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

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

Research output: Contribution to journalArticle

25 Scopus citations


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


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this