Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1999-03-10
2000-05-16
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
546166, 546178, 546181, 546157, 544353, 514311, 514312, C07D21500, C07D21528, C07D21520, A61K 3147, A61K 31495
Patent
active
060637846
DESCRIPTION:
BRIEF SUMMARY
5-HT.sub.1A ligands may be useful for the treatment of anxiety, depression and hypertension (Brain 5-HT.sub.1A Receptors: Behavioural and Neurochemical Pharmacology; Editors C. T. Dourish, S. Ahlenius, P. H. Huston; Ellis Horwod LTD, Chischester (1987)).
It has also been shown that 5-HT.sub.1A ligands inhibit the secretion of gastric acid (D. C. Evans, J. S. Gidda, Gastroenterology, 104, A76 (1993)), exhibit anti-emetic effects (F. Okada, Y. Torii, H. Saito, N. Matsuki, Jpn. J. Pharmacol., 64, 109 (1994)) and act on the motility of the gastrointestinal system (Serotonin and Gastrointestinal Function, Editors T. S. Gaginella, J. J. Galligan; CRC Press, Boca Raton (1995)).
The present invention relates to new heteroaryloxyethylamines having a high affinity for the 5-HT.sub.1A receptor, a process for the preparation thereof, pharmaceutical compositions containing them, and their use particularly as inhibitors of gastric acid secretion or as anti-emetics.
A subject of the invention is, therefore, products corresponding to general formula I ##STR2## in which Ar represents a bicyclic heteroaryl, optionally substituted by one or more substituents; one or more lower alkyl(s); or a phenyl optionally substituted by one or more substituents chosen from the hydroxy, cyano, halo, trifluoromethyl, lower alkyl, lower alkoxy radicals;
More particularly, a subject of the invention is the products corresponding to general formula I as defined above, characterised in that Ar represents a bicyclic heteroaryl radical containing one or two nitrogen atoms, and the substituent(s) which the radical which Ar represents may bear are chosen from the hydroxy, nitro, halo, lower alkyl, lower alkoxy, lower alkyl carbonyl radicals.
In the definitions given above, the expression halo represents fluoro, chloro, bromo or iodo and preferably chloro. The expression lower alkyl represents a linear or branched alkyl radical having 1 to 6 carbon atoms, such as the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl and hexyl radicals.
The cycloalkyl radicals may be chosen from saturated monocyclic radicals having 3 to 7 carbon atoms such as the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl radicals.
The lower alkoxy radicals may correspond to the lower alkyl radicals indicated above. Methoxy, ethoxy or isopropyloxy radicals are preferred.
The bicyclic heteroaryl radicals containing one or two nitrogen atoms may be chosen from the radicals corresponding to the compounds indole, indazole, isoquinoline, quinoline, quinoxaline and quinazoline.
The products corresponding to formula I may form addition salts with acids, particularly pharmacologically acceptable acids.
Examples of salts are given below in the experimental part.
More particularly, a subject of the invention is the products corresponding to general formula I as defined above, characterised in that Ar represents the quinolyl or quinoxalinyl radical, and the substituent(s) which the radical represented by Ar may bear are chosen from the hydroxy, chloro, methyl radicals.
More particularly, a subject of the invention is the products described below in the examples, particularly the products corresponding to the following formulae:
The invention also provides a process for the preparation of the products corresponding to general formula I as defined above, characterised in that ##STR3## in which Y and R have the meaning given above and X represents a halogen or a pseudo halogen, is allowed to react with N-benzylethanolamine corresponding to the formula ##STR4## in order to obtain a product corresponding to formula III ##STR5## which is converted to a product corresponding to formula IV ##STR6## in which Z represents a halogen or a pseudo halogen, which product corresponding to formula IV is converted to a product corresponding to formula V ##STR7## in which Ar has the meaning given above, the benzyl function of which product corresponding to formula V is cleaved in order to obtain the product corresponding to formula I, and which p
REFERENCES:
Ross, Chapter 2 in Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th Ed., Pergamon Press, P.33-35, 1991.
Brayer et al. Chem. abstract 114:121758, Nov. 1991.
Chilmonczyk et al Buspirone . . . Analogues, Journal of Medicinal Chemistry, vol. 38, No. 10, May 12, 1995, pp. 1701-1710.
Hibert et al, Graphics . . . Receptor, Journal of Medicinal Chemistry, vol. 31, No. 6, 1988, pp. 1087-1093.
Bigg Dennis
Galcera Marie-Odile
Liu Hong
Raymond Richard L.
Societe de Conseils de Recherches et D'Applications Scientifique
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