title: Human beta3 adrenergic receptor agonists containing cyclic ureidobenzenesulfonamides.
abstract: Human beta3 adrenergic receptor agonists containing 5-membered ring ureas were shown to be potent partial agonists with excellent selectivity over beta1 and beta2 binding. L-760,087 (4a) and L-764,646 (5a) (beta3 EC50 = 18 and 14 nM, respectively) stimulate lipolysis in rhesus monkeys (ED50 = 0.2 and 0.1 mg/kg, respectively) with minimal effects on heart rate. Oral absorption in dogs is improved over other urea analogs.
authors: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors: E R
authors: ER
authors: Parmee
authors: E M
authors: EM
authors: Naylor
authors: L
authors: L
authors: Perkins
authors: V J
authors: VJ
authors: Colandrea
authors: H O
authors: HO
authors: Ok
authors: M R
authors: MR
authors: Candelore
authors: M A
authors: MA
authors: Cascieri
authors: L
authors: L
authors: Deng
authors: W P
authors: WP
authors: Feeney
authors: M J
authors: MJ
authors: Forrest
authors: G J
authors: GJ
authors: Hom
authors: D E
authors: DE
authors: MacIntyre
authors: R R
authors: RR
authors: Miller
authors: R A
authors: RA
authors: Stearns
authors: C D
authors: CD
authors: Strader
authors: L
authors: L
authors: Tota
authors: M J
authors: MJ
authors: Wyvratt
authors: M H
authors: MH
authors: Fisher
authors: A E
authors: AE
authors: Weber
mesh_terms: D000284:Administration, Oral; 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; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008253:Macaca mulatta; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; C112650:L 755507; C119124:L 757793; C119126:L 760087; C119125:L 764646; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D013449:Sulfonamides; D014508:Urea