RESUMEN
2-(9-Xanthylmethyl)-2-(2'-carboxycyclopropyl) glycine 6e is a novel metabotropic glutamate receptor antagonist. A series of alpha, C-3' disubstituted (carboxycyclopropyl)glycines 6f-n were prepared. Antagonist activity was observed for all these compounds at group 2 and group 3 mGluRs. Although they were slightly less active on group 2 mGluRs than non C-3' substituted 6e, the compounds 6f-n were more selective with lesser or no activity on group 1 mGluR subtypes (IC50 values greater than 100 microns).
Asunto(s)
Antagonistas de Aminoácidos Excitadores/síntesis química , Glicina/análogos & derivados , Receptores de Glutamato/efectos de los fármacos , Animales , Línea Celular , Ciclopropanos/química , Ciclopropanos/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Glicina/química , Glicina/farmacología , Humanos , Concentración 50 Inhibidora , Neuronas/efectos de los fármacos , Prosencéfalo/efectos de los fármacos , Ratas , Relación Estructura-ActividadRESUMEN
(2S,4S)-2-Amino-4-(4,4-diphenylbut-1-yl)-pentane-1,5-dioic acid 1m, is a novel metabotropic glutamate receptor (mGluR) antagonist with insignificant ionotropic affinity. It is selective antagonist of negatively-coupled cAMP-linked mGluRs with no effect on phosphoinositide coupled mGluRs. A series of 4-substituted glutamic acid analogues were prepared and it was found that compound 1k is tenfold more potent than 1m. Compound 1k has neither significant affinity for ionotropic glutamate receptors nor group 1 and 3 metabotropic receptors.
