title: Human beta3-adrenergic receptor agonists containing 1,2,3-triazole-substituted benzenesulfonamides.
abstract: Compounds containing a 1,2,3-triazole-substituted benzenesulfonamide were prepared and found to be potent and selective human beta3-adrenergic receptor agonists. The most interesting compound, trifluoromethylbenzyl analogue 12e (beta3 EC50 = 3.1 nM with >1500-fold selectivity over binding to both beta1- and beta2 receptors), stimulates lipolysis in the rhesus monkey (ED50 = 0.36 mg/kg) and is 25% orally bioavailable in the dog.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. linda_brockunier@merck.com
authors.forename: L L
authors.initials: LL
authors.lastname: Brockunier
authors.forename: E R
authors.initials: ER
authors.lastname: Parmee
authors.forename: H O
authors.initials: HO
authors.lastname: Ok
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: 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; D000818:Animals; D001682:Biological Availability; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007263:Infusions, Parenteral; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D008253:Macaca mulatta; D011485:Protein Binding; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D013610:Tachycardia / Q000139:chemically induced; D014230:Triazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D000096926:Benzenesulfonamides
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D000242:Cyclic AMP; D007545:Isoproterenol; D022702:Receptors, Adrenergic, beta-3; D013449:Sulfonamides; D014230:Triazoles; D000096926:Benzenesulfonamides