.
Bernhardt Emily
John Wyeth & Brother Limited
Seifert Arthur G.
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