Derivatives of 1,4-bis(3-hydroxycarbonyl-4-hydroxyl)styrylbenzene as PTP1B inhibitors with hypoglycemic activity

Bioorg Med Chem. 2008 Sep 15;16(18):8643-52. doi: 10.1016/j.bmc.2008.07.090. Epub 2008 Aug 6.

Abstract

Disalicylic acid derivatives with stilbene and bis-styrylbenzene skeleton were synthesized as PTP1B inhibitors. The most potent in this series exhibited a submicromolar IC(50) value. One of the compounds 7b was tested in an animal model for its efficacy as an anti-diabetic or an anti-obesity agent. In feeding compound 7b to diet-induced obese mice, no significant differences in weight gain and food consumption were observed between the drug-treated and the obese control mice. However, 7b significantly lowered the fasting glucose level and improved the glucose tolerance in the obesity-induced diabetic mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Obesity Agents / chemical synthesis
  • Anti-Obesity Agents / pharmacology
  • Anti-Obesity Agents / therapeutic use*
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Disease Models, Animal
  • Fasting
  • Glucose Tolerance Test
  • Hyperglycemia / drug therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / drug therapy*
  • Salicylates / chemical synthesis
  • Salicylates / pharmacology
  • Salicylates / therapeutic use*
  • Stilbenes / chemical synthesis
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*
  • Structure-Activity Relationship
  • Styrenes / chemical synthesis
  • Styrenes / pharmacology
  • Styrenes / therapeutic use*
  • Weight Gain / drug effects*

Substances

  • Anti-Obesity Agents
  • Blood Glucose
  • Salicylates
  • Stilbenes
  • Styrenes
  • salicylsalicylic acid