Synthetic Methodologies and SAR of Quinazoline Derivatives as PI3K Inhibitors

PI3K is an important anticancer target as it controls cellular functions such as growth, transformation, proliferation, motility and differentiation. Plasma cell cancer (multiple myeloma) occurs more than 10% among all haematological malignancies and accounts for 2% of all cancer-related deaths each year, it is mainly regulated by PI3K/AKT signaling cascade. Quinazoline derivatives have been reported as promising PI3K inhibitors. Lapatinib, afatinib, gefitinib, erlotinib, idelalisib and copanlisib are quinazoline-based, FDA-approved PI3K inhibitors, while compounds like NVPBYL719, GDC-0032, AZD8186, AZD-6482, etc. are under different stages of clinical trials. In light of the above-mentioned facts, in the present study, we have reported different synthetic approaches, mechanisms of anticancer action, and structure-activity relationship analysis of reported quinazoline derivatives as PI3K inhibitors to help researchers working in the field in designing better and isoform-selective PI3K inhibitors.

Automated summary

PI3K controls cellular functions and is an important target for anticancer treatment. Quinazoline derivatives have shown promise as PI3K inhibitors and several compounds are currently in clinical trials. This study provides information on synthetic approaches, mechanisms of action, and structure-activity relationship analysis of quinazoline derivatives to aid in the design of better and isoform-selective PI3K inhibitors for researchers in the field.