title: Beta 3 agonists. Part 1: evolution from inception to BMS-194449.
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)
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543, USA. william.washburn@bms.com
authors.forename: W N
authors.initials: WN
authors.lastname: Washburn
authors.forename: P M
authors.initials: PM
authors.lastname: Sher
authors.forename: K M
authors.initials: KM
authors.lastname: Poss
authors.forename: R N
authors.initials: RN
authors.lastname: Girotra
authors.forename: P J
authors.initials: PJ
authors.lastname: McCann
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authors.lastname: Mikkilineni
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authors.lastname: Mathur
authors.forename: P
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authors.lastname: Cheng
authors.forename: T C
authors.initials: TC
authors.lastname: Dejneka
authors.forename: C Q
authors.initials: CQ
authors.lastname: Sun
authors.forename: T C
authors.initials: TC
authors.lastname: Wang
authors.forename: T W
authors.initials: TW
authors.lastname: Harper
authors.forename: A D
authors.initials: AD
authors.lastname: Russell
authors.forename: D A
authors.initials: DA
authors.lastname: Slusarchyk
authors.forename: S
authors.initials: S
authors.lastname: Skwish
authors.forename: G T
authors.initials: GT
authors.lastname: Allen
authors.forename: D E
authors.initials: DE
authors.lastname: Hillyer
authors.forename: B H
authors.initials: BH
authors.lastname: Frohlich
authors.forename: B E
authors.initials: BE
authors.lastname: Abboa-Offei
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authors.lastname: Cap
authors.forename: T L
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authors.lastname: Waldron
authors.forename: R J
authors.initials: RJ
authors.lastname: George
authors.forename: B
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authors.lastname: Tesfamariam
authors.forename: C P
authors.initials: CP
authors.lastname: Ciosek
authors.forename: D
authors.initials: D
authors.lastname: Ryono
authors.forename: D A
authors.initials: DA
authors.lastname: Young
authors.forename: K E
authors.initials: KE
authors.lastname: Dickinson
authors.forename: A A
authors.initials: AA
authors.lastname: Seymour
authors.forename: C M
authors.initials: CM
authors.lastname: Arbeeny
authors.forename: R E
authors.initials: RE
authors.lastname: Gregg
mesh_terms: D000284:Administration, Oral; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000737:chemistry* / Q000494:pharmacology*; D000813:Anilides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D002522:Chlorocebus aethiops; D004353:Drug Evaluation, Preclinical; D019856:Ethanolamine / Q000737:chemistry* / Q000494:pharmacology*; D004983:Ethanolamines; D006801:Humans; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000813:Anilides; D004983:Ethanolamines; D019856:Ethanolamine; C448379:BMS-194449