Pharmacophore modeling as an efficient tool in the discovery of novel noncompetitive AMPA receptor antagonists.
A three-dimensional pharmacophore model for the binding of noncompetitive AMPA receptor antagonists was developed in order to map common structural features of highly active compounds. This hypothesis, which consists of two hydrophobic regions, one hydrogen bond acceptor and one aromatic region, was successfully used as framework for the design of a new class of allosteric modulators containing a tetrahydroisoquinoline skeleton and for in silico screening. The promising biological results suggested that the identified molecules might be useful "lead compounds" for future drug development.
Barreca
Maria Letizia
ML
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. barreca@pharma.unime.it
Gitto
Rosaria
R
Quartarone
Silvana
S
De Luca
Laura
L
De Sarro
Giovambattista
G
Chimirri
Alba
A
D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology; D017076:Computer-Aided Design; D015195:Drug Design; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D018091:Receptors, AMPA