A Novel Synthesis of 2-Arylpyrrolo[1,2- a]pyrimid-7-ones and Their Structure–Activity Relationships as Potent GnRH Receptor Antagonists

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 stuctures 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.