Design, synthesis, and biological evaluation of tricyclic heterocycle-tetraamine conjugates as potent NMDA channel blockers

Bioorg Med Chem Lett. 2007 Sep 1;17(17):4729-32. doi: 10.1016/j.bmcl.2007.06.069. Epub 2007 Jun 27.

Abstract

We have developed a new class of N-methyl-d-aspartate (NMDA) channel blockers having a conjugate structure that consists of a nitrogenous heterocyclic head and a tetraamine tail. Among them, dihydrodibenzazepine-homospermine conjugate (8) exhibited potent antagonistic activity at NR1/NR2A or NR1/NR2B NMDA subtype receptors compared with the lead compound, AQ343 (1), or memantine, as well as weak cytotoxicity. Its superior biological profiles compared with known compounds point to its potential use as therapeutic agents for neurological disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Chemistry, Pharmaceutical / methods*
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Excitatory Amino Acid Antagonists / chemical synthesis*
  • Excitatory Amino Acid Antagonists / chemistry
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*

Substances

  • Amines
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate