title: Discovery of an orally bioavailable alkyl oxadiazole beta3 adrenergic receptor agonist.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway NJ 07065, USA. danqing_feng@merck.com
authors.forename: D D
authors.initials: DD
authors.lastname: Feng
authors.forename: T
authors.initials: T
authors.lastname: Biftu
authors.forename: M R
authors.initials: MR
authors.lastname: Candelore
authors.forename: M A
authors.initials: MA
authors.lastname: Cascieri
authors.forename: L F
authors.initials: LF
authors.lastname: Colwell
authors.forename: L
authors.initials: L
authors.lastname: Deng
authors.forename: W P
authors.initials: WP
authors.lastname: Feeney
authors.forename: M J
authors.initials: MJ
authors.lastname: Forrest
authors.forename: G J
authors.initials: GJ
authors.lastname: Hom
authors.forename: D E
authors.initials: DE
authors.lastname: MacIntyre
authors.forename: R R
authors.initials: RR
authors.lastname: Miller
authors.forename: R A
authors.initials: RA
authors.lastname: Stearns
authors.forename: C D
authors.initials: CD
authors.lastname: Strader
authors.forename: L
authors.initials: L
authors.lastname: Tota
authors.forename: M J
authors.initials: MJ
authors.lastname: Wyvratt
authors.forename: M H
authors.initials: MH
authors.lastname: Fisher
authors.forename: A E
authors.initials: AE
authors.lastname: Weber
mesh_terms: 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
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D010069:Oxadiazoles