title: Synthesis, receptor binding and activity of iso and azakainoids.
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.
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Str., Miami, FL 33199, USA.
authors.forename: Wentian
authors.initials: W
authors.lastname: Wang
authors.forename: Dragan D
authors.initials: DD
authors.lastname: Simovic
authors.forename: Mingping
authors.initials: M
authors.lastname: Di
authors.forename: Lynne
authors.initials: L
authors.lastname: Fieber
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Rein
mesh_terms: D000818:Animals; D001048:Aplysia; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D017470:Receptors, Glutamate / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001372:Aza Compounds; D017470:Receptors, Glutamate; D007608:Kainic Acid