Development of 3-substituted-1H-indole derivatives as NR2B/NMDA receptor antagonists.
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.
Gitto
Rosaria
R
Dipartimento Farmaco-Chimico, Università di Messina, Messina, Italy. rgitto@pharma.unime.it
De Luca
Laura
L
Ferro
Stefania
S
Citraro
Rita
R
De Sarro
Giovambattista
G
Costa
Lara
L
Ciranna
Lucia
L
Chimirri
Alba
A
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
D000927:Anticonvulsants; D007211:Indoles; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate