1. Trishomocubane as a scaffold for the development of selective dopamine transporter (DAT) ligands.
- Author
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Banister SD, Moussa IA, Beinat C, Reynolds AJ, Schiavini P, Jorgensen WT, and Kassiou M
- Subjects
- Alkanes chemical synthesis, Alkanes pharmacology, Benzylamines chemical synthesis, Benzylamines pharmacology, Bridged-Ring Compounds chemical synthesis, Bridged-Ring Compounds pharmacology, Dopamine Plasma Membrane Transport Proteins metabolism, Dopamine Uptake Inhibitors chemical synthesis, Dopamine Uptake Inhibitors pharmacology, Ligands, Norepinephrine Plasma Membrane Transport Proteins antagonists & inhibitors, Norepinephrine Plasma Membrane Transport Proteins metabolism, Protein Binding, Receptors, sigma antagonists & inhibitors, Receptors, sigma metabolism, Serotonin Plasma Membrane Transport Proteins chemistry, Serotonin Plasma Membrane Transport Proteins metabolism, Structure-Activity Relationship, Alkanes chemistry, Benzylamines chemistry, Bridged-Ring Compounds chemistry, Dopamine Plasma Membrane Transport Proteins antagonists & inhibitors, Dopamine Uptake Inhibitors chemistry
- Abstract
In our continued exploration of trishomocubane derivatives with central nervous system (CNS) activity, N-arylalkyl-8-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecanes (10-13) displaying affinity for the sigma (σ) receptor were also found, in several cases, to interact with the dopamine transporter (DAT). Compound 12 was identified as the first trishomocubane-derived high affinity DAT ligand (K(i) = 1.2 nM), with greater than 8300-fold selectivity over the monoamine transporters NET and SERT, and only low to moderate affinity for σ(1) and σ(2) receptors., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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