ISOFORM-SELECTIVE MODULATORS FOR METABOTROPIC GLUTAMATE RECEPTORS ANDPROTEIN-KINASE-C - SYNTHESIS AND BIOLOGICAL EVALUATION

The synthetic studies for some known modulators of metabotropic glutam ate receptors (mGluRs) such as (S)-alpha M4CPG, (1S,3R)-ACPD, L-CCG-I are described. Based on the structure of alpha M4CPG several new confo rmationally constrained analogues are design ed and synthesized. Among them APICA is a selective antagonist for group II mGluRs. Also, a new benzolactam-V8 analogue is found to have better isoform-selectivity f or protein kinase C family. Three different protocols for synthesizing benzolactam-V8 analogues are developed to meet the requirement for de livering more analogues to test.