title: Development of 3-substituted-1H-indole derivatives as NR2B/NMDA receptor antagonists.
abstract: A combined ligand-based and structure-based approach has previously allowed us to identify NR2B/NMDA receptor antagonists containing indole scaffold. In order to further explore the main structure activity relationships of this class of derivatives we herein report the design, synthesis and biological evaluation of new analogues. Some derivatives demonstrated to produce significant anticonvulsant properties and NMDA antagonism. The most active of them (3d) showed NR2B binding affinity equipotent to that of ifenprodil. These results were also corroborated by computational studies.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Messina, Italy. rgitto@pharma.unime.it
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferro
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.forename: Lara
authors.initials: L
authors.lastname: Costa
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciranna
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D015195:Drug Design; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D008958:Models, Molecular; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D007211:Indoles; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate