Human beta3 adrenergic receptor agonists containing imidazolidinone and imidazolone benzenesulfonamides.
The cyclopentylpropylimidazolidinone L-766,892 is a potent beta3 AR agonist (EC50 5.7 nM, 64% activation) with 420- and 130-fold selectivity over binding to the beta1 and beta2 ARs, respectively. In anesthetized rhesus monkeys, L-766,892 elicited dose-dependent hyperglycerolemia (ED50 0.1 mg/kg) with minimal effects on heart rate.
Naylor
E M
EM
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Parmee
E R
ER
Colandrea
V J
VJ
Perkins
L
L
Brockunier
L
L
Candelore
M R
MR
Cascieri
M A
MA
Colwell
L F
LF
Deng
L
L
Feeney
W P
WP
Forrest
M J
MJ
Hom
G J
GJ
MacIntyre
D E
DE
Strader
C D
CD
Tota
L
L
Wang
P R
PR
Wyvratt
M J
MJ
Fisher
M H
MH
Weber
A E
AE
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008253:Macaca mulatta; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3; D013329:Structure-Activity Relationship
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D003517:Cyclopentanes; D007093:Imidazoles; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C119127:cyclopentylpropylimidazolidinone