Synthesis and transporter binding properties of 2,3-diphenyltropane stereoisomers. Comparison to 3beta-phenyltropane-2beta-carboxylic acid esters

J Med Chem. 1997 Apr 11;40(8):1247-51. doi: 10.1021/jm960703k.

Abstract

2beta,3beta-Diphenyl-(5), 2alpha,3alpha-diphenyl-(6), and 2alpha,3beta-diphenyltropane (3) as well as 2,3-diphenyltrop-2-ene (4) were prepared in racemic form and assayed for inhibition of radioligand binding at the dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporters. Among all three transporters, compounds 4-6 bound the DA transporter with the highest affinity. The 2beta,3beta-diphenyltropane (5) bound the DA transporter with an IC50 value (28 nM) almost identical to that of 3beta-phenyltropane-2beta-carboxylic acid methyl ester (WIN 35,065-2) and has much greater selectivity relative to binding to the serotonin transporter. A comparison of the radioligand data from this study to radioligand data obtained on other WIN 35,065-2 analogs suggests that hydrophobicity of the C-2 substituent of some analogs of the WIN 35,065-2 class may be an important contributing factor to binding at the DA transporter.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding, Competitive
  • Carrier Proteins / metabolism
  • Cocaine / analogs & derivatives*
  • Cocaine / chemistry
  • Cocaine / metabolism
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins / metabolism
  • Norepinephrine / metabolism
  • Norepinephrine Plasma Membrane Transport Proteins
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • Stereoisomerism
  • Structure-Activity Relationship
  • Symporters*

Substances

  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Norepinephrine Plasma Membrane Transport Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Symporters
  • Serotonin
  • troparil
  • Cocaine
  • Dopamine
  • Norepinephrine