二芳基脲衍生物的合成及作为 FLT3 抑制剂的生物评价。
Synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors.
机构信息
School of Pharmaceutical Science, Jiangnan University, Wuxi, China.
School of Pharmaceutical Science, Jiangnan University, Wuxi, China.
出版信息
Bioorg Med Chem Lett. 2020 Dec 1;30(23):127525. doi: 10.1016/j.bmcl.2020.127525. Epub 2020 Sep 6.
As a class III receptor tyrosine kinase (RTK), FMS-like tyrosine kinase 3 (FLT3) is always overexpressed in many cases of acute leukemia. This paper studies the structure-based synthesis and biological evaluation of diaryl urea derivatives as FLT3 inhibitors. Encouragingly, compounds 15b, 16b, 24a, and 24c showed excellent biological activities in a low nanomolar range. In particular, compound 16b demonstrated significant inhibitory potency against FLT3-ITD (IC = 5.60 nM) and better antiproliferative activity than quizartinib against MV4-11 cell line (IC = 0.176 nM). It is indicated that compound 16b for the treatment of acute myeloid leukemia could be very promising.
作为一种 III 类受体酪氨酸激酶 (RTK)，FMS 样酪氨酸激酶 3 (FLT3) 在许多急性白血病病例中总是过度表达。本文研究了作为 FLT3 抑制剂的二芳基脲衍生物的基于结构的合成和生物学评价。令人鼓舞的是，化合物 15b、16b、24a 和 24c 在纳摩尔级的低浓度范围内表现出优异的生物学活性。特别是，化合物 16b 对 FLT3-ITD（IC=5.60 nM）具有显著的抑制效力，并且对 MV4-11 细胞系的增殖活性优于奎扎替尼（IC=0.176 nM）。这表明化合物 16b 可能是治疗急性髓细胞白血病的很有前途的药物。
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