Discovery of novel aminothiadiazole amides as selective EP(3) receptor antagonists

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4292-5. doi: 10.1016/j.bmcl.2009.05.074. Epub 2009 May 27.

Abstract

This Letter discloses a series of 2-aminothiadiazole amides as selective EP(3) receptor antagonists. SAR optimization resulted in compounds with excellent functional activity in vitro. In addition, efforts to optimize DMPK properties in the rat are discussed. These efforts have resulted in the identification of potent, selective EP(3) receptor antagonists with excellent DMPK properties suitable for in vivo studies.

MeSH terms

  • Administration, Oral
  • Amides / chemistry*
  • Animals
  • Chemistry, Pharmaceutical / methods*
  • Dogs
  • Drug Design
  • Humans
  • Models, Chemical
  • Molecular Structure
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Prostaglandin E / antagonists & inhibitors*
  • Receptors, Prostaglandin E / chemistry*
  • Receptors, Prostaglandin E, EP3 Subtype
  • Structure-Activity Relationship
  • Thiadiazoles / chemistry*

Substances

  • Amides
  • PTGER3 protein, human
  • Ptger3 protein, rat
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP3 Subtype
  • Thiadiazoles