Abstract
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 P \(\bar 1\).
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Burkhart, D.J., Vij, A. & Natale, N. The structure-based design of novel AMPA bioisosteres. Journal of Chemical Crystallography 29, 749–758 (1999). https://doi.org/10.1023/A:1009544400552
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DOI: https://doi.org/10.1023/A:1009544400552