L-770,644: a potent and selective human beta3 adrenergic receptor agonist with improved oral bioavailability.
L-770,644 (9c) is a potent and selective agonist of the human beta3 adrenergic receptor (EC50 = 13 nM). It shows good oral bioavailability in both dogs and rats (%F = 27), and is a full agonist for glycerolemia in the rhesus monkey (ED50 = 0.21 mg/kg). Based on its desirable in vitro and in vivo properties, L-770,644 was chosen for further preclinical evaluation.
Shih
T L
TL
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Candelore
M R
MR
Cascieri
M A
MA
Chiu
S H
SH
Colwell
L F
LF
Deng
L
L
Feeney
W P
WP
Forrest
M J
MJ
Hom
G J
GJ
MacIntyre
D E
DE
Miller
R R
RR
Stearns
R A
RA
Strader
C D
CD
Tota
L
L
Wyvratt
M J
MJ
Fisher
M H
MH
Weber
A E
AE
D000284:Administration, Oral; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051381:Rats; D013449:Sulfonamides / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000494:pharmacology*; D013777:Tetrazoles / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D013449:Sulfonamides; D013777:Tetrazoles; C120629:L 770644