BMS-196085: a potent and selective full agonist of the human beta(3) adrenergic receptor.
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.
Gavai
A V
AV
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. ashvinikumar.gavai@bms.com
Sher
P M
PM
Mikkilineni
A B
AB
Poss
K M
KM
McCann
P J
PJ
Girotra
R N
RN
Fisher
L G
LG
Wu
G
G
Bednarz
M S
MS
Mathur
A
A
Wang
T C
TC
Sun
C Q
CQ
Slusarchyk
D A
DA
Skwish
S
S
Allen
G T
GT
Hillyer
D E
DE
Frohlich
B H
BH
Abboa-Offei
B E
BE
Cap
M
M
Waldron
T L
TL
George
R J
RJ
Tesfamariam
B
B
Harper
T W
TW
Ciosek
C P
CP
Young
D A
DA
Dickinson
K E
KE
Seymour
A A
AA
Arbeeny
C M
CM
Washburn
W N
WN
D000284:Administration, Oral; D000322:Adrenergic Agonists / Q000737:chemistry* / Q000494:pharmacology*; D058665:Adrenergic beta-1 Receptor Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D000813:Anilides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002522:Chlorocebus aethiops; D004353:Drug Evaluation, Preclinical; D005227:Fatty Acids / Q000097:blood; D006801:Humans; D051379:Mice; D008820:Mice, Obese; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D013329:Structure-Activity Relationship
D000322:Adrenergic Agonists; D058665:Adrenergic beta-1 Receptor Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D000813:Anilides; D001786:Blood Glucose; D005227:Fatty Acids; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3; C448380:BMS-196085