Design, Synthesis and Biological Evaluation of Quinazoline SOS1 Inhibitors
Hongyu Jiang 1, Yiqing Fan 1, Xia Wang 1, Jie Wang 1, Haifan Yang 1, Weizheng Fan 2, Chunlei Tang 3

Boy of sevenless 1 (SOS1) is a crucial guanine nucleotide exchange factor (GEFs) that activates rat sarcoma (Ras) protein in cells. SOS1 inhibitors can effectively hinder the expression of downstream signaling pathways by blocking the interaction between SOS1 and Ras protein. Here, we designed and synthesized a number of quinazoline-based compounds, and conducted subsequent evaluations of the biological activities. Included in this, the comparable compounds I-2 (IC50=20nM, against SOS1) I-5 (IC50=18nM, against SOS1) and that i-10 (IC50=8.5nM, against SOS1) have kinase activity equal to BAY-293 (IC50=6.6nM, against SOS1), and that i-10 also offers cell activity equal to BAY-293, supplying a theoretical reference for subsequent related researches on SOS1 inhibitors.