156774-35-5Relevant articles and documents
The Discovery of an Unusually Selective and Novel Cocaine Analog: Difluoropine. Synthesis and Inhibition of Binding at Cocaine Recognition Sites
Meltzer, Peter C.,Liang, Anna. Y.,Madras, Bertha. K.
, p. 2001 - 2010 (1994)
Cocaine is a stimulant drug with a high abuse liability. Although it inhibits several monamine transporters in the mammalian brain, its primary mechanism of action has been ascribed to its inhibition of the dopamine transporter. The synthesis, characterization, and receptor binding properties of all eight isomers of a unique tropane analog, 2-carbomethoxy-3-tropane is described. In addition, we report that the S-enantiomer, (S)-(+)-2β-carbomethoxy-3α-tropane, Difluoropine, is a potent (IC50 10.9 nM) and selective (324 ) ligand for the dopamine transporter.
Enantioselective synthesis of S-(+)-2β-carboalkoxy-3α-[bis(4-fluorophenyl)methoxy]tropanes as novel probes for the dopamine transporter
Zou, Mu-Fa,Agoston, Gregory E.,Belov, Yuri,Kopajtic, Theresa,Katz, Jonathan L.,Newman, Amy Hauck
, p. 1249 - 1252 (2007/10/03)
Synthesis of a series of pure S-(+)-2β-carboalkoxy-3α-[bis(4-fluorophenyl)methoxy]tropanes (>99% ee) was achieved by employing a chiral amine-induced asymmetric reaction of tropinone with methyl cyanoformate as the key step. In this series, all of the S-(+)-enantiomers were 2-fold more potent than their racemic mixtures and all displayed high-affinity binding for DAT (Ki=13-40 nM). These data support previous findings of significant divergence in structural requirements for high-affinity DAT binding among tropane-based inhibitors. Furthermore, the 2-substituent in the 3α-[bis(4-fluorophenyl)methoxy]tropane series is well tolerated at the DAT but not at SERT (Ki=690-2040 nM), or muscarinic M1 receptors (Ki=133-4380 nM) resulting in highly selective DAT ligands that may provide new leads toward a cocaine-abuse therapeutic.
