Synthesis and biological evaluation of a series of quinazoline-2-carboxylic acids and quinazoline-2,4-diones as glycine-NMDA antagonists: a pharmacophore model based approach.
The synthesis and glycine-NMDA binding activity of a series of quinazoline-2-carboxylic acids 1 and quinazoline-2,4-diones 2, containing all the essential and optional pharmacophoric descriptors required by a putative glycine antagonist model, are reported. The binding results show that only three of the title compounds displayed micromolar receptor affinity, demonstrating how disappointing the synthesis of receptor ligands based only on interaction models can be.
Colotta
V
V
Dipartimento di Scienze Farmaceutiche, Universita' di Firenze, Italy.
Catarzi
D
D
Varano
F
F
Cecchi
L
L
Filacchioni
G
G
Galli
A
A
Costagli
C
C
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate