Thiazolidinedione derivatives, production and use thereof

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

546280, A61K 3144, C07D41712

Patent

active

054419719

DESCRIPTION:

BRIEF SUMMARY
This is the national phase application (35 USC 371) of PCT/U.S. Pat. No. 92/02566 filed Apr. 6, 1992.


FIELD OF THE INVENTION

The present invention relates to novel thiazolidinedione derivatives having hypoglycemic and hypolipidemic activities, the production thereof and a pharmaceutical composition for treating diabetes containing them.


BACKGROUND OF THE INVENTION

Various biguanide compounds and sulfonylurea compounds have been used as agents for treating diabetes. However, at present, biguanide compounds are scarcely used because they cause lactic acidosis. Although sulfonylurea compounds have strong hypoglycemic activity, they often cause serious hypoglycemia and they must be used with caution.


OBJECTS OF THE INVENTION

The present inventors have intensively studied to find out compounds having hypoglycemic activity without the above drawbacks. As a result, it has been found novel thiazolidinedione derivatives having excellent hypoglycemic and hypolipidemic activities. Thus, the present invention have been completed.
The main object of the present invention is to provide novel compounds having no above drawbacks of conventional biguanide compounds and sulfonylurea compounds.
This object as well as other objects and advantages of the present invention will become apparent to those skilled in the art from the following description.


SUMMARY OF THE INVENTION

According to the present invention, there is provided a thiazolidinedione derivative of the general formula (I): ##STR2## wherein X is --CH.sub.2 -- or --CO--, Q is CH.sub.3 CO--, CH.sub.3 CH(OR)-- or --CH.sub.2 COOH, when X is --CH.sub.2 --, wherein R is a hydrogen atom or an acyl group, or Q is CH.sub.3 CH.sub.2 --, when X is --CO--, a pharmaceutically acceptable salt thereof, or a pure stereoisomeric form thereof.
The present invention also provide a pharmaceutical composition;for treating diabetes comprising as an effective component the thiazolidinedione derivative of the general formula (I), a pharmacologically acceptable salt thereof or a pure stereoisomeric form thereof.


DETAILED DESCRIPTION OF THE INVENTION

Examples of the acyl group represented by R in the general formula (I) include formyl, alkylcarbonyl having 2 to 6 carbon atoms (e.g., acetyl, propionyl, isobutyryl, pentanoyl, isopentanoyl, hexanoyl, etc.), aralkylcarbonyl having 8 to 9 carbon atoms (e.g., phenylacetyl, phenylpropionyl, etc.), arylcarbonyl having 7 to 8 carbon atoms (e.g., benzoyl, p-toluoyl, etc.) and the like. The aralkylcarbonyl and arylcarbonyl may have one or more substituents such as halogen (fluorine, chlorine, bromine, etc.), lower alkoxy having 1 to 4 carbon atoms (methoxy, ethoxy, etc.), trifluoromethyl and the like.
The thiazolidinedione derivative of the general formula (I) (hereinafter referred to as the compound (I)) possesses an acidic nitrogen atom in the thiazolidine ring and a basic nitrogen atom in the pyridine ring. Therefore, the compound (I) of the present invention can exist as both its acidic and basic salts. Examples of the acidic salt include salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid and the like, and salts with organic acids such as methanesulfonic acid, toluenesulfonic acid, oxalic acid, malonic acid, maleic acid, fumaric acid, succinic acid, tartaric acid, malic acid and the like. Examples of the basic salt include pharmacologically acceptable salts such as sodium salt, potassium salt, aluminium salt, magnesium salt, calcium salt and the like.
Specific examples of the compound (I) are as follows: ione; ne; dione; ne; dione; one; ne; and
The compound (I), the pharmacologically acceptable salt thereof, or the pure stereoisomeric form thereof has hypoglycemic and hypolipidemic activities. Further, the compound (I), the pharmacologically acceptable salt thereof or the pure stereoisomeric form thereof has low toxicity. For example, even when the compound obtained in Example 1 or 2 hereinafter was orally administered to mice in a dose of 300 mg/kg, no lethal case was observed. T

REFERENCES:
patent: 4444779 (1984-04-01), Kawamatsu et al.
patent: 4582839 (1986-04-01), Meguro
patent: 4687777 (1987-08-01), Meguro et al.
patent: 5183823 (1993-02-01), Sohda et al.
Sohda et al. CA113(3):23750k, 1990.
Meguro CA 104(21):186401a, 1985.
T. Sohda, et al., Chemical and Pharmaceutical Bulletin, "Studies on Antidiabetic Agents, II. Synthesis of 5-[4-(1-Methylcyclohexylmethoxy)-Benzyl]Thiazolidine-2,4-Dione (ADD-3878) and its Derivatives", pp. 3580-3600, vol. 30, No. 10, (Oct. 1982).

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Thiazolidinedione derivatives, production and use thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Thiazolidinedione derivatives, production and use thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Thiazolidinedione derivatives, production and use thereof will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-2181996

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.