Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-05-03
1998-10-27
Jarvis, William R. A.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514210, 5142358, 514252, 514255, A61K 3155, A61K 31395, A61K 31535, A61K 31495
Patent
active
058278478
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB93/02197, filed Oct. 25, 1993.
This invention relates to the use of certain piperazine derivatives in the treatment of cognitive disorders
The piperazine derivatives are those of general formula ##STR2## and the pharmaceutically acceptable acid addition salts thereof
In formula (I)
R is hydrogen or lower alkyl,
R.sup.1 an aryl or nitrogen containing heteroaryl radical,
and X is a group of formula
n is one of the integers 1 or 2,
R.sup.2 is hydrogen or lower alkyl,
R.sup.3 is an aryl radical or an aryl(lower)alkyl radical,
R.sup.4 is hydrogen or lower alkyl,
R.sup.5 is hydrogen, an alkyl group of 1 to 8 carbon atoms, cycloalkyl of 3 to 12 carbon atoms or cycloalkyl(lower)alkyl,
or R.sup.4 and R.sup.5 together with the nitrogen atom to which they are attached represent an azetidino, pyrrolidino, piperidino, hexahydroazepino, morpholino or piperazino ring which may be optionally substituted by lower alkyl, aryl or aryl(lower)alkyl,
A is an alkylene chain of 2 to 4 carbon atoms optionally substituted by one or more lower alkyl groups,
R.sup.6 is a mono or bicyclic heteroaryl radical
and R.sup.7 is hydrogen, lower alkyl, cycloalkyl, cycloalkenyl, cycloalkyl(lower)alkyl, aryl, aryl(lower)alkyl, heteroaryl, R.sup.9 is hydrogen, lower alkyl, aryl or aryl(lower)alkyl and R.sup.10 is hydrogen, lower alkyl, --CO(lower)alkyl, aryl, COaryl, aryl(lower)alkyl, cycloalkyl or cycloalkyl(lower)alkyl or R.sup.8 and R.sup.9 together with the nitrogen atom to which they are both attached represent a saturated heterocyclic ring which may contain a further hetero atom! or a group of cycloalkyl(lower)alkyl, aryl, aryl(lower)alkyl, heteroaryl or heteroaryl(lower)alkyl!.
Preferred compounds of formula I are those of ##STR3## or the pharmaceutically acceptable acid addition salts thereof (where n, R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined above).
The term "lower" as used herein 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, tert-butyl, pentyl and isopentyl. Examples of cycloalkyl groups are cyclopentyl, cyclohexyl and cycloheptyl. A preferred example is cyclohexyl. Cycloalkyl groups include bicyclic, tricyclic and tetracyclic groups, e.g. adamantyl. Preferably the cycloalkyl group contains 3 to 12 carbon atoms.
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. Preferred substituents are lower alkyl, lower alkoxy (e.g. methoxy, ethoxy, propoxy, butoxy), halogen, halo(lower)alkyl (e.g. trifluoromethyl), nitro, nitrile, amido, (lower)alkoxycarbonyl, amino, (lower)alkylamino or di(lower)alkylamino substituents. Two substituents on the aromatic ring may be connected together to form another ring system.
When R.sup.1 is an aryl radical it is preferably a phenyl radical containing a substituent in the ortho position. A preferred example of R.sup.1 is o-(lower)alkoxyphenyl e.g. o-methoxyphenyl. R.sup.1 can also be, for example a 1-naphthyl radical optionally substituted in the 2 or 7 positions by, for example, (lower)alkoxy.
Preferred examples of aryl(lower)alkyl are benzyl and phenethyl in which the phenyl rings may be substituted by substituents as given above.
When used herein "nitrogen containing heteroaryl radical" means an aromatic ring containing one or more nitrogen atoms as heteroatoms (e.g. pyridinyl, pyrimidinyl or pyrazinyl) which may optionally be substituted by one or more lower alkyl, lower alkoxy, halogen, trifluoromethyl, amino, (lower)alkylamino or di(lower)alkylamino substituents. Preferably the heteroaryl radical is monocyclic.
When R.sup.6 is a bicyclic heteroaryl radical both rings of the radical may contain hetero ring atoms or only one ring may contain a hetero atom or atoms. In the latter instance the radical R.sup.6 is connected to the rest of the molecule of formula (I) via the ring containi
REFERENCES:
patent: 4423049 (1983-12-01), Temple
patent: 4921958 (1990-05-01), Abou-Gharbia et al.
patent: 4988814 (1991-01-01), Abou-Gharbia et al.
Costall, B. et al., Pharmacopsychiatry 23/SU 2:85-89 (1990).
Murphy, D. L., Neuropsychopharmacology 3:457-471 (1990).
Rydelek-Fitzgerald, L. et al., Brain Research 532:191-196 (1990).
Winter, J. C. et al., Pharmacology Biochemistry & Behavior 27:625-628 (1987).
Hunter, A. J. et al., Behavioural and Neurochemical Pharmacology 22:278-285, 1987.
Ogren, S. O., Biology of Seortonergic Transmission 13:317-334 (1982).
Cliffe Ian Anthony
Fletcher Allan
White Alan Chapman
Jarvis William R. A.
John Wyeth & Brother Ltd.
Seifert Arthur G.
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