Effects of two-carbon bridge region methoxylation of benztropine: discovery of novel chiral ligands for the dopamine transporter

Bioorg Med Chem Lett. 2001 Mar 26;11(6):823-7. doi: 10.1016/s0960-894x(01)00068-3.

Abstract

6-Methoxylated and 8-oxygenated benztropines were prepared and evaluated for their DAT and SERT activity (binding and uptake inhibition). Methoxylation at the two-carbon bridge of benztropine produced a novel class of potent and selective DAT ligands. An interesting enantioselectivity was also observed for this new class of chiral benztropines. The inactivity of the 8-oxygenated analogues seems to point out that, unlike cocaine and its analogues, interactions of benztropine ligands with DAT may be strongly governed by the nitrogen atom.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benztropine / chemistry
  • Benztropine / pharmacology*
  • Carrier Proteins / drug effects
  • Carrier Proteins / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Ligands
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Molecular Conformation
  • Muscarinic Antagonists / chemistry
  • Muscarinic Antagonists / pharmacology*
  • Nerve Tissue Proteins*
  • Structure-Activity Relationship

Substances

  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Ligands
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Muscarinic Antagonists
  • Nerve Tissue Proteins
  • Benztropine