Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-11-15
1998-04-07
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514272, 544311, 544325, 544407, C07D23902, C07D23900, C07D24102, A01N 4354
Patent
active
057365504
DESCRIPTION:
BRIEF SUMMARY
This is a 371 application of PCT/JP95/00937 filed on May 17, 1995.
TECHNICAL FIELD
This invention relates to new pyrimidine derivatives and pharmacologically acceptable acid addition salts and quaternary ammonium salts thereof, as well as a process for the preparation of such pyrimidine derivatives.
More particularly, this invention relates to a new pyrimidine derivative which has a promoting action of the release of acetylcholine in digestive tracts, thus being useful for the treatment of digestive tract disorders derived from chronic gastritis, diabetes mellitus, post-gastrectomy and peptic ulcer and digestive tract diseases including reflux esophagitis, irritable bowel syndrome and spurious ileus and a gastrointestinal prokinetic agent which comprises as an active ingredient the said derivatives.
BACKGROUND ART
The abnormality in function of a gastrointestinal mobility by various causes such as chronic gastritis, diabetes mellitus, post-gastrectomy syndrome, peptic ulcer and others results in the reflux of the gastric content into the esophagus, delayed emptying of the gastric content and the depressed function of the small and large intestines.
This leads to appearance of nausea, vomiting, heartburn, anorexia, abdominal distention, epigastric dysphoria, abdominaglia, constipation and further reflux esophagitis. One cause of the diseases such as irritable bowel syndrome and spurious ileus is considered to be the depression in gastrointestinal motility.
The agents for the treatment of these conditions and diseases include direct cholinergic agent (e.g. Aclatonium Napadisilate) or Dopamine antagonist (e.g. Doperidone). However, it is well known that these known agents have the problems in their effects and side-effects, which include, for example, diarrhea and extrapyramidal syndrome.
It is well known that acetylcholine is the neurotransmitter participating in the control of gastrointestinal motility. Thus, a compound capable of accelerating the release of acetylcholine in digestive tracts may be a gastrointestinal prokinetic agent with more effectiveness and less side effects. In this circumstance, such a compound has been required to elucidate.
DISCLOSURE OF INVENTION
The present inventors have made earnest studies to solve the above problems and found that the pyrimidine derivatives as defined below have prominent promoting action of the release of acetylcholine, thus leading to the completion of the present invention.
More particularly, this invention is concerned with a pyrimidine derivative represented by formula (I) ##STR3## wherein X is O or NR.sup.5 ; Y is O, S or NR.sup.5 wherein R.sup.5 is a hydrogen atom, a C.sub.1 -C.sub.6 alkyl group, a C.sub.1 -C.sub.6 alkylcarbonyl group, an aryl group, an aryl C.sub.1 -C.sub.6 alkyl group, an arylaminocarbonyl group, an aryl C.sub.1 -C.sub.4 alkylaminocarbonyl group, or a C.sub.1 -C.sub.6 alkylaminocarbonyl group; atom, a C.sub.1 -C.sub.6 alkyl group, a C.sub.3 -C.sub.6 cycloalkyl group, an aryl group, a C.sub.3 -C.sub.6 cycloalkyl C.sub.1 -C.sub.4 alkyl group, or an aryl C.sub.1 -C.sub.4 alkyl group; group, a C.sub.3 -C.sub.6 cycloalkyl group, an aryl group, or an aryl C.sub.1 -C.sub.4 alkyl group; -C.sub.6 alkyl group; R.sup.8 is a C.sub. -C.sub.6 alkyl group, an aryl C.sub.1 -C.sub.4 alkyl group, a heteroaryl C.sub.1 -C.sub.4 alkyl group, an aryloxy C.sub.2 -C.sub.6 alkyl group, in which the aryl or heteroaryl moiety may be optionally mono- to tri-substituted with a halogen atom, a C.sub.1 -C.sub.6 alkyl group, a halo C.sub.1 -C.sub.6 alkyl group, a C.sub.1 -C.sub.6 alkoxy group, a C.sub.1 -C.sub.6 alkoxycarbonyl group or a phenyl group, or R.sup.8 represents a group of formulae (II)-(IX) ##STR4## wherein R.sup.10 is a C.sub.1 -C.sub.6 alkyl group, an aryl C.sub.1 -C.sub.6 alkyl group, a heteroaryl C.sub.1 -C.sub.6 alkyl group, an aryloxy C.sub.2 -C.sub.6 alkyl group, a pyrrolidinylcarbonyl C.sub.1 -C.sub.4 alkyl group, in which the aryl moiety may be optionally substituted with a halogen atom, a C.sub.1 -C.sub.6 alkyl group, a halo C.sub.1 -C
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Arai Takeo
Eguchi Haruko
Fukutomi Ruta
Hagihara Koichiro
Inomata Kohei
Ngo Tamthom T.
Nisshin Flour Milling Co. Ltd.
Shah Mukund J.
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