(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.

Research output: Contribution to journalJournal articleResearchpeer-review

Simone Brogi, Marghertia Brindisi, Stefania Butini, Giridhar Kshirsagar, Samuele Maramai, Giulia Chemi, Sandra Gemma, Giuseppe Campiani, Ettore Novellino, Paolo Fiorenzani, Jessica Pinassi, Anna Maria Aloisi, Mikko Gynther, Raminta Venskutonyte, Liwei Han, Karla Andrea Frydenvang, Jette Sandholm Jensen Kastrup, Darryl S Pickering

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).
Original languageEnglish
JournalJournal of Medicinal Chemistry
Volume61
Issue number5
Pages (from-to)2124-2130
Number of pages7
ISSN0022-2623
DOIs
Publication statusPublished - 8 Mar 2018

ID: 189836867