Synthesis, biological activity, and absolute stereochemical assignment of NPS 1392: a potent and stereoselective NMDA receptor antagonist

Bioorg Med Chem Lett. 1999 Jul 19;9(14):1915-20. doi: 10.1016/s0960-894x(99)00317-0.

Abstract

The synthesis, biological activity, and single crystal X-ray structure of NPS 1392, (R)-(-)-3,3-bis(3-fluorophenyl)-2-methylpropan-1-amine (3a), a potent, stereoselective antagonist of the NMDA receptor, are described. The NMDA receptor selectively bound the levo isomer (3a) over its enantiomer (3b), which prompted a rigorous absolute configuration assignment. NPS 1392 has the R configuration based on the single-crystal X-ray diffraction analysis of the hydroiodide salt of NPS 1392. This compound is a potential neuroprotective agent for use in the treatment of ischemic stroke.

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Dizocilpine Maleate / pharmacology
  • Drug Evaluation, Preclinical
  • Excitatory Amino Acid Antagonists / pharmacology
  • Ischemia / drug therapy
  • Models, Molecular
  • Neuroprotective Agents / pharmacology
  • Propane / analogs & derivatives*
  • Propane / chemical synthesis
  • Propane / chemistry
  • Propane / pharmacology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*

Substances

  • Excitatory Amino Acid Antagonists
  • NPS 1392
  • Neuroprotective Agents
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Propane