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 P1.
| Original language | English |
|---|---|
| Pages (from-to) | 749-758 |
| Number of pages | 10 |
| Journal | Journal of Chemical Crystallography |
| Volume | 29 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1999 |
Funding
We would like to thank Dr. Gary Knerr for his assistance on the spectroscopic characterization of these compounds and Dr. Jason Stenzel for his ongoing advice and support. The Bruker (formerly Siemens) SMART CCD diffraction facility was established at the University of Idaho with the assistance of the NSF-EPSCoR program under NSF OSR-9350539 and the M.J. Murdock Charitable Trust, Vancouver, WA.
| Funders | Funder number |
|---|---|
| OSR-9350539 | |
| ARC Centre of Excellence in Cognition and its Disorders |
Keywords
- AMPA antagonists
- Hydrazine and semicarbazide derivatives
- Isoxazoles