Combined Strategies for the Discovery of Ionotropic Glutamate Receptor Antagonists

• Published in: ChemMedChem Vol. 4; no. 6; pp. 917 - 922
• Main Authors: Chimirri, Alba, De Luca, Laura, Ferro, Stefania, De Sarro, Giovanbattista, Ciranna, Lucia, Gitto, Rosaria
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 08.06.2009; WILEY‐VCH Verlag
• Subjects: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - chemistry; AMPA; antagonists; Anticonvulsants - chemistry; Drug Discovery; Excitatory Amino Acid Antagonists - chemistry; molecular modeling; N-Methylaspartate - chemistry; Neuroprotective Agents - chemistry; NR2B/NMDA; receptors; Receptors, Glutamate - chemistry; Receptors, Glutamate - metabolism
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.200900109

New glutamate receptor ligands: This review describes the discovery of rationally designed AMPA and NMDA receptor antagonists, some of which have been proven to be highly potent anticonvulsant and neuroprotective agents. This review summarizes the results of our research group engaged in the development of new glutamate receptor ligands. Chemical and biological studies of several active molecules have been carried out. In particular, extensive work has addressed the identification of antagonists of AMPA and NMDA receptor subtypes using a combination of computational strategies. Innovative synthetic pathways have been used and small libraries of new molecules prepared. In vitro and in vivo tests were performed, and some compounds proved to be highly potent anticonvulsant and neuroprotective agents. New glutamate receptor ligands: This review describes the discovery of rationally designed AMPA and NMDA receptor antagonists, some of which have been proven to be highly potent anticonvulsant and neuroprotective agents.