title: Synthesis and structure-activity relationships of selective norepinephrine reuptake inhibitors (sNRI) with a heterocyclic ring constraint.
abstract: The design, synthesis and SAR of a series of heterocyclic ring-constrained norepinephrine reuptake inhibitors are described. As racemates, the best compounds compare favorably with atomoxetine (IC(50)'s<10 nM) in potency at the transporter.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA. shudson@neurocrine.com
authors.forename: Sarah
authors.initials: S
authors.lastname: Hudson
authors.forename: Mehrak
authors.initials: M
authors.lastname: Kiankarimi
authors.forename: Wendy
authors.initials: W
authors.lastname: Eccles
authors.forename: Yalda S
authors.initials: YS
authors.lastname: Mostofi
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Genicot
authors.forename: Wesley
authors.initials: W
authors.lastname: Dwight
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fleck
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gogas
authors.forename: Warren S
authors.initials: WS
authors.lastname: Wade
mesh_terms: D000069445:Atomoxetine Hydrochloride; D002626:Chemistry, Pharmaceutical / Q000379:methods; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D015195:Drug Design; D006801:Humans; D007192:Indenes / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000201:enzymology; D008956:Models, Chemical; D009638:Norepinephrine / Q000737:chemistry / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D011437:Propylamines / Q000737:chemistry; D012701:Serotonin / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D007192:Indenes; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011437:Propylamines; C065434:MDL 27777; D012701:Serotonin; D000069445:Atomoxetine Hydrochloride; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009638:Norepinephrine