TY - JOUR
T1 - (S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements, Structural and Biological Investigation.
AU - Brogi, Simone
AU - Brindisi, Marghertia
AU - Butini, Stefania
AU - Kshirsagar, Giridhar
AU - Maramai, Samuele
AU - Chemi, Giulia
AU - Gemma, Sandra
AU - Campiani, Giuseppe
AU - Novellino, Ettore
AU - Fiorenzani, Paolo
AU - Pinassi, Jessica
AU - Aloisi, Anna Maria
AU - Gynther, Mikko
AU - Venskutonyte, Raminta
AU - Han, Liwei
AU - Frydenvang, Karla Andrea
AU - Kastrup, Jette Sandholm Jensen
AU - Pickering, Darryl S
PY - 2018/3/8
Y1 - 2018/3/8
N2 - Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1 and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip).
AB - Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1 and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip).
U2 - 10.1021/acs.jmedchem.8b00099
DO - 10.1021/acs.jmedchem.8b00099
M3 - Journal article
C2 - 29451794
VL - 61
SP - 2124
EP - 2130
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 5
ER -