Rational Design, Synthesis, and Biological Evaluation of 7‑Azaindole Derivatives as Potent Focused Multi-Targeted Kinase Inhibitors

Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tumorigenesis processes. Antiproliferative activity studies using different cellular models led to the discovery of a lead candidate (<b>6z</b>) that combined both antiangiogenic and antitumoral effects. The activity of <b>6z</b> was assessed against a panel of kinases and cell lines including solid cancers and leukemia cell models to explore its potential therapeutic applications. With its potency and selectivity for oncogenic kinases, <b>6z</b> was revealed to be a focused MTKI that should have a bright future in fighting a wide range of cancers