Isoxazolidine-3,5-dione and Noncyclic 1,3-Dicarbonyl Compounds as Hypoglycemic Agents

Isoxazolidine-3,5-dione and Noncyclic 1,3-Dicarbonyl Compounds as Hypoglycemic Agents

Isoxazolidine-3,5-dione 2 (JTT-501), one of the cyclic malonic acid derivatives, was found to decrease blood glucose at an oral dose of 38 mg/kg/day in KKAy mice and is currently undergoing evaluation in phase II clinical trials. Further studies on a series of malonic acids and related compounds sho...

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Bibliographic Details
Published in:Journal of medicinal chemistry Vol. 41; no. 11; pp. 1927 - 1933
Main Authors: Shinkai, Hisashi, Onogi, Syoji, Tanaka, Masahiro, Shibata, Tsutomu, Iwao, Megumi, Wakitani, Korekiyo, Uchida, Itsuo
Format: Journal Article
Language:English
Published: Washington, DC American Chemical Society 21-05-1998
Subjects:
3T3 Cells
Animals
Biological and medical sciences
Blood Glucose - metabolism
Cell Differentiation - drug effects
Drug Evaluation, Preclinical
General and cellular metabolism. Vitamins
Hypoglycemic Agents - chemical synthesis
Hypoglycemic Agents - pharmacology
Insulin - physiology
Isoxazoles - chemical synthesis
Isoxazoles - pharmacology
L Cells (Cell Line)
Male
Malonates - chemical synthesis
Malonates - pharmacology
Medical sciences
Mice
Oxazoles - chemical synthesis
Oxazoles - pharmacology
Pharmacology. Drug treatments
Triglycerides - metabolism
Endocrinopathy
Rodentia
Benzene derivatives
Oral administration
Non insulin dependent diabetes
In vitro
In vivo
Vertebrata
Chemotherapy
Hypoglycemic agent
Mammalia
Treatment
Structure activity relation
Mouse
Animal
Diester
Carboxamide
Chemical synthesis
Oxazole derivatives
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Summary:Isoxazolidine-3,5-dione 2 (JTT-501), one of the cyclic malonic acid derivatives, was found to decrease blood glucose at an oral dose of 38 mg/kg/day in KKAy mice and is currently undergoing evaluation in phase II clinical trials. Further studies on a series of malonic acids and related compounds showed that the 1,3-dicarbonyl structure was important for insulin-sensitizing activity. Dimethyl malonate 10, which was selected as a successor for 2, was the optimum compound in a series of 1,3-dicarbonyl compounds and was more potent than the corresponding thiazolidine-2,4-dione 1.
Bibliography:istex:0DD2E4B4128BE7326820598FA87113700CD956C6
ark:/67375/TPS-R19KR3XB-2
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-2623
1520-4804
DOI:10.1021/jm970771m