- Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor
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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, IC50 = 169, 85, 21 nM) and 42 (SERT, NET, DAT IC50 = 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.
- Shao, Liming,Hewitt, Michael C.,Wang, Fengjiang,Malcolm, Scott C.,Ma, Jianguo,Campbell, John E.,Campbell, Una C.,Engel, Sharon R.,Spicer, Nancy A.,Hardy, Larry W.,Schreiber, Rudy,Spear, Kerry L.,Varney, Mark A.
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p. 1438 - 1441
(2011/04/16)
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- Arylcyclobutylalkylamines and anti-depression composition and methods using same
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Compounds of formula I STR1 in which R1 is H or C1-3 alkyl; R2 is H or C1-3 alkyl; R3 and/or R4 are H, C1-3 alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-7 cycloalkyl or R3 and R4 together with the nitrogen atom form a heterocyclic ring system; R5 and/or R6 are H, halo, CF3, or C1-3 alkyl (with the proviso that R5 and R6 cannot both be H or methyl) or R5 and R6 together with the carbon atoms to which they are attached form a second benzene ring and R7 and/or R8 are H or C1-3 alkyl show therapeutic activity in the treatment of depression. Pharmaceutical compositions and processes for preparing compounds of formula I are disclosed.
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