Synthetic Methodologies and SAR of Quinazoline Derivatives as PI3K Inhibitors

Author(s):

Aditya Raj, Adarsh Kumar, Ankit Kumar Singh, Harshwardhan Singh, Suresh Thareja and Pradeep Kumar*   Pages 1013 - 1047 ( 35 )

Abstract:

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.

Keywords:

Cancer, quinazoline, PI3K, SAR, mechanism of action, mTOR pathways.

Affiliation:

Graphical Abstract:

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