BMS-196085: a potent and selective full agonist of the human beta(3) adrenergic receptor

A V Gavai; P M Sher; A B Mikkilineni; K M Poss; P J McCann; R N Girotra; L G Fisher; G Wu; M S Bednarz; A Mathur; T C Wang; C Q Sun; 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; T W Harper; C P Ciosek Jr; D A Young; K E Dickinson; A A Seymour; C M Arbeeny; W N Washburn

doi:10.1016/s0960-894x(01)00629-1

BMS-196085: a potent and selective full agonist of the human beta(3) adrenergic receptor

Bioorg Med Chem Lett. 2001 Dec 3;11(23):3041-4. doi: 10.1016/s0960-894x(01)00629-1.

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. [email protected]

PMID: 11714606
DOI: 10.1016/s0960-894x(01)00629-1

Abstract

A series of 4-hydroxy-3-methylsulfonanilido-1,2-diarylethylamines were prepared and evaluated for their human beta(3) adrenergic receptor agonist activity. SAR studies led to the identification of BMS-196085 (25), a potent beta(3) full agonist (K(i)=21 nM, 95% activation) with partial agonist (45%) activity at the beta(1) receptor. Based on its desirable in vitro and in vivo properties, BMS-196085 was chosen for clinical evaluation.

MeSH terms

Administration, Oral
Adrenergic Agonists / chemistry*
Adrenergic Agonists / pharmacology*
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-3 Receptor Agonists*
Anilides / chemistry*
Anilides / pharmacology*
Animals
Blood Glucose / metabolism
Chlorocebus aethiops
Drug Evaluation, Preclinical
Fatty Acids / blood
Humans
Mice
Mice, Obese
Receptors, Adrenergic, beta-1 / metabolism
Receptors, Adrenergic, beta-3 / metabolism
Structure-Activity Relationship

Substances

Adrenergic Agonists
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-3 Receptor Agonists
Anilides
Blood Glucose
Fatty Acids
Receptors, Adrenergic, beta-1
Receptors, Adrenergic, beta-3
BMS-196085