Design and Synthesis of Diversity Oriented Pyrimidine Heterocycles As Anticancer Agents

Abstract

This research work encompassed in-silico assisted designing of novel ERK2 inhibitors. One of the top hits identified after rigorous computational exercises was further optimized to increase potency and binding affinity, resulting in two (8j and 10h) derivatives with sub-micromolar ERK2 inhibitory potential, along with optimal anti-proliferative activity. Overall, the work led to the identification of diverse pyrimidine based small molecule heterocycles as potent ERK2 inhibitors using in-silico approaches. This work may guide researchers in utilizing in-silico protocols to identify small molecule heterocycles for other targets. Also, researchers can carry forward exploration of these hits to develop more potent ERK2 inhibitors with anti-cancer potential.