邻-(N-芳酰基-N-甲氨基苯)-二硫化合物的合成：通过N-甲基-2-单芳基苯并噻唑啉在溶剂中的自发偶联反应和它们的血管内皮生长因子抑制活性

N-甲基-2-单芳基苯并噻唑啉 (1) 在固体状态时可以稳定地储藏在空气中。但是，它们在不同溶剂中却表现出了不同的行为。在醇溶液或二甲亚砜-水的体系中，1相对稳定；而在其它有机溶剂如：丙酮，氯仿，二氯甲烷和乙酸乙酯等溶剂中，会发生自发偶联反应生成相应的邻-(N-芳酰基-N-甲氨基苯)-二硫化合物 (2)。对这些新的化合物 (1) 和 (2) 进行了体外人乳腺癌细胞 (MDA-MB-231) 血管内皮生长因子靶点筛选，大部分化合物都表现出了抑制活性。实验结果表明这两类化合物 (1) 和 (2) 作为血管内皮生长因子抑制剂值得进行深入研究。

Synthesis of o‐[N‐(Substituted benzoyl)‐ N‐methylamino]phenyl Disulfides by the Spontaneous Coupling of N‐Methyl‐2‐mono(substituted phenyl)benzothiazolines in Solution and Their VEGF Inhibitory Activities

The solid N‐methyl‐2‐mono(substituted phenyl)benzothiazolines ( 1 ) are stable and can be stored in atmosphere, whereas they present different behavior in different solvents. They are relatively stable in alcohol and DMSO‐H₂O. However, in other organic solvents such as acetone, CH₂Cl₂, CHCl₃, EtOAc etc., the oxidation‐coupling reactions occurred spontaneously to give the corresponding disulfide dimers 2 . The substituents at 2‐phenyl rings, reaction temperature and the acidities of the solutions exerted obvious impacts on the reaction rates and yields of 2 . 12 samples of N‐methyl‐2‐(substituted phenyl)benzothiazolines ( 1 ) and 11 dimers 2 were evaluated in vitro vascular endothelial growth factor (VEGF) inhibitory activity in human breast cancer cell MDA‐MB‐231 with 2‐methoxyestradiol (2‐ME) as the positive reference and most of them showed potent VEGF inhibitory activity with the EC₅₀ values of sub‐millimolar range. Among them, the compounds 1l , 1i , and 2d showed potent VEGF inhibitory activities and selectivities with EC₅₀ values of 0.07, <0.12, and 0.03 mmol/L and SI values of 25, >32 and >32, respectively, which were about 10 times of those of 2‐ME (EC₅₀=0.49 mmol/L, SI=3.37). The results further demonstrated that the scaffolds of 1 and 2 were privileged and merited further investigation as VEGF inhibitors.