title: Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors.
abstract: The present work describes a series of novel chiral amines that potently inhibit the in vitro reuptake of serotonin, norepinephrine and dopamine (triple reuptake inhibitors) and were active in vivo in a mouse model predictive of antidepressant like activity. The detailed synthesis and in vitro activity and ADME profile of compounds is described, which represent a previously undisclosed triple reuptake inhibitor chemotype.
authors.affiliation: Discovery and Early Clinical Research, Sepracor Inc., 84 Waterford Drive, Marlborough, MA 01752, USA. liming.shao@sepracor.com
authors.forename: Liming
authors.initials: L
authors.lastname: Shao
authors.forename: Fengjiang
authors.initials: F
authors.lastname: Wang
authors.forename: Scott C
authors.initials: SC
authors.lastname: Malcolm
authors.forename: Jianguo
authors.initials: J
authors.lastname: Ma
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hewitt
authors.forename: Una C
authors.initials: UC
authors.lastname: Campbell
authors.forename: Larry R
authors.initials: LR
authors.lastname: Bush
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Spicer
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Engel
authors.forename: Lakshmi D
authors.initials: LD
authors.lastname: Saraswat
authors.forename: Larry W
authors.initials: LW
authors.lastname: Hardy
authors.forename: Patrick
authors.initials: P
authors.lastname: Koch
authors.forename: Rudy
authors.initials: R
authors.lastname: Schreiber
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Spear
authors.forename: Mark A
authors.initials: MA
authors.lastname: Varney
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D051379:Mice; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D014179:Neurotransmitter Uptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D009281:Naphthalenes; D014179:Neurotransmitter Uptake Inhibitors; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine