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

  • Bioorg Med Chem Lett. 2001 Dec 3;11(23):3035-9. doi: 10.1016/s0960-894x(01)00628-x.
W N Washburn  1 ,  P M Sher ,  K M Poss ,  R N Girotra ,  P J McCann ,  A V Gavai ,  A B Mikkilineni ,  A Mathur ,  P Cheng ,  T C Dejneka ,  C Q Sun ,  T C Wang ,  T W Harper ,  A D Russell ,  D A Slusarchyk ,  S Skwish ,  G T Allen ,  D E Hillyer ,  B H Frohlich ,  B E Abboa-Offei ,  M Cap ,  T L Waldron ,  R J George ,  B Tesfamariam ,  C P Ciosek Jr ,  D Ryono ,  D A Young ,  K E Dickinson ,  A A Seymour ,  C M Arbeeny ,  R E Gregg
Affiliations
  • 1. Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543, USA. [email protected]
PMID: 11714605 DOI: 10.1016/s0960-894x(01)00628-x
Abstract

Screening of the BMS collection identified 4-hydroxy-3-methylsulfonanilidoethanolamines as full beta 3 agonists. Substitution of the ethanolamine nitrogen with a benzyl group bearing a para hydrogen bond acceptor promoted beta(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-diarylmethylamines. This latter subset yielded a clinical candidate, BMS-194449 (35).(1)

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