title: Structure-activity relationships of the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ol series of monoamine reuptake inhibitors.
abstract: The SAR of a series of 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols as monoamine reuptake inhibitors, with a goal to improve both potency toward inhibiting the norepinephrine transporter and selectivity over the serotonin transporter, is reported. The effect of specific substitution on both the 3-phenyl group and the indole moiety were explored. This study led to the discovery of compound 20 which inhibited the norepinephrine transporter with an IC50 value of 4 nM while exhibiting 86-fold selectivity over the serotonin transporter.
authors.affiliation: Chemical Sciences, Wyeth Research, Collegeville, PA 19426, United States. paige.mahaney@boehringeringelheim.com
authors.forename: Paige E
authors.initials: PE
authors.lastname: Mahaney
authors.forename: Callain Y
authors.initials: CY
authors.lastname: Kim
authors.forename: Richard D
authors.initials: RD
authors.lastname: Coghlan
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Cohn
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Heffernan
authors.forename: Christine A
authors.initials: CA
authors.lastname: Huselton
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Terefenko
authors.forename: An T
authors.initials: AT
authors.lastname: Vu
authors.forename: Puwen
authors.initials: P
authors.lastname: Zhang
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Burroughs
authors.forename: Scott A
authors.initials: SA
authors.lastname: Cosmi
authors.forename: Jenifer A
authors.initials: JA
authors.lastname: Bray
authors.forename: Grace H
authors.initials: GH
authors.lastname: Johnston
authors.forename: Darlene C
authors.initials: DC
authors.lastname: Deecher
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Trybulski
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D023421:Models, Animal; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D018759:Adrenergic Uptake Inhibitors; D007211:Indoles; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors