2-Carbomethoxy-3-aryl-8-oxabicyclo[3.2.1]octanes: Potent Non-Nitrogen Inhibitors of Monoamine Transporters

Citations Over TimeTop 13% of 1997 papers

Abstract

Cocaine is a potent stimulant of the mammalian central nervous system. Its reinforcing and stimulant properties have been associated with its propensity to bind to monoamine transporter systems. It has generally been assumed that the amino function on monoamines is a requirement for binding to monoamine transporters. In particular, the 8-amino function on the tropane skeleton of cocaine and cocaine analogs has been assumed to provide an ionic bond to the aspartic acid residue on the dopamine transporter (DAT). We have prepared the first 8-oxa analogs of the 3-aryltropanes (WIN compounds) and have found that the 3 beta-(3,4-dichlorophenyl) (6g) and 3 alpha-(3,4-dichlorophenyl) (7g) analogs are particularly potent (IC50 = 3.27 and 2.34 nM, respectively) inhibitors of the dopamine transporter. We now describe the synthesis and biology of the family of 2-carbomethoxy-3-aryl-8-oxabicyclo[3.2.1]octanes and demonstrate that an amino nitrogen is not required for binding to the DAT.

Related Papers

• → Is it all monoamines?(2009)6 cited
• → The Monoamine Hypothesis of Depression(2005)39 cited
• Progress in Sample Preparation and Analysis of Monoamine Neurotransmitters(2013)
• → <i>In situ</i> imaging of monoamine localization and dynamics by mass spectrometry(2022)
• → ChemInform Abstract: SYNTHESIS OF ARYL THIOCYANATES FROM ARYL ALKYL SULFIDES. CONVERSION OF UNACTIVATED ARYL HALIDES INTO ARYL THIOCYANATES(1983)