Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Patent
1999-03-11
1999-12-07
Killos, Paul J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
564167, 564 51, 560 39, 514620, C07C23300
Patent
active
059986662
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 Horwood 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 derivatives of phenoxyethylamine having a high affinity for the 5-HT.sub.1A receptor, processes for their preparation, pharmaceutical compositions containing them, and their use as medicaments, particularly as inhibitors of gastric acid secretion or as anti-emetics.
A subject of the invention is, therefore, products corresponding to general formal I ##STR1## in which Ar represents a phenyl substituted by one or more substituents; from linear or branched alkyl, or cycloalkyl radicals;
More particularly, a subject of the invention is the products corresponding to general formula I as defined above, characterised in that the substituent(s) which the phenyl radical represented by Ar may bear are chosen from the lower alkoxy, --C(O)NR.sub.1 R.sub.2, --NHC(O)R.sub.3, --NHC(O)NR.sub.4 R.sub.5, --NHC(O)OR.sub.6 radicals, in which R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 represent, independently, a hydrogen atom or a lower alkyl, and R.sub.6 represents a lower alkyl.
In the definitions given above, the expression lower alkyl represents preferably a linear or branched alkyl radical having 1 to 6 carbon atoms, such as the methyl, ethyl, propyl, isopropyl, butyl, isobtuyl, 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 cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl radicals.
The lower alkoxy radicals may correspond to the lower alkyl radicals indicated above. Methoxy, ethoxy or isopropyloxy radicals are preferred.
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.
A subject of the invention is in particular compounds corresponding to general formula I as described above, characterised in that Ar represents a phenyl radical substituted by a substituent chosen from the methoxy, --C(O)NHMe, --NHC(O)Me, --NHCONH.sub.2, --NHCONHMe, NHC(O))Me radicals, and in that R represents the tert-butyl, neopentyl, cyclopentyl, cyclohexyl or cycloheptyl radical.
The substituents of the phenyl radical which Ar may represent are preferably situated in position 2 or 3.
More particularly, a subject of the invention is the products described below in the examples, particularly the products corresponding to the following formulae: and the salts of said compounds with inorganic or organic acids.
The invention also provides a process for the preparation of products corresponding to general formula I as defined above, characterised in that
A) either a product corresponding to formula II ##STR2## in which Ar has the meaning given above, is allowed to react with a product corresponding to formula III ##STR3## in which X represents a halogen or a pseudo halogen, in order to obtain a product corresponding to formula IV ##STR4## which product corresponding to formula IV is treated with an amino corresponding to the formula RNH.sub.2 in which R has the meaning given above, in order to obtain a product corresponding to formula V. ##STR5## which product corresponding to formula V is converted to a product corresponding to formula I by cleavage of the benzyl function, and which product corresponding to formula I may be converted to acid salts by the action of the correspon
REFERENCES:
patent: 5585492 (1996-12-01), Chandrakumar
Shutske, "Recent . . . Pharmacology", Expert Opinion on Therapeutic Patents, vol. 4, No. 10, Oct. 1, 1994, pp. 1233-1242.
Glennon, "Concepts . . . Antagonists", Drug Development Research, vol. 26, No. 3, Jan. 1, 1992 pp. 251-274.
Okada et al "Antiemetic . . . Suncus Murinus", The Japanese Journal of Pharamacology, vol. 64, No. 2, Feb. 2, 1994, pp. 109-114.
Bigg Dennis
Galcera Marie-Odile
Killos Paul J.
Societe de Conseils de Recherches Et d'Applications Scientifique
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