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, Simone; Brindisi, Margherita; Butini, Stefania; Kshirsagar, Giridhar U.; Maramai, Samuele; Chemi, Giulia; Gemma, Sandra; Campiani, Giuseppe; Novellino, Ettore; Fiorenzani, Paolo; Pinassi, Jessica; Aloisi, Anna Maria; Gynther, Mikko; Venskutonytė, Raminta; Han, Liwei; Frydenvang, Karla; Kastrup, Jette Sandholm; Pickering, Darryl S.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 61:5(2018), pp. 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
Secondo
;
Novellino, Ettore;
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).
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 / Brogi, Simone; Brindisi, Margherita; Butini, Stefania; Kshirsagar, Giridhar U.; Maramai, Samuele; Chemi, Giulia; Gemma, Sandra; Campiani, Giuseppe; Novellino, Ettore; Fiorenzani, Paolo; Pinassi, Jessica; Aloisi, Anna Maria; Gynther, Mikko; Venskutonytė, Raminta; Han, Liwei; Frydenvang, Karla; Kastrup, Jette Sandholm; Pickering, Darryl S.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 61:5(2018), pp. 2124-2130. [10.1021/acs.jmedchem.8b00099]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/760623
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