Thiophene derivatives: a new series of potent norepinephrine and serotonin reuptake inhibitors.
A series of (1S,3S,6R,10S)-(Z)-9-(thienylmethylene- or substituted thienylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes was prepared and evaluated for the ability to block dopamine, serotonin, and norepinephrine reuptake by their respective transporters. Compound 5b is a NET-selective inhibitor, 5c is a mixed NET- and SERT-selective inhibitor, while 11 is a SERT-selective inhibitor.
Zhang
Ao
A
Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20007-2197, USA.
Zhou
Guochun
G
Rong
Suo-Bao
SB
Johnson
Kenneth M
KM
Zhang
Mei
M
Kozikowski
Alan P
AP
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008968:Molecular Conformation; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D051381:Rats; D012701:Serotonin / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D027981:Symporters / Q000378:metabolism; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D027981:Symporters; D013876:Thiophenes; C493226:Slc6a2 protein, rat; C493232:Slc6a4 protein, rat