Synthesis, receptor binding and activity of iso and azakainoids

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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

Fingerprint

Diazomethane
Glutamate Receptors
Thermodynamic properties
Excitatory Amino Acid Agonists
Ionotropic Glutamate Receptors
Aplysia
Cycloaddition
Cycloaddition Reaction
Depolarization
Isomerization
Neurons
Assays
Membranes
glutaconic acid

Keywords

  • Glutamate receptor
  • Kainoids
  • Receptor binding
  • Synthesis

ASJC Scopus subject areas

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

Cite this

Synthesis, receptor binding and activity of iso and azakainoids. / Wang, Wentian; Simovic, Dragan D.; Di, Mingping; Fieber, Lynne A; Rein, Kathleen S.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 7, 01.04.2013, p. 1949-1952.

Research output: Contribution to journalArticle

Wang, Wentian ; Simovic, Dragan D. ; Di, Mingping ; Fieber, Lynne A ; Rein, Kathleen S. / Synthesis, receptor binding and activity of iso and azakainoids. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 7. pp. 1949-1952.
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