A novel synthesis of 2-arylpyrrolo[1,2-a]pyrimid-7-ones and their structure-activity relationships as potent GnRH receptor antagonists

Bioorg Med Chem Lett. 2002 Feb 11;12(3):403-6. doi: 10.1016/s0960-894x(01)00780-6.

Abstract

In the process of developing GnRH receptor antagonists, a novel base-catalyzed cyclization of compounds 5a-b was discovered, which led to the formation of the 2-aryl pyrrolo[1,2-a]pyrimid-7-one core structures 6a-b. These intermediates were further modified at positions 1, 2, 4 and 6 to afford a series of potent GnRH antagonists with low nanomolar K(i) values.

MeSH terms

  • Animals
  • Humans
  • Indicators and Reagents
  • Kinetics
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / pharmacology*
  • Pyrroles / chemical synthesis*
  • Pyrroles / pharmacology*
  • Radioligand Assay
  • Rats
  • Receptors, LHRH / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Indicators and Reagents
  • Pyrimidinones
  • Pyrroles
  • Receptors, LHRH