Discovery of novel 3,6-disubstituted 2-pyridinecarboxamide derivatives as GK activators

Bioorg Med Chem Lett. 2009 May 15;19(10):2718-21. doi: 10.1016/j.bmcl.2009.03.137. Epub 2009 Mar 29.

Abstract

A novel class of 3,6-disubstituted 2-pyridinecarboxamide derivatives was designed based on X-ray analysis of the 2-aminobenzamide lead class. Subsequent chemical modification led to the discovery of potent GK activators which eliminate potential toxicity concerns associated with an aniline group of the lead structure. Compound 7 demonstrated glucose lowering effect in a rat OGTT model.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacokinetics
  • Animals
  • Crystallography, X-Ray
  • Disease Models, Animal
  • Drug Discovery
  • Glucokinase / chemistry
  • Glucokinase / metabolism*
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacokinetics
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacokinetics
  • Rats
  • Structure-Activity Relationship

Substances

  • Amides
  • Hypoglycemic Agents
  • Pyridines
  • Glucokinase