Synthesis and dopamine transporter affinity of the four stereoisomers of (±)-2-(methoxycarbonyl)-7-methyl-3-phenyl-7-azabicyclo[2.2.1]heptane

C. Zhang, S. Izenwasser, J. L. Katz, P. D. Terry, M. L. Trudell

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

All four stereoisomers of (±)-2-(methoxycarbonyl)-7-methyl-3-phenyl-7- azabicyclo[2.2.1]heptane were synthesized and evaluated as cocaine binding site ligands at the dopamine transporter. The in vitro binding affinities (K(i)) of the 7-azabicyclo[2.2.1]heptane derivatives were measured in rat caudate-putamen tissue and found to be 100-3000-fold less potent (K(i) = 5- 96 μM) than cocaine and 2β-(methoxycarbonyl)-3β-phenyltropane (2, WIN 35,065-2). Surprisingly, the 3α-phenyl isomers (6c, 6d) were more potent than the 3β-phenyl isomers (6a, 6b). Molecular modeling studies revealed that the rigid 7-azabicyclo[2.2.1]heptane derivatives possess molecular topologies which are significantly different than the molecular topologies of the 2β(methoxycarbonyl)-3-phenyltropanes.

Original languageEnglish (US)
Pages (from-to)2430-2435
Number of pages6
JournalJournal of Medicinal Chemistry
Volume41
Issue number13
DOIs
StatePublished - Jun 18 1998
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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