Divergent Strategy for the Synthesis of Indolopyrazines Fused to Benzopyrimidinones and Benzimidazoles: Identification of Antiproliferative Molecules

Abstract

AbstractDespite the continued efforts and advancements in anti‐cancer drug discovery, cancer is still considered as one of the leading causes of mortality globally. Hence, the discovery of novel chemotherapeutic agents that displayed a prominent effect against cancer is a pressing need. In this study, an expeditious cascade was used to access a pilot library of indolopyrazine fused to imidazole and pyrimidinone heterocyclic scaffolds. The synthetic strategy utilized a cascade reaction that combined Mannich with aza‐Michael addition reactions followed by coupling with a variety of amines. Phenotypic screening of the developed library against HCT116 colon and MCF‐7 breast cancer cell lines identified chemotypes that formed the basis for hit‐to‐lead development of anti‐cancer agents. The intriguing architecture and scope of functional variability of these types of pentacyclic molecules made them appropriate motifs for the development of lead drug candidates.