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

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

Affiliation

  • 1 Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543, USA. william.washburn@bms.com
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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