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 by 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).

(S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements and Structural and Biological Investigation

Brogi S.
Primo
;
2018

Abstract

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 by 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).
Brogi, S.; Brindisi, M.; Butini, S.; Kshirsagar, G. U.; Maramai, S.; Chemi, G.; Gemma, S.; Campiani, G.; Novellino, E.; Fiorenzani, P.; Pinassi, J.; Aloisi, A. M.; Gynther, M.; Venskutonyte, R.; Han, L.; Frydenvang, K.; Kastrup, J. S.; Pickering, D. S.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/993349
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