Phenyl-oxo-alkyl-(4-piperidinyl)benzoate derivatives

Details Phenyl-oxo-alkyl-(4-piperidinyl)benzoate derivatives Phenyl-oxo-alkyl-(4-piperidinyl)benzoate derivatives

1997-03-24

1999-02-16

Kight, John

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514327, 546196, 546218, A61K 31445, C07P21144

Patent

active

058721312

DESCRIPTION:

BRIEF SUMMARY
CROSS-REFERENCE TO RELATED APPLICATIONS

This application is the national stage of application No. PCT/EP 95/03690, filed on Sep. 19, 1995, which application claims priority from EP 94.202.791.3, filed on Sep. 27, 1994.
The present invention is concerned with novel benzoate derivatives, pharmaceutical compositions comprising said novel compounds, processes for preparing compounds and compositions, and the use thereof as a medicine, in particular in the treatment of conditions involving a decreased motility of the colon.
In our EP-0,389,037-A, published on Sep. 26, 1990, N-(3-hydroxy-4-piperidinyl) (dihydrobenzofuran or dihydro-2H-benzopyran)carboxamide derivatives are disclosed as having gastrointestinal motility stimulating properties. In our EP-0,445,862-A, published on Sep. 11, 1991, N-(4-piperidinyl) (dihydrobenzofuran or dihydro-2H-benzopyran)carboxamide derivatives are disclosed also having gastrointestinal motility stimulating properties. WO 93/03725 (SmithKline Beecham), published on Mar. 4, 1993, generically discloses the use as 5HT.sub.4 receptor antagonists of esters of general formula X--CO--Y--Z, wherein X can be a substituted phenyl, Y can be oxygen, and Z can be a substituted piperidine moiety. WO 94/08995 (SmithKline Beecham), published on Apr. 28, 1994 generically discloses, for instance, substituted 7-benzofuran carboxylates also having 5HT.sub.4 antagonistic activity. The latter two patent applications describe the use of the 5HT.sub.4 antagonistic compounds in the treatment of irritable bowel syndrome (IBS), in particular the diarrhoea aspects of IBS.
Unexpectedly, we have discovered that the present novel compounds show intestinal prokinetic activity. Hence, the presently disclosed compounds show utility in treatment of conditions involving a decreased motility of the intestine, especially the colon.
The present invention is concerned with novel benzoate derivatives having the formula ##STR2## the N-oxide forms, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein: alkenyl or C.sub.2-6 alkynyl; or atoms may be replaced by C.sub.1-6 alkyl; C.sub.1-6 alkyl, C.sub.1-6 alkyloxy; formula: ##STR3## R.sup.8 and R.sup.9 each independently are hydrogen or C.sub.1-6 alkyl; R.sup.10 is hydrogen, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkyloxycarbonyl; and
As used in the foregoing definitions and hereinafter, halo is generic to fluoro, chloro, bromo and iodo; C.sub.1-6 alkyl defines straight and branched chain saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, 1-methylethyl, 2-methylpropyl and the like; C.sub.2-6 alkenyl defines straight and branched chain hydrocarbon radicals containing one double bond and having from 2 to 6 carbon atoms such as, for example, ethenyl, 2-propenyl, 3-butenyl, 2-butenyl, 2-pentenyl, 3-pentenyl, 3-methyl-2-butenyl, 3-hexenyl, and the like; C.sub.2-6 alkynyl defines straight and branched chain hydrocarbon radicals containing one triple bond and having from 2 to 6 carbon atoms such as, for example, ethynyl, 2-propynyl, 3-butynyl, 2-butynyl, 2-pentynyl, 3-pentynyl, 3-hexynyl and the like; C.sub.1-6 -alkanediyl defines bivalent straight or branched chain hydrocarbon radicals containing from 1 to 6 carbon atoms such as, for example, methylene, 1,2-ethanediyl, 1,3-propanediyl, 1,4-butanediyl, 1,5-pentanediyl, 1,6-hexanediyl.
The pharmaceutically acceptable acid addition salts as mentioned hereinabove are meant to comprise the therapeutically active non-toxic acid addition salt forms which the compounds of formula (I) are able to form. The latter can conveniently be obtained by treating the base form with such appropriate acid. Appropriate acids comprise, for example, inorganic acids such as hydrohalic acids, e.g. hydrochloric or hydrobromic acid; sulfuric; nitric; phosphoric and the like acids; or organic acids such as, for example, acetic, propanoic, hydroxyacetic, lactic, pyruvic, oxalic, malonic, succinic, maleic, fumaric, malic, tartaric, c

REFERENCES:
patent: 4853394 (1989-08-01), King
patent: 5130312 (1992-07-01), Van Daele
patent: 5262418 (1993-11-01), Van Daele
patent: 5374637 (1994-12-01), Van Daele
Ohshiko et al. "Effect of Y-25130 on gastrointestinal . . . " Japan. J. Phar. v.61 suppl. 195p (p-61) 1993.
Stedman's "Medical Dictionary" Williams and Wilkins p. 533 1995.
Ohshiko, "Effect of Y-25130 on Gastrointestinal. . .", Japanese Journal of Pharmacology, vol 61, supplement I, pp. 61, 1993.
Stedman, Stedman's Medical Dictionary, pp. 533, 1995.

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