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J Med Chem. 1998 Jun 18;41(13):2430-5.

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

Author information

1
Department of Chemistry, University of New Orleans, New Orleans, Louisiana 70148, USA.

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 (Ki) 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 (Ki = 5-96 microM) than cocaine and 2beta-(methoxycarbonyl)-3beta-phenyltropane (2, WIN 35,065-2). Surprisingly, the 3alpha-phenyl isomers (6c, 6d) were more potent than the 3beta-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 2beta-(methoxycarbonyl)-3-phenyltropanes.

PMID:
9632375
DOI:
10.1021/jm9705061
[Indexed for MEDLINE]

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