The structure-based design of novel AMPA bioisosteres

David J. Burkhart, Ashwani Vij, N. R. Natale

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The reaction of 4-acetyl-5-methyl-3-isoxazolyl carboxylate with a variety of hydrazines and semicarbazides yielded molecules which are viable antagonist candidates for the AMPA receptor. Molecular modeling studies used in conjunction with the x-ray crystal structures of these derivatives show a close correlation between the hydrogen bonding characteristics of AMPA with that of the hydrazone and semicarbazone isoxazole derivatives. Uncyclized hydrazones and semicarbazones (1-5) were formed by using corresponding hydrazines and semicarbazides containing strong electron withdrawing groups to prevent cyclization with the ethyl ester. The crystals of 1 are orthorhombic with a = 14.2997(3), b = 15.4112(4), c = 16.0153(4) Å, Z = 8, and space group Pbca; 2 monoclinic with a = 19.738(2), b = 10.4155(7), c = 15.583(1) Å, β = 92.348(2)°, Z = 8, and space group C2/c; 3 triclinic with a = 8.3365(5), b = 8.4930(5), c = 12.2379(7) Å, α = 92.568(2), β = 102.229(2), γ = 104.449(1)°, Z = 2, and space group P1.

Original languageEnglish
Pages (from-to)749-758
Number of pages10
JournalJournal of Chemical Crystallography
Issue number7
StatePublished - Jul 1999


  • AMPA antagonists
  • Hydrazine and semicarbazide derivatives
  • Isoxazoles


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