Synthesis, receptor binding and activity of iso and azakainoids

Wentian Wang, Dragan D. Simovic, Mingping Di, Lynne Fieber, Kathleen S. Rein

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Two syntheses for the production of an unsubstituted azakainoid are described. The 1,3-dipolar cycloaddition of diazomethane with trans-dibenzyl glutaconate yields a 1-pyrazoline, which may be reduced directly to the pyrazolidine. An unexpected trans-cis isomerization is observed during Hg/Al reduction of the 1-pyrazoline NN bond. Alternatively, when TMS diazomethane is used as the dipole, the resulting 2-pyrazoline obtained after desilylation may be reduced with NaCNBH3 to provide the trans azakainate analog exclusively. The synthesis of an unsubstituted isokainoid via Michael addition is also described. Glutamate receptor binding assays revealed that the azakaniod has a moderate affinity for unspecified glutamate receptors. Membrane depolarization of Aplysia neurons upon application of the azakainoid demonstrates that it is an ionotropic glutamate receptor agonist.

Original languageEnglish (US)
Pages (from-to)1949-1952
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number7
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

Keywords

  • Glutamate receptor
  • Kainoids
  • Receptor binding
  • Synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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