Rational design and synthesis of novel 2,5-disubstituted cis- and trans-piperidine derivatives exhibiting differential activity for the dopamine transporter.
Herein, we report the rational design and synthesis of novel 2,5-disubstituted piperidine derivatives in the cis and trans isomeric forms. Out of these two isomers, the cis-isomer, 7a, was found to exhibit the most potent activity and selectivity for the dopamine transporter. These novel derivatives represent conformationally constrained version of piperidine analogue of GBR compounds.
Dutta
A K
AK
Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA. adutta@wizard.pharm.wayne.edu
Davis
M C
MC
Reith
M E
ME
D001559:Benzhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D015283:Citalopram / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
D001559:Benzhydryl Compounds; D002352:Carrier Proteins; D015283:Citalopram; D003042:Cocaine; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010880:Piperidines; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C442385:5-(4-fluorophenylmethylamino)-2-(diphenylmethyl)piperidine; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester