title: Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor.
abstract: The current work discloses a novel cyclohexylarylamine chemotype with potent inhibition of the serotonin, norepinephrine, and dopamine transporters and potential for treatment of major depressive disorder. Optimized compounds 1 (SERT, NET, DAT, IC(50)=169, 85, 21 nM) and 42 (SERT, NET, DAT IC(50)=34, 295, 90 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 30 mpk po and were not general motor stimulants.
authors.affiliation: Discovery and Early Clinical Research, Sunovion Pharmaceuticals Inc., Marlborough, MA 01752, USA. liming.shao@sunovion.com
authors.forename: Liming
authors.initials: L
authors.lastname: Shao
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hewitt
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: John E
authors.initials: JE
authors.lastname: Campbell
authors.forename: Una C
authors.initials: UC
authors.lastname: Campbell
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Engel
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Spicer
authors.forename: Larry W
authors.initials: LW
authors.lastname: Hardy
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: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D018765:Dopamine Uptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D020128:Inhibitory Concentration 50; D008697:Methane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009638:Norepinephrine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000588:Amines; D000928:Antidepressive Agents; D018765:Dopamine Uptake Inhibitors; D012701:Serotonin; D008697:Methane; D009638:Norepinephrine