title: Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors.
abstract: A series of milnacipran analogs containing a heteroaromatic group were synthesized and studied as monoamine transporter inhibitors. Many compounds exhibited higher potency than milnacipran at NET and NET/SERT with no significant change in lipophilicity. For example, compound R-26f was about 10-fold more potent than milnacipran with IC(50) values of 8.7 and 26nM at NET and SERT, respectively.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Bioscience, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
authors.forename: Troy
authors.initials: T
authors.lastname: Vickers
authors.forename: Brian
authors.initials: B
authors.lastname: Dyck
authors.forename: Junko
authors.initials: J
authors.lastname: Tamiya
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zhang
authors.forename: Florence
authors.initials: F
authors.lastname: Jovic
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grey
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fleck
authors.forename: Anna
authors.initials: A
authors.lastname: Aparicio
authors.forename: Michael
authors.initials: M
authors.lastname: Johns
authors.forename: Liping
authors.initials: L
authors.lastname: Jin
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.forename: Alan C
authors.initials: AC
authors.lastname: Foster
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D020650:Combinatorial Chemistry Techniques; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D000078764:Milnacipran; D015394:Molecular Structure; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D003521:Cyclopropanes; D000078764:Milnacipran; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors