Discovery and structure-activity relationships of a novel class of quinazoline glucokinase activators

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5531-8. doi: 10.1016/j.bmcl.2009.08.064. Epub 2009 Aug 21.

Abstract

We describe design, syntheses and structure-activity relationships of a novel class of 4,6-disubstituted quinazoline glucokinase activators. Prototype quinazoline leads (4 and 5) were designed based on the X-ray analyses of the previous 2-aminobenzamide lead classes. Modifications of the quinazoline leads led to the identification of a potent GK activator (21d).

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Drug Discovery
  • Glucokinase / chemistry*
  • Glucokinase / metabolism
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacology
  • Mice
  • Quinazolines / chemical synthesis
  • Quinazolines / chemistry*
  • Quinazolines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Quinazolines
  • Glucokinase