Quinoline derivatives

Details Quinoline derivatives Quinoline derivatives

1997-03-26

1997-12-02

Davis, Zinna Northington

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

514256, 514269, 544333, 546172, 546175, C07D41306, C07D41706, A61K 3147

Patent

active

056936516

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP95/02167 filed Oct. 20, 1995.
Field of the Invention
This invention relates to quinoline derivatives having hypoglycemic effect.
Background of the Invention
Heretofore, treatment of diabetes has been performed using a parenteral injection such as an insulin preparation or an oral antidiabetic such as a biguanide compound (e.g., metoformin) or a sulfonylurea compound (e.g., tolbutamide). The insulin preparation has a disadvantageous problem in its troublesome procedure which is inherent to parenteral injection. The orally administrable biguanide compound brings about unfavorable lactic acidosis, and the sulfonylurea compound gives such side-effect as grave hypoglycemia.
Recently, much attention has been paid to 5-substituted benzylthiazoline-2,4-dione derivatives such as troglitazone (European Patent No. 139,421) and pioglitazone hydrochloride (European Patent No. 193,256) which have no noticeable defects such as above and show new pharmacological mechanism such as curing of defective insulin activity (insulin resistance). It has been reported that pioglitazone shows hypoglycemic activity and neutral fat-reducing effect, cures damaged insulin-receptor function, and gives influence to glucose transporter and glycokinase, so that defective insulin activity can be cured.
The present invention has an object to provide a novel quinoline derivative having hypoglycemic effect.
Particularly, the invention has an object to provide a novel quinoline derivative showing hypoglycemic effect by oral administration.


SUMMARY OF THE INVENTION

The present inventors have studied new thiazolidine-2,4-dione derivatives having no benzyl substituent in their 5-positions and, as a result, have discovered that the quinoline derivatives of the following formula (I) have excellent hypoglycemic activity: ##STR2## in which R.sup.1 represents hydrogen, formula of --NR.sup.4 R.sup.5 in which each of R.sup.4 and R.sup.5 independently is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, pyridyl, pyrimidyl or benzoyl, or atoms, or a 5 to 8 membered heterocyclic group comprising, as ring-constituting atoms, 1 to 2 nitrogens, oxygens or sulfurs and remaining carbon atoms, each of which may have, as a substituent, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, halogen, hydroxyl, halogenoalkyl of 1 to 6 carbon atoms, halogenoalkoxy of 1 to 6 carbon atoms, nitro, amino, phenyl, thienyl, furyl, thiazolyl or pyridyl; or double bond.
The present invention has been completed based on the above-mentioned discovery.
In the quinoline derivatives of the invention, particularly preferred are the quinoline derivatives of the following formula (II): ##STR3## in which R.sup.2 represents hydrogen, formula of --NR.sup.6 R.sup.7 in which each of R.sup.6 and R.sup.7 independently is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, pyridyl, pyrimidyl or benzoyl, or atoms, or a 5 to 8 membered heterocyclic group comprising, as ring-constituting atoms, 1 to 2 nitrogens, oxygens or sulfurs and remaining carbon atoms, each of which may have, as a substituent, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, halogen, hydroxyl, halogenoalkyl of 1 to 6 carbon atoms, halogenoalkoxy of 1 to 6 carbon atoms, nitro, amino, phenyl, thienyl, furyl, thiazolyl or pyridyl; or double bond.
In the quinoline derivatives of the invention, most preferred are the quinoline derivatives of the following formula (III): ##STR4## in which R.sup.3 represents a phenyl group, an oxazolyl group, or a pyridyl group, each of which may have, as a substituent, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, halogen, hydroxyl, halogenoalkyl of 1 to 6 carbon atoms, halogenoalkoxy of 1 to 6 carbon atoms, nitro, amino, phenyl, thienyl, furyl, thiazolyl or pyridyl; and k is an integer of 0 to 4.


PREFERRED EMBODIMENTS OF THE INVENTION

The preferred groups for each symbol seen in the formulas (I), (II), and (III) are described below.
(1) R.sup.1 and R.sup.2 isopropyl); R.sup.7 (R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are the same

REFERENCES:
Chemical Abstracts, vol. 71, No. 13, Abstract No. 61, 742f, Sep. 29, 1969, p. 512.

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