Substituted azaquinazolinones as modulators of GHSr-1a for the treatment of type II diabetes and obesity

Bioorg Med Chem Lett. 2012 Mar 15;22(6):2271-8. doi: 10.1016/j.bmcl.2012.01.078. Epub 2012 Feb 1.

Abstract

Substituted azaquinazolinones were identified as antagonists of the GHSr-1A receptor for the treatment of type II diabetes and obesity. Optimisation for potency and LogD lead to the identification of orally bioavailable, potent antagonists with improved selectivity over hERG.

MeSH terms

  • Administration, Oral
  • Animals
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / pharmacokinetics
  • Aza Compounds / pharmacology
  • Biological Availability
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Design
  • Ether-A-Go-Go Potassium Channels / metabolism
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology
  • Kinetics
  • Male
  • Obesity / drug therapy
  • Obesity / metabolism
  • Quinazolinones / chemical synthesis*
  • Quinazolinones / pharmacokinetics
  • Quinazolinones / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Ghrelin / antagonists & inhibitors*
  • Receptors, Ghrelin / metabolism
  • Structure-Activity Relationship

Substances

  • Aza Compounds
  • Ether-A-Go-Go Potassium Channels
  • Hypoglycemic Agents
  • Quinazolinones
  • Receptors, Ghrelin