title: Piperidine-based nocaine/modafinil hybrid ligands as highly potent monoamine transporter inhibitors: efficient drug discovery by rational lead hybridization.
abstract: Some piperidine-based nocaine/modafinil hybrid ligands have been designed, synthesized, and found to display an improved potency at all three monoamine transporters and particularly for DAT and/or NET. Some highly active and selective monoamine transporter inhibitors with low nanomolar to subnanomolar potency were identified. Ligands of this type may find important applications as positron emission tomography imaging tools and in the treatment of central nervous system disorders such as depression and sleep apnea.
authors.affiliation: Acenta Discovery, Inc., 9030 S. Rita Road, Suite 300, Tucson, Arizona 85747-9101, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Johnson
authors.forename: Yanping
authors.initials: Y
authors.lastname: Ye
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kozikowski
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D003042:Cocaine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D015195:Drug Design; D066298:In Vitro Techniques; D008024:Ligands; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D000077408:Modafinil; D009043:Motor Activity / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters / Q000037:antagonists & inhibitors*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D001559:Benzhydryl Compounds; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010880:Piperidines; D050486:Serotonin Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; C493216:Slc6a3 protein, rat; C493232:Slc6a4 protein, rat; D027981:Symporters; C466798:methyl 4-(4-chlorophenyl)-1-methylpiperidine-3-carboxylate; D003042:Cocaine; D000077408:Modafinil