Beta 3 agonists. Part 1: Evolution from inception to BMS-194449

Authors
Washburn, WN Sher, PM Poss, KM Girotra, RN McCann, PJ Gavai, AV Mikkilineni, AB Mathur, A Cheng, P Dejneka, TC Sun, CQ Wang, TC Harper, TW Russell, AD Slusarchyk, DA Skwish, S Allen, GT Hillyer, DE Frohlich, BH Abboa-Offei, BE Cap, M Waldron, TL George, RJ Tesfamariam, B Ciosek, CP Ryono, D Young, DA Dickinson, KE Seymour, AA Arbeeny, CM Gregg, RE
Citation
Wn. Washburn et al., Beta 3 agonists. Part 1: Evolution from inception to BMS-194449, BIOORG MED, 11(23), 2001, pp. 3035-3039
Citations number
20
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
23
Year of publication
2001
Pages
3035 - 3039
Database
ISI
SICI code
0960-894X(200112)11:23<3035:B3AP1E>2.0.ZU;2-D
Abstract
Screening of the BMS collection identified 4-hydroxy-3-methylsulfonanilidoe thanolamines as full beta 3 agonists. Substitution of the ethanolamine nitr ogen with a benzyl group bearing a para hydrogen bond acceptor promoted bet a (3) selectivity. SAR elucidation established that highly selective beta ( 3) agonists were generated upon substitution of C-alpha with either benzyl to form (R)-1,2-diarylethylamines or with aryl to generate 1,1-diarylmethyl amines. This latter subset yielded a clinical candidate, BMS-194449 (35).(1 ) (C) 2001 Elsevier Science Ltd. All rights reserved.