Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1991-07-17
1993-08-10
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544285, A61K 31505, C07D23996
Patent
active
052349284
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel quinazoline-3-alkanoic acid derivatives having inhibitory effects on platelet aggregation and aldose reductase activity, their salts, their preparation processes and medicinal drugs containing them.
BACKGROUND TECHNIQUES
Recently, it has been made clear that the platelets and the arachidonic acid metabolites play an important role for the origin of thrombotic diseases such as cardiac infarction and the prevention therefrom, and the development of useful drugs therefor such as inhibitory agent of platelet aggregation is expected. On the other hand, with the diabetic neuropathy and complications of diabetes mellitus, the participation of aldose reductase has been made clear, thus the inhibition of the activity of aldose reductase will be connected with the therapy and the prevention of complications originating from diabetes mellitus.
Compounds having inhibitory effect on platelet aggregation or compounds having inhibitory effect on aldose reductase are widely searched separately. For example, the fact that quinazoline-1-alkanoic acid derivatives have the inhibitory effect on aldose reductase is disclosed in Japanese Unexamined Patent Publication No. Sho 62-96476, No. Hei 1-125322 and No. Hei 1-131164, but these compounds have no inhibitory effect on platelet aggregation. The quinazoline-3-alkanoic acid derivatives of the invention are novel compounds, and any prior art to allow to presume that the compounds of the invention have both the inhibitory effect on platelet aggregation and the inhibitory effect on aldose reductase cannot be found.
The purpose of the invention is to provide useful compounds as medicinal drugs having excellent inhibitory effect on aldose reductase together with strong inhibitory effect on platelet aggregation.
DISCLOSURE OF THE INVENTION
As a result of diligent studies to solve such problem, the inventors have found that quinazoline-3-alkanoic acid derivatives represented by a general formula [I] ##STR3## [Wherein R is hydrogen or a protecting group for carboxyl group, R.sup.1 is a lower alkyl group, alkenyl group, alkynyl group, lower alkoxy group, lower alkylthio group, halogen, phenyl group (this phenyl group may be substituted by one to three of lower alkyls, lower alkoxys, halogens, trifluoromethyls, carboxyethylenes or ethoxycarbonylethylenes), naphthyl group, heterocycles (these heterocycles may be substituted by one to three of lower alkyls), cycloalkyl group or benzoyl group (this benzoyl group may be substituted by lower alkyl or halogen), R.sup.2 and R.sup.3 are identically or differently hydrogens, halogens, lower alkyl groups, lower alkoxy groups, aralkyl groups which may be substituted, nitro groups, imidazolyl groups, imidazolylmethyl groups or ##STR4## (R.sup.4 and R.sup.5 indicate identically or differently hydrogens or lower alkyl groups, or connected with each other to make five- or six-membered heterocycles which may contain other hetero atom, X is carbonyl, thiocarbonyl or methylene group (this methylene group may be substituted by lower alkyl group), A is lower alkylene or lower alkenylene, and n indicates an integer of 1 to 3], strong inhibitory effect on aldose reductase, leading to the completion of the invention.
As "lower alkyl" shown in the invention, straight chain or branched one with carbon atoms of 1 to 6 such as methyl, ethyl, n-propyl or isopropyl can be mentioned. As "lower alkoxy", one with carbon atoms of 1 to 3 such as methoxy, ethoxy, n-propoxy or isopropoxy can be mentioned. As "lower alkylthio", one with carbon atoms of 1 to 3 such as methylthio, ethylthio or n-propylthio can be mentioned. As "halogen", fluorine, chlorine, bromine or iodine can be mentioned.
As "five-membered or six-membered heterocycle combined R.sup.4 and R.sup.5 one another, which may contain additional hetero atoms", for example, pyrrolidinyl, piperidino, morpholino, thiazolidyl, imidazolyl, etc. can be mentioned. "Cycloalkyl" means an alicyclic hydrocarbon with carbon atoms of 3 to 6 and, for example, cyclopro
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Fujimori Shizuyoshi
Hirata Yoshihiro
Murakami Koji
Ohnota Michiro
Grumbling Matthew V.
Kyorin Pharmaceutical Co. Ltd.
Shah Mukund J.
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