Synthesis and structure-activity relationships of 1-arylmethyl-3-(2-aminopropyl)-5-aryl-6-methyluracils as potent GnRH receptor antagonists

Bioorg Med Chem Lett. 2003 Oct 6;13(19):3311-5. doi: 10.1016/s0960-894x(03)00620-6.

Abstract

The novel synthesis and SAR studies of 6-methyluracils as human GnRH receptor antagonists are discussed. Introduction of a small methyl substituent at the beta-position from N3 of the uracil improved the GnRH binding potency by 5- to 10-fold. The best compound from the series had binding affinity of 5 nM (K(i)) to the human GnRH receptor.

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Receptors, LHRH / antagonists & inhibitors*
  • Receptors, LHRH / physiology
  • Structure-Activity Relationship
  • Uracil / analogs & derivatives*
  • Uracil / chemical synthesis*
  • Uracil / pharmacology*

Substances

  • Receptors, LHRH
  • Uracil
  • 6-methyluracil