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., et al. (2018). (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. JOURNAL OF MEDICINAL CHEMISTRY, 61(5), 2124-2130 [10.1021/acs.jmedchem.8b00099].

(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

Brindisi, Margherita;Butini, Stefania
;
Maramai, Samuele;Chemi, Giulia;Gemma, Sandra;Campiani, Giuseppe
;
Fiorenzani, Paolo;Aloisi, Anna Maria;
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., et al. (2018). (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. JOURNAL OF MEDICINAL CHEMISTRY, 61(5), 2124-2130 [10.1021/acs.jmedchem.8b00099].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/1035550