Identification of 1-arylmethyl-3- (2-aminoethyl)-5-aryluracil as novel gonadotropin-releasing hormone receptor antagonists

J Med Chem. 2003 May 22;46(11):2023-6. doi: 10.1021/jm034041s.

Abstract

Based on SAR from bicyclic GnRH antagonists such as 6-aminomethyl-7-arylpyrrolo[1,2-a]pyrimid-4-ones (1) and 2-aryl-3-aminomethylimidazolo[1,2-a]pyrimid-5-ones (2a,b), a series of novel uracil compounds (4) were derived as the GnRH antagonists. Their syntheses and initial SAR are discussed herein. This is the first time that monocycle-based GnRH receptor antagonists are reported.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Drug Stability
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Metabolic Clearance Rate
  • Mice
  • Microsomes, Liver / metabolism
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Receptors, LHRH / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Uracil / chemical synthesis*
  • Uracil / chemistry
  • Uracil / pharmacology

Substances

  • Imidazoles
  • Pyrroles
  • Receptors, LHRH
  • Uracil