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 as 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 the prepared methoxy- and ethoxy-linked oxazole 1,2,4-oxadiazolidine-3,5-dion...

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Veröffentlicht in:European journal of medicinal chemistry 2001, Vol.36 (1), p.31-42
Hauptverfasser: Malamas, Michael S, Sredy, Janet, McCaleb, Michael, Gunawan, Iwan, Mihan, Brenda, Sullivan, Donald
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Sprache:eng
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Zusammenfassung:A series of 1,2,4-oxadiazolidine-3,5-diones was synthesized and evaluated as 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 the prepared methoxy- and ethoxy-linked oxazole 1,2,4-oxadiazolidine-3,5-diones normalized plasma glucose levels at the 100 mg kg −1 oral dose in the db/db diabetic mouse model, and several amongst them reduced the glucose levels at the 20 mg kg −1 oral dose. The most potent compounds in the db/db mouse 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 plasma 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 diabetic mouse models normalizing plasma glucose levels at the 100 mg kg −1 oral dose.
ISSN:0223-5234
1768-3254
DOI:10.1016/S0223-5234(00)01191-0