• Journal Article

3 alpha-(4'-substituted phenyl)tropane-2 beta-carboxylic acid methyl esters: novel ligands with high affinity and selectivity at the dopamine transporter

Citation

Holmquist, C., Keverline-Frantz, K. I., Abraham, P., Boja, J. W., Kuhar, M. J., & Carroll, F. (1996). 3 alpha-(4'-substituted phenyl)tropane-2 beta-carboxylic acid methyl esters: novel ligands with high affinity and selectivity at the dopamine transporter. Journal of Medicinal Chemistry, 39(21), 4139-4141.

Abstract

Since their initial preparation by Clarke and co-workers1 over 23 years ago, the 3?-(substituted phenyl)tropane-2?-carboxylic acid methyl ester class of compounds 1 have been widely employed in structure?activity relationship (SAR) studies at the cocaine binding site on the dopamine transporter (DAT).2 Since neither Clarke's nor any other reported method provided the 3?-phenyl analogs, the SAR studies did not include this isomer. Recently, we reported the synthesis of the first 3?-(substituted phenyl)tropane-2?-carboxylic acid methyl esters 2 by samarium iodide reduction of 3-aryl-2-carbomethoxytropenes 3.3 In this paper we describe a more efficient synthesis of several new 3?-(substituted phenyl)tropane-2?-carboxylic acid methyl esters 2 and present the results of the first monoamine transporter binding studies on this series of compounds.