The Synthesis of Novel Triazole Based MRCK Inhibitors

Cancer is a leading cause of deaths worldwide, so new treatment pathways are vital. Targeted therapies are one of many treatments for the disease. They can target proteins that are implicated in cancer metastasis. Myotonic dystrophy kinase-related CDC42-binding kinases (MRCK) are important central regulators of the actin-myosin cytoskeleton that contributes to tumour cell invasiveness and is a powerful driver of metastasis. MRCK inhibitors have been hypothesized to limit the invasive character of different cancers. Considering that there are only a handful MRCK inhibitors in the literature, the synthesis of novel MRCK is crucial to understand the function of the kinase as well as develop new therapeutics. Currently, BDP9066, is the most potent and selective MRCK inhibitor to date. Given this lead, we hypothesized that derivatized triazoles inhibitors would be as potent as BDP9066 while allowing for a diverse range of new inhibitors to be synthesized. These new MRCK inhibitors were synthesized using simple yet versatile sets of synthetic methods, allowing or rapid diversification of azaindole scaffolds.