title: Identification of 1S,2R-milnacipran analogs as potent norepinephrine and serotonin transporter inhibitors.
abstract: A series of milnacipran analogs were synthesized and studied as monoamine transporter inhibitors, and several potent compounds with moderate lipophilicity were identified from the 1S,2R-isomers. Thus, 15l exhibited IC(50) values of 1.7nM at NET and 25nM at SERT, which were, respectively, 20- and 13-fold more potent than 1S,2R-milnacipran 1-II.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Bioscience, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
authors.forename: Junko
authors.initials: J
authors.lastname: Tamiya
authors.forename: Brian
authors.initials: B
authors.lastname: Dyck
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zhang
authors.forename: Kasey
authors.initials: K
authors.lastname: Phan
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fleck
authors.forename: Anna
authors.initials: A
authors.lastname: Aparicio
authors.forename: Florence
authors.initials: F
authors.lastname: Jovic
authors.forename: Joe A
authors.initials: JA
authors.lastname: Tran
authors.forename: Troy
authors.initials: T
authors.lastname: Vickers
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grey
authors.forename: Alan C
authors.initials: AC
authors.lastname: Foster
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D000078764:Milnacipran; D015394:Molecular Structure; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D003521:Cyclopropanes; D000078764:Milnacipran; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors