We describe in this paper the synthesis of a novel series of anilino-2-quinazoline derivatives. These compounds have been screened against a panel of eight mammalian kinases and in parallel they were tested for cytotoxicity on a representative panel of seven cancer cell lines. One of them (DB18) has been found to be a very potent inhibitor of human “CDC2-like kinases” CLK1, CLK2 and CLK4, with IC₅₀ values in the 10–30 nM range. Interestingly, this molecule is inactive at 100 μM on the closely related “dual-specificity tyrosine-regulated kinase 1A” (DYRK1A). Extensive molecular simulation studies have been performed on the relevant kinases to explain the strong affinity of this molecule on CLKs, as well as its selectivity against DYRK1A.

我们在本文中描述了一系列新型苯胺基-2-喹唑啉衍生物的合成。这些化合物已针对一组八种哺乳动物激酶进行了筛选，并同时在一组具有代表性的七种癌细胞系上测试了它们的细胞毒性。其中之一 ( DB18 ) 已被发现是人类“CDC2 样激酶”CLK1、CLK2 和 CLK4 的非常有效的抑制剂，IC ₅₀值在 10-30 nM 范围内。有趣的是，该分子在 100 μM 时对密切相关的“双特异性酪氨酸调节激酶​​ 1A”（DYRK1A）无活性。已经对相关激酶进行了广泛的分子模拟研究，以解释该分子对 CLK 的强亲和力，以及它对 DYRK1A 的选择性。