Synthesis and pharmacological evaluation of several ring-contracted amantadine analogs

Bioorg Med Chem. 2008 Dec 1;16(23):9925-36. doi: 10.1016/j.bmc.2008.10.028. Epub 2008 Oct 17.

Abstract

The synthesis of several (3-noradamantyl)amines, [(3-noradamantyl)methyl]amines, (3,7-dimethyl-1-bisnoradamantyl)amines, and [(3,7-dimethyl-1-bisnoradamantyl)methyl]amines is reported. They were evaluated against a wide range of viruses and one of them inhibited the cytopathicity of influenza A virus at a concentration similar to that of amantadine. Several of the new polycyclic amines show an interesting activity as NMDA receptor antagonists. A rimantadine analogue displayed significant trypanocidal activity. Moreover, to further characterize the pharmacology of these compounds, their effects on dopamine uptake were also assessed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amantadine / analogs & derivatives*
  • Amantadine / chemical synthesis
  • Amantadine / pharmacology
  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology*
  • Cells, Cultured
  • Dogs
  • Dopamine / metabolism
  • Influenza A virus / drug effects
  • Inhibitory Concentration 50
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / chemistry
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Antiviral Agents
  • Receptors, N-Methyl-D-Aspartate
  • Amantadine
  • Dopamine