3α-(4‘-Substituted phenyl)tropane- 2β-carboxylic Acid Methyl Esters:  Novel Ligands with High Affinity and Selectivity at the Dopamine Transporter

Journal of Medicinal Chemistry
1996.0

Abstract

Since their initial preparation by Clarke and coworkers1 over 23 years ago, the 3â-(substituted phenyl) tropane-2â-carboxylic acid methyl ester class of compounds 1 have been widely employed in structureactivity 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 3R-phenyl analogs, the SAR studies did not include this isomer. Recently, we reported the synthesis of the first 3R-(substituted phenyl)tropane-2â-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 3R-(substituted phenyl)tropane-2â-carboxylic acid methyl esters 2 and present the results of the first monoamine transporter binding studies on this series of compounds.

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