Design, synthesis, and activity of novel cis- and trans-3,6-disubstituted pyran biomimetics of 3,6-disubstituted piperidine as potential ligands for the dopamine transporter

Bioorg Med Chem Lett. 2003 May 5;13(9):1591-5. doi: 10.1016/s0960-894x(03)00169-0.

Abstract

In our effort to develop novel molecules for the dopamine transporter, we converted our previously designed dopamine transporter specific 3,6-disubstituted piperidine template into corresponding pyran derivatives. cis-Pyran derivative 7b, like their piperidine counterparts, exhibited greater activity for the dopamine transporter compared to the trans-isomer. Further molecular modifications of the cis derivative led to the development of potent analogues which indicated successful bioisosteric replacement of the piperidine ring by a pyran moiety in these 3,6-disubstituted derivatives.

Publication types

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

MeSH terms

  • Animals
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors / chemical synthesis*
  • Dopamine Uptake Inhibitors / chemistry
  • Dopamine Uptake Inhibitors / pharmacology
  • Ligands
  • Membrane Glycoproteins*
  • Membrane Transport Proteins / metabolism*
  • Nerve Tissue Proteins*
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Pyrans / chemical synthesis*
  • Pyrans / chemistry
  • Pyrans / pharmacology
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Ligands
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Piperidines
  • Pyrans
  • Dopamine