Hypoglycemic Activity of a Series of α-Alkylthio and α-Alkoxy Carboxylic Acids Related to Ciglitazone

• Published in: Journal of medicinal chemistry Vol. 39; no. 20; pp. 3897 - 3907
• Main Authors: Hulin, Bernard, Newton, Linda S, Lewis, Diana M, Genereux, Paul E, Gibbs, E. Michael, Clark, David A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 27.09.1996; Amer Chemical Soc
• Subjects: 3T3 Cells; Adipocytes - drug effects; Animals; Benzofurans - chemistry; Benzofurans - pharmacology; Benzofurans - therapeutic use; Biological and medical sciences; Carboxylic Acids - chemistry; Chemistry, Medicinal; Diabetes Mellitus, Type 2 - drug therapy; General and cellular metabolism. Vitamins; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - therapeutic use; Life Sciences & Biomedicine; Medical sciences; Mice; Mice, Mutant Strains; Mice, Obese; Molecular Structure; Oxazoles - chemistry; Oxazoles - pharmacology; Oxazoles - therapeutic use; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Stereoisomerism; Structure-Activity Relationship; Thiazoles - chemistry; Thiazolidinediones; ANTIDIABETIC AGENTS; GLUCOSE; 3H-1,2,3,5-OXATHIADIAZOLE 2-OXIDES; OB/OB; ANTIHYPERGLYCEMIC ACTIVITY; COMPLICATIONS; MICE; DERIVATIVES; THIAZOLIDINE-2,4-DIONES; ADD-3878; Ether; Rodentia; Non insulin dependent diabetes; Organic sulfide; Vertebrata; Hypoglycemic agent; Mammalia; Structure activity relation; Mouse; Carboxylic acid; Animal; Stereospecificity; Benzofuran derivatives; Chemical synthesis; Oxazole derivatives; Enantiomer(-)
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm960230h

The thiazolidinedione moiety of ciglitazone and its analogues can be replaced by an α-alkoxy or α-thioether carboxylic acid group. The influence of the nature of the R group, the length of the connector to the aromatic backbone of the molecule, and the stereochemistry have been studied. The most potent compounds have glucose-lowering activity at doses as low as 0.01 mg/kg.