Structure−Activity Relationship Studies of Highly Selective Inhibitors of the Dopamine Transporter: N-Benzylpiperidine Analogues of 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine
- 7 March 2003
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 46 (8) , 1465-1469
- https://doi.org/10.1021/jm020419v
Abstract
A series of 4-[2-[bis(4-fluorophenyl)methoxy]ethyl-1-benzylpiperidines were examined for their ability to bind to the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET). Binding results indicated that the presence of an electron-withdrawing group in the C4-position of the N-benzyl group is beneficial for binding to the DAT. Several analogues have been identified with high affinity for the DAT, up to 500-fold selectivity over the SERT and about 170-fold selectivity over the NET in binding and uptake inhibition assays.Keywords
This publication has 10 references indexed in Scilit:
- The dopamine uptake inhibitor GBR 12909: selectivity and molecular mechanism of actionPublished by Elsevier ,2002
- Piperidine Analogues of 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909): High Affinity Ligands for the Dopamine TransporterJournal of Medicinal Chemistry, 2002
- Expansion of Structure−Activity Studies of Piperidine Analogues of 1-[2-(Diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine (GBR 12935) Compounds by Altering Substitutions in the N-Benzyl Moiety and Behavioral Pharmacology of Selected MoleculesJournal of Medicinal Chemistry, 2001
- Structure−Activity Relationship Studies of 4-[2-(Diphenylmethoxy)ethyl]-1-benzylpiperidine Derivatives and Their N-Analogues: Evaluation of Behavioral Activity of O- and N-Analogues and Their Binding to Monoamine TransportersJournal of Medicinal Chemistry, 2001
- Highly Selective, Novel Analogs of 4-[2-(Diphenylmethoxy)ethyl]- 1-benzylpiperidine for the Dopamine Transporter: Effect of Different Aromatic Substitutions on Their Affinity and SelectivityJournal of Medicinal Chemistry, 1997
- Sustained Decrease in Cocaine-Maintained Responding in Rhesus Monkeys with 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]- 4-(3-hydroxy-3-phenylpropyl)piperazinyl Decanoate, a Long-Acting Ester Derivative of GBR 12909Journal of Medicinal Chemistry, 1996
- Identification of a GBR12935 homolog, LR1111, which is over 4,000‐fold selective for the dopamine transporter, relative to serotonin and norepinephrine transportersSynapse, 1993
- Cocaine and GBR12909 produce equivalent motoric responses at different occupancy of the dopamine transporterPharmacology Biochemistry and Behavior, 1992
- GBR12909 antagonizes the ability of cocaine to elevate extracellular levels of dopaminePharmacology Biochemistry and Behavior, 1991
- Tight binding dopamine reuptake inhibitors as cocaine antagonistsFEBS Letters, 1989