Synthesis and dopamine transporter affinity of 2-(methoxycarbonyl)-9-methyl-3-phenyl-9-azabicyclo[3.3.1]nonane derivatives

Zhengming Chen, Sari E Izenwasser, Jonathan L. Katz, Naijue Zhu, Cheryl L. Klein, Mark L. Trudell

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A series of 9-methyl-3β-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 μM) 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.

Original languageEnglish
Pages (from-to)4744-4749
Number of pages6
JournalJournal of Medicinal Chemistry
Volume39
Issue number24
StatePublished - Nov 22 1996
Externally publishedYes

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Azabicyclo Compounds
Dopamine Plasma Membrane Transport Proteins
Cocaine
Derivatives
Binding Sites
Tropanes
Stereochemistry
Putamen
X ray crystallography
X Ray Crystallography
Conformations
Rats
Nuclear magnetic resonance
Tissue
Ligands

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis and dopamine transporter affinity of 2-(methoxycarbonyl)-9-methyl-3-phenyl-9-azabicyclo[3.3.1]nonane derivatives. / Chen, Zhengming; Izenwasser, Sari E; Katz, Jonathan L.; Zhu, Naijue; Klein, Cheryl L.; Trudell, Mark L.

In: Journal of Medicinal Chemistry, Vol. 39, No. 24, 22.11.1996, p. 4744-4749.

Research output: Contribution to journalArticle

Chen, Zhengming ; Izenwasser, Sari E ; Katz, Jonathan L. ; Zhu, Naijue ; Klein, Cheryl L. ; Trudell, Mark L. / Synthesis and dopamine transporter affinity of 2-(methoxycarbonyl)-9-methyl-3-phenyl-9-azabicyclo[3.3.1]nonane derivatives. In: Journal of Medicinal Chemistry. 1996 ; Vol. 39, No. 24. pp. 4744-4749.
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