Son of sevenless 1 (SOS1) is a vital guanine nucleotide exchange factor (GEFs) that activates rat sarcoma (Ras) protein in cells. SOS1 inhibitors can effectively inhibit the expression of downstream signaling pathways by blocking the interaction between SOS1 and Ras protein. Here, we designed and synthesized a series of quinazoline-based compounds, and conducted subsequent evaluations of their biological activities. Among them, the comparable compounds I-2 (IC₅₀ = 20 nM, against SOS1) I-5 (IC₅₀ = 18 nM, against SOS1) and I-10 (IC₅₀ = 8.5 nM, against SOS1) have kinase activity equivalent to BAY-293 (IC₅₀ = 6.6 nM, against SOS1), and I-10 also has cell activity equivalent to BAY-293, providing a theoretical reference for subsequent related researches on SOS1 inhibitors.

Son of sevenless 1 (SOS1) 是一种重要的鸟嘌呤核苷酸交换因子(GEF)，可激活细胞中的大鼠肉瘤 (Ras) 蛋白。SOS1抑制剂可通过阻断SOS1与Ras蛋白的相互作用，有效抑制下游信号通路的表达。在这里，我们设计并合成了一系列基于喹唑啉的化合物，并对其生物活性进行了后续评估。其中，比较化合物I-2（IC ₅₀  = 20 nM，针对 SOS1） I-5（IC ₅₀  = 18 nM，针对 SOS1）和I-10（IC ₅₀  = 8.5 nM，针对 SOS1）具有相当的激酶活性到BAY-293（IC ₅₀ = 6.6 nM, against SOS1)，I-10也具有与BAY-293相当的细胞活性，为后续SOS1抑制剂的相关研究提供理论参考。