Novel Benzoxazole 2, 4-Thiazolidinediones as Potent Hypoglycemic Agents. Synthesis and Structure-Activity Relationships

Abstract

A new series of benzoxazole 2, 4-thiazolidinediones was synthesized and evaluated for hypoglycemic activity in genetically obese and diabetic yellow KK mice. 2-Arymethyl- and 2-(heteroarhylmethyl)benzoxazole derivatives showed far more potent activity than known 2, 4-thiazolidinedione derivatives such as ciglitazone, troglitazone and pioglitazone. A facile synthesis of benzoxazole 2, 4-thiazolidinediones was also established using aminophenol 2, 4-thiazolidinedione (11) as a key intermediate. Details of synthesis and structure-activity relationships for this series are described.