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

• Published in: Bioorganic & medicinal chemistry letters Vol. 11; no. 23; pp. 3041 - 3044
• Main Authors: Gavai, A V, Sher, P M, Mikkilineni, A B, Poss, K M, McCann, P J, Girotra, R N, Fisher, L G, Wu, G, Bednarz, M S, Mathur, A, Wang, T C, Sun, C Q, Slusarchyk, D A, Skwish, S, Allen, G T, Hillyer, D E, Frohlich, B H, Abboa-Offei, B E, Cap, M, Waldron, T L, George, R J, Tesfamariam, B, Harper, T W, Ciosek, Jr, C P, Young, D A, Dickinson, K E, Seymour, A A, Arbeeny, C M, Washburn, W N
• Format: Journal Article
• Language: English
• Published: England 03.12.2001
• Subjects: 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; Cercopithecus aethiops; Drug Evaluation, Preclinical; Fatty Acids - blood; Humans; Mice; Mice, Obese; Receptors, Adrenergic, beta-1 - metabolism; Receptors, Adrenergic, beta-3 - metabolism; Structure-Activity Relationship
• ISSN: 0960-894X
• DOI: 10.1016/S0960-894X(01)00629-1

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.