title: 3-Pyridyloxypropanolamine agonists of the beta 3 adrenergic receptor with improved pharmacokinetic properties.
abstract: Pyridyloxypropanolamines L-749,372 (8, beta 3 EC50 = 3.6 nM) and L-750,355 (29, beta 3 EC50 = 13 nM) are selective partial agonists of the human receptor, with 33% and 49% activation, respectively. Both stimulate lipolysis in rhesus monkeys (ED50 = 2 and 0.8 mg/kg, respectively), with minimal effects on heart rate. Oral bioavailability in dogs, 41% for L-749,372 and 47% for L-750,355, is improved relative to phenol analogs.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Weber
authors.forename: H O
authors.initials: HO
authors.lastname: Ok
authors.forename: R F
authors.initials: RF
authors.lastname: Alvaro
authors.forename: M R
authors.initials: MR
authors.lastname: Candelore
authors.forename: M A
authors.initials: MA
authors.lastname: Cascieri
authors.forename: S H
authors.initials: SH
authors.lastname: Chiu
authors.forename: L
authors.initials: L
authors.lastname: Deng
authors.forename: M J
authors.initials: MJ
authors.lastname: Forrest
authors.forename: G J
authors.initials: GJ
authors.lastname: Hom
authors.forename: J E
authors.initials: JE
authors.lastname: Hutchins
authors.forename: J
authors.initials: J
authors.lastname: Kao
authors.forename: D E
authors.initials: DE
authors.lastname: MacIntyre
authors.forename: R J
authors.initials: RJ
authors.lastname: Mathvink
authors.forename: D
authors.initials: D
authors.lastname: McLoughlin
authors.forename: R R
authors.initials: RR
authors.lastname: Miller
authors.forename: R C
authors.initials: RC
authors.lastname: Newbold
authors.forename: T V
authors.initials: TV
authors.lastname: Olah
authors.forename: E R
authors.initials: ER
authors.lastname: Parmee
authors.forename: L
authors.initials: L
authors.lastname: Perkins
authors.forename: R A
authors.initials: RA
authors.lastname: Stearns
authors.forename: C D
authors.initials: CD
authors.lastname: Strader
authors.forename: J
authors.initials: J
authors.lastname: Szumiloski
authors.forename: Y S
authors.initials: YS
authors.lastname: Tang
authors.forename: L
authors.initials: L
authors.lastname: Tota
authors.forename: M H
authors.initials: MH
authors.lastname: Fisher
mesh_terms: D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001667:Binding, Competitive; D001682:Biological Availability; D004285:Dogs; D006801:Humans; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects; D008253:Macaca mulatta; D015394:Molecular Structure; D011412:Propanolamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D011725:Pyridines; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011725:Pyridines; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D013449:Sulfonamides