title: Human beta3 adrenergic receptor agonists containing cyanoguanidine and nitroethylenediamine moieties.
abstract: Pyridineethanolamine derivatives containing cyanoguanidine or nitroethylenediamine moieties were examined as human beta3 adrenergic receptor (AR) agonists. Notably, indoline derivatives 6a and 11 were potent beta3 AR agonists (beta3 EC50 = 13 and 19 nM, respectively), which showed good selectivity over binding to and minimal activation of the beta1 and beta2 ARs.
authors.affiliation: Department of Medicinal Chemistry, Biochemistry and Physiology, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Brockunier
authors.forename: M R
authors.initials: MR
authors.lastname: Candelore
authors.forename: M A
authors.initials: MA
authors.lastname: Cascieri
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
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
authors.forename: E R
authors.initials: ER
authors.lastname: Parmee
mesh_terms: D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D003959:Diamines / Q000737:chemistry; D004980:Ethane / Q000031:analogs & derivatives / Q000737:chemistry; D006146:Guanidines / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D009595:Nitroparaffins / Q000737:chemistry; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D003959:Diamines; D006146:Guanidines; D009595:Nitroparaffins; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C014705:nitroethane; D000262:Adenylyl Cyclases; D004980:Ethane; C004711:dicyandiamido