Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-08-15
1998-12-29
Powers, Fiona T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514326, 546196, 546209, A61K 31445, C07D41304
Patent
active
058542612
DESCRIPTION:
BRIEF SUMMARY
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a 371 based upon PCT Application Serial No. PCT/EP96/00784, filed Feb. 21, 1996, which claims priority from European Patent Application Serial No. 95.200.501.5, filed on Mar. 1, 1995.
The present invention concerns novel prokinetic oxadiazole derivatives. It further relates to pharmaceutical compositions comprising them, processes for preparing said compounds and compositions, and the use thereof as a medicine, in particular in the conditions involving a decreased motility of the colon.
EP-0,076,530, EP-0,389,037 and EP-0,445,862 disclose N-(4-piperidinyl)benzamide derivatives having gastrointestinal motility stimulating properties. WO-94/12494 describes the use of dimethylbenzofurans and dimethylbenzopyrans as 5-HT.sub.3 antagonists. WO 93/02677 describes oxadiazoles as 5-HT.sub.4 receptor antagonists. WO 94/08994 describes a number of 1 -butyl-4-piperidinylmethyl substituted bicyclic benzoic ester derivatives as 5-HT.sub.4 receptor antagonists. WO 94/08995 describes some other 1-butyl-4-piperidinylmethyl substituted bicyclic benzoic ester derivatives as 5-HT.sub.4 receptor antagonists. WO 94/10174 discloses N-piperidinyl (benzodioxolane and 1,4-benzodioxane)carboxamide derivatives as 5-HT.sub.4 receptor antagonists.
The compounds of the present invention differ from the prior art compounds by the presence of an oxadiazole moiety which is directly bound to the piperidinyl ring. The present compounds unexpectedly show favourable intestinal motility stimulating properties. More in particular, they show motility enhancing effects on the colon.
This invention concerns compounds of formula ##STR3## the N-oxide forms, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein: radical wherein one or two hydrogen atoms may be replaced by C.sub.1-4 alkyl; ##STR4## L is a radical of formula: alkylsulfmyl, C.sub.1-6 alkylsulfonyl, aryl, arylcarbonyl, tetrahydrofuran, dioxolane, dioxolane substituted with C.sub.1-6 alkyl, dioxane, dioxane substituted with C.sub.1-6 alkyl; C.sub.1-6 alkylcarbonyl; substituents selected from halo, C.sub.1-6 alkyl or C.sub.1-6 alkyloxy.
As used in the foregoing definitions halo is generic to fluoro, chloro, bromo and iodo; C.sub.1-4 alkyl defines straight and branched saturated hydrocarbon radicals having from 1 to 4 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylethyl, 2-methylpropyl and the like; C.sub.1-6 alkyl defines C.sub.1-4 alkyl and the higher homologues having 5 or 6 carbon atoms such as, for example, pentyl, hexyl and the like; C.sub.2-6 alkenyl defines straight or branched hydrocarbon radicals having 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-methyl-2-butenyl and the like; C.sub.2-6 alkynyl defines straight or branched hydrocarbon radicals having one triple bond and having 2 to 6 carbon atoms such as, for example, ethynyl, 2-propynyl, 3-butynyl, 2-butynyl, 2-pentynyl, 3-methyl-2-butynyl and the like; C.sub.2-3 alkanediyl defines bivalent straight or branched hydrocarbon radicals containing from 2 to 3 carbon atoms such as, for example, 1,2-ethanediyl, 1,3-propanediyl and the like; C.sub.1-12 alkanediyl defines C.sub.2-3 alkanediyl, the lower homologue, i.e. 1,1-methanediyl, and the higher homologues having from 4 to 12 carbon atoms such as, for example, 1,4-butanediyl, 1,5-pentanediyl, 1,6-hexanediyl, 1,7-heptanediyl, 1,8-octanediyl, 1,9-nonanediyl, 1,10-decanediyl, 1,11-undecanediyl, 1,12-dodecanediyl and the branched isomers thereof.
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 a
REFERENCES:
International Search Report Application Number PCT/EP96/00784.
Patent Abstracts of Japan, Vol. 18, No. 485(C-1248) Sep. 9, 1994 & JP A 06 157518 (Yamanouchi Pharmaceut Co Ltd), Jun. 3, 1994 in connection with Chemical Abstracts, 1994 Vol. 121 No. 23, p. 1035, No. 280649k.
Chemical Abstracts, 1994 Vol. 121, Chemical Substance Index, part 1 p. 1073cs, col. 3, lines 57-61.
Ciambrone Coletti Ellen
Janssen Pharmaceutica N.V.
Powers Fiona T.
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