FMS样受体酪氨酸激酶3（FLT3）的过度表达和异常激活，与急性髓性白血病（AML）的发生、发展及不良预后密切相关。目前临床用于AML治疗的药物均为多靶点激酶抑制剂，存在选择性差、毒副作用大，治疗窗口窄等缺陷。因此，开发高效低毒的新型FLT3选择性小分子抑制剂对于AML的治疗具有重要的现实意义。前期研究通过对Sunitinib进行结构改造，获得了活性和选择性优于Sunitinib的化合物SN-D05，但是成药性尚有待提高。为了解决先导化合物SN-D05存在的化学稳定性差、体内药效不强、耐受性不高等问题，本项目将在前期研究基础上，采用生物电子等排和分子杂合的策略，借助计算机辅助药物设计的方法，以成药性为导向，对先导化合物进行结构优化，并通过体内外的生物活性筛选，期望获得1-2个结构新颖、安全高效、成药性好的新型FLT3抑制剂，为AML的治疗提供新的候选药物。

The excessive expression and aberrant activation of Fms-like tyrosine kinase-3 (FLT3) are closely related to the occurrence, development and poor prognosis of acute myeloid leukemia. Current drugs for the clinical treatment of AML are multiple target kinase inhibitors which exist the defects of poor selectivity, significant side effects and narrow therapeutic window. Therefore, the development of novel selective FLT3 inhibitors with high efficiency and low toxicity is of great practical significance for the treatment of AML. In previous studies, compound SN-D05 with better activity and selectivity was obtained through the structural modification of Sunitinib. However, the druggability remains to be improved. In order to improve the poor chemical stability, weak in vivo efficacy and low tolerance, we will focus on the structure optimization of lead compound SN-D05 using the strategy of bioisosterism and molecular hybridization, with the aid of computer assistant drug design. And the biological activity will be evaluated in vitro and in vivo. Our goal is to discovery 1-2 novel FLT3 inhibitors with high efficiency, low toxicity, broad therapeutic window and better druggability. The successful completion of this study will provide new drug candidates for the treatment of AML.