Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-02-03
1996-06-04
Datlow, Philip I.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514212, 514216, 514299, 514304, 514307, 514326, 514414, 514422, 514427, 540480, 540582, 540602, 546112, 546122, 546125, 546148, 546208, 548465, 548517, 548518, 548527, 548560, 548561, C07D207335, C07D40104, C07D40106, C07D40304, C07D40306, A61K 3140, A61K 31445
Patent
active
055232990
DESCRIPTION:
BRIEF SUMMARY
This is the rational stage application at international application PCT/EP93/02030 filed Jul. 29, 1993.
The present invention relates to novel phenylpyrrole derivatives, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, in particular as antipsychotic agents.
European Patent Application No. 241053, describes compounds of the formula: ##STR2## wherein A is an unsaturated 5-membered heterocyclic ring, such as 2,5-pyrrolyl, or 3,5- or 1,4- pyrazolyl; X is a nitrogen or carbon atom; R.sub.1, R.sub.2, R.sub.3 are each hydrogen or alkyl; R.sub.4 is aryl, heteroaryl, arylcarbonyl or heteroaryl-carbonyl;R is selected from a variety of substituents and n is 0-4. The compounds are said to have antipsychotic properties.
European Patent Application No. 259930 describes compounds of the formula: ##STR3## wherein A is an unsaturated 5-membered heterocyclic ring, such as 2,5-pyrrolyl, 1,4-pyrazolyl or 2,5-furyl; R is hydrogen, alkyl or optionally substituted phenyl; R.sup.1 is alkyl, alkenyl or forms a ring with the phenyl group; R.sup.2 is hydrogen, hydroxy or alkoxy; R.sup.3 is selected from a variety of substituents and n is 0-3. These compounds are also said to have and psychotic properties.
We have now found a novel class of 2-phenylpyrroles which have high affinity for dopamine D.sub.3 receptors and thus have potential as antipsychotic agents.
In a first aspect the present invention provides compounds of formula (I): ##STR4## wherein R.sup.1 represents C.sub.1-4 alkyl; and hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkoxyC.sub.1-4 alkyl, C.sub.1-4 alkylsulphonyl, trifluoromethylsulphonyl; optionally substituted arylsulphonyl, optionally substituted heteroarylsulphonyl, optionally substituted aralkylsulphonyl, optionally substituted heteroalkylsulphonyl, nitro, cyano, amino, mono- or di-alkylamino, trifluoromethyl, trifluoromethoxy, hydroxyl, hydroxyalkyl, C.sub.1-4 alkylthio, C.sub.1-4 alkanoyl, C.sub.1-4 alkoxycarbonyl, aminosulphonyl, alkylaminosulphonyl or dialkylaminosulphonyl; or substituted by one or two C.sub.1-4 alkyl groups; and Y represents a group selected from: ##STR5## wherein R.sup.6 and R.sup.7 independently represent hydrogen, C.sub.1-6 alkyl, optionally substituted arylC.sub.1-6 alkyl or optionally substituted heteroarylC.sub.1-6 alkyl; cycloalkylC.sub.1-4 alkyl; and cycloalkylC.sub.1-4 alkyl, optionally substituted arylC.sub.1-4 alkyl or optionally substituted heteroarylC.sub.1-4 alkyl; or R.sup.9 is not piperazine); cycloalkylC.sub.1-4 alkyl, optionally substituted arylC.sub.1-4 alkyl or optionally substituted heteroarylC.sub.1-4 alkyl; and n is 1 to 3;
In the compounds of formula (I) an alkyl group or moiety may be straight or branched. Alkyl groups which may be employed include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, n-pentyl; sec-pentyl, n-hexyl and the like.
Representative aryl groups or moieties present in any of the substituents R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.9 and R.sup.10 in compounds of formula (I) include phenyl, naphthyl, and tetrahydronaphthyl. Suitable examples of heteroaryl groups include both 5 and 6-membered heterocycles containing one or more oxygen, sulphur or nitrogen atoms, such as furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, pyridyl, pyridazyl, pyrimidyl and pyrazyl. Substituents for said aryl and heteroaryl groups include halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkoxyalkyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, hydroxyalkyl, C.sub.1-4 alkanoyl, C.sub.1-4 alkoxycarbonyl, amino and mono- or -dialkylamino.
When--NR.sup.8 R.sup.9 forms a heterocyclic ring, this preferably has from 4 to 10, e.g. 5 to 8 ring members, and it may be fully or partially saturated. The ring may optionally contain a sulphur atom, provided there are at least two methylene groups between the S and N atoms. A heterocyclic ring --NR.sup.8 R.sup.9 may also be bridged, for example by a C.sub.1-3 alkylene chain e.g. a meth
REFERENCES:
patent: 4785010 (1988-11-01), Zoller et al.
patent: 4874770 (1989-10-01), Van Wijngaarden et al.
patent: 5428037 (1995-06-01), Pascal et al.
Journal of Medicinal Chemistry, Ingrid Pettersson, Tommy Liljefors, `Conformational analysis of dopamine D-2 receptor antagonists of the benzamide series in relation to a recently proposed D-2 receptor-interaction model`, vol. 35(13), Jun. 26, 1992, pp. 2355-2363.
Journal of Medicinal Chemistry, Ineke Van Wijngaarden, Chris G. Kruse, Jan A. M. Van der Heyden, Martin T. M. Tulp, `2-Phenylpyrroles as conformationally restricted benzamide analogs. A new class of potential antipsychotics. 2`, vol. 31, No. 10, Oct. 1988, pp. 1934-1940.
Journal of Medicinal Chemistry, Ineke Van Wijngaarden, Chris G. Kruse, Roelof Van Hes, Jan A. M. Van der Heyden, Martin T. M. Tulp, `2-Phenylpyrroles as conformationally restricted benzamide analogs. A new class of potential antipsychotics. 1`, vol. 30, No. 11, 1987, pp. 2099-2104.
Hadley Michael S.
Johnson Christopher N.
Nash David J.
Stemp Geoffrey
Datlow Philip I.
Lentz Edward T.
SmithKline Beecham Plc
Stein-Fernandez Nora
Suter Stuart R.
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