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

Authors
Chu, L Hutchins, JE Weber, AE Lo, JL Yang, YT Cheng, K Smith, RG Fisher, MH Wyvratt, MJ Goulet, MT
Citation
L. Chu et al., Initial structure-activity relationship of a novel class of nonpeptidyl GnRH receptor antagonists: 2-arylindoles, BIOORG MED, 11(4), 2001, pp. 509-513
Citations number
11
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
4
Year of publication
2001
Pages
509 - 513
Database
ISI
SICI code
0960-894X(20010226)11:4<509:ISROAN>2.0.ZU;2-S
Abstract
A nonpeptidyl GnRH receptor antagonist (1), with a unique 2-arylindole core , was identified through the Merck inhouse screening for binding affinity o n the rat GnRH receptor. SAR studies directed toward the alkoxy-ethanolamin e and 2-aryl groups resulted in a simpler lead structure with improved acti vity. This compound 50 exhibits a 60-fold improvement in binding activity o ver our initial lead 1. (C) 2001 Elsevier Science Ltd. All rights reserved.