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

Eur J Med Chem. 2001 Jan;36(1):31-42. doi: 10.1016/s0223-5234(00)01191-0.

Abstract

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.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / drug effects*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Disease Models, Animal
  • Female
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Insulin / blood*
  • Male
  • Mice
  • Mice, Obese
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Structure-Activity Relationship
  • Thiazoles / pharmacology
  • Thiazolidinediones*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Oxadiazoles
  • Thiazoles
  • Thiazolidinediones
  • ciglitazone