Initial structure–activity relationship of a novel class of nonpeptidyl GnRH receptor antagonists: 2-arylindoles

L Chu, JE Hutchins, AE Weber, JL Lo, YT Yang…

Index: Chu, Lin; Hutchins, Jennifer E.; Weber, Ann E.; Lo, Jane-Ling; Yang, Yi-Tien; Cheng, Kang; Smith, Roy G.; Fisher, Michael H.; Wyvratt, Matthew J.; Goulet, Mark T. Bioorganic and Medicinal Chemistry Letters, 2001 , vol. 11, # 4 p. 509 - 513

Full Text: HTML

Citation Number: 50

Abstract

A nonpeptidyl GnRH receptor antagonist (1), with a unique 2-arylindole core, was identified through the Merck in-house screening for binding affinity on the rat GnRH receptor. SAR studies directed toward the alkoxy-ethanolamine and 2-aryl groups resulted in a simpler lead structure with improved activity. This compound 50 exhibits a 60-fold improvement in binding activity over our initial lead 1.