Synthesis and Dopamine Transporter Affinity of 2-(Methoxycarbonyl)-9-methyl-3-phenyl-9-azabicyclo[3.3.1]nonane Derivatives

Citations Over Time

Abstract

A series of 9-methyl-3 beta-phenyl-2-substituted-9-azabicyclo[3.3.1]nonane derivatives were synthesized and evaluated as cocaine-binding site ligands at the dopamine transporter (DAT). The conformation of the bicyclic structures and the stereochemistry of the substituents were determined by NMR and X-ray crystallography. The in vitro binding affinity (Ki) of the 9-azabicyclo[3.3.1]nonane derivatives was measured in rat caudate-putamen tissue, and they were found to be 100-fold (Ki = 2-14 microM) less potent than cocaine and other tropane analogs. From these results it is evident that the cocaine-binding site at the DAT is very sensitive to structural modifications of the unsubstituted methylene bridge [C(6)-C(7)] of cocaine and cocaine-like compounds.

Related Papers

• → Evidence for mutually exclusive binding of cocaine, BTCP, GBR 12935, and dopamine to the dopamine transporter(1992)78 cited
• → 2-Carbomethoxy-3-(diarylmethoxy)-1αH,5αH-tropane Analogs: Synthesis and Inhibition of Binding at the Dopamine Transporter and Comparison with Piperazines of the GBR Series(1996)48 cited
• → Species differences in functions of dopamine transporter: paucity of MPP+ uptake and cocaine binding in bovine dopamine transporter(1996)18 cited
• → Structural significance of azaheterocyclic amines related to Parkinson's disease for dopamine transporter(1998)31 cited
• → Development of Peptidic Dopamine Transporter Inhibitors via Aromatic Modification-Mediated Conformational Restriction(2006)7 cited