title: Discovery of N-methyl-1-(1-phenylcyclohexyl)ethanamine, a novel triple serotonin, norepinephrine and dopamine reuptake inhibitor.
abstract: Novel chiral cyclohexylaryl amines were developed with potent reuptake inhibition against the serotonin, norepinephrine and dopamine transporters and activity at 10 and 30 mpk PO in the mouse tail suspension test. Prototype compound 31 (SERT, NET, DAT IC(50) ≤ 1, 21, 28 nM) was highly brain penetrant, had minimal CYP and hERG inhibition, and represents a previously undisclosed architecture with potential for treatment of major depressive disorder.
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; D003500:Cyclization; D018765:Dopamine Uptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D009638:Norepinephrine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012701:Serotonin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000588:Amines; D018765:Dopamine Uptake Inhibitors; D012701:Serotonin; D009638:Norepinephrine