Molecular Optimization of Benzimidazole Scaffolds for Targeted Protein Kinase Inhibition in Oncology

Abstract

Benzimidazole is one of the most prestigious heterocyclic motifs, with a variety of biological applications. Over the years, diverse benzimidazole hybrids have proved single or multi‐protein kinase inhibitory activity. Some examples were approved by the Food and Drug Administration (FDA) for use in the treatment regimens of certain types of cancers, other benzimidazole‐based protein kinase inhibitors are still in clinical trials. Additionally, different research groups have employed different approaches for the design of novel benzimidazole hybrids targeting protein kinases in oncology. In the current review article, a comprehensive overview is provided on the incorporation of the benzimidazole scaffold in FDA‐approved drugs, as well as in clinical trial candidates being developed as protein kinase inhibitors for cancer treatment. Additionally, recent advances in rational design strategies, molecular modeling, protein kinase inhibition, antiproliferative activity, and structure–activity relationships (SAR) of novel benzimidazole‐based hybrids targeting single or multiple kinases are summarized.