Discovery of an orally bioavailable alkyl oxadiazole beta3 adrenergic receptor agonist.
5-n-Pentyl oxadiazole substituted benzenesulfonamide 8 is a potent and selective beta3 adrenergic receptor agonist (beta3 EC50 = 23 nM, beta1 IC50 = 3000 nM, beta2 IC50 = 3000 nM). The compound has high oral bioavailability in dogs (62%) and rats (36%) and is among the most orally bioavailable beta3 adrenergic receptor agonists reported to date.
Feng
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DD
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway NJ 07065, USA. danqing_feng@merck.com
Biftu
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T
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
Miller
R R
RR
Stearns
R A
RA
Strader
C D
CD
Tota
L
L
Wyvratt
M J
MJ
Fisher
M H
MH
Weber
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D000284:Administration, Oral; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D016466:CHO Cells; D006224:Cricetinae; D004285:Dogs; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010069:Oxadiazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D010069:Oxadiazoles