(2S, 4S)-2-amino-4-(2,2-diphenylethyl)pentanedioic acid selective group 2 metabotropic glutamate receptor antagonist

Abstract (2 S ,4 S )-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 a 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.