Novel benzoxazole 2,4-thiazolidinediones as potent hypoglycemic agents. Synthesis and structure-activity relationships.

A new series of benzoxazole 2,4-thiazolidinediones was synthesized and evaluated for hypoglycemic activity in genetically obese and diabetic yellow KK mice. 2-Arylmethyl- and 2-(heteroarylmethyl)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.