TY - JOUR
T1 - The structure-based design of novel AMPA bioisosteres
AU - Burkhart, David J.
AU - Vij, Ashwani
AU - Natale, N. R.
N1 - Funding Information:
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.
PY - 1999/7
Y1 - 1999/7
N2 - 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.
AB - 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.
KW - AMPA antagonists
KW - Hydrazine and semicarbazide derivatives
KW - Isoxazoles
UR - http://www.scopus.com/inward/record.url?scp=0033236813&partnerID=8YFLogxK
U2 - 10.1023/A:1009544400552
DO - 10.1023/A:1009544400552
M3 - Article
AN - SCOPUS:0033236813
SN - 1074-1542
VL - 29
SP - 749
EP - 758
JO - Journal of Chemical Crystallography
JF - Journal of Chemical Crystallography
IS - 7
ER -