Antihyperglycemic activity of new 1,2,4-oxadiazolidine-3,5-diones

A series of 1,2,4-oxadiazolidine-3,5-diones was synthesized and evaluated a s oral antihyperglycemic agents in the obese insulin resistant db/db and ob /ob mouse - the two models for Type 2 diabetes mellitus. The majority of th e prepared methoxy- and ethoxy-linked oxazole 1,2,4-oxadiazolidine-3,5-dion es normalized plasma glucose levels at the 100 mg kg(-1) oral dose in the d b/db diabetic mouse model, and several amongst them reduced the glucose lev els at the 20 mg kg(-1) oral dose. The most potent compounds in the db/db m ouse model were also active in the ob/ob mouse model normalizing the plasma glucose levels at the 20 mg kg(-1) oral dose. The trifluoromethoxy analog 32 was the most active compound of the series, reducing significantly the p lasma glucose levels at the 5 mg kg(-1) oral dose. Oxadiazole-tailed 1,2,4- oxadiazolidine-3,5-diones were also active in both the db/db and ob/ob diab etic mouse models normalizing plasma glucose levels at the 100 mg kg(-1) or al dose. (C) 2001 Editions scientifiques et medicales Elsevier SAS.