State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, PR China.
Bioorg Med Chem Lett. 2012 Dec 1;22(23):7114-8. doi: 10.1016/j.bmcl.2012.09.070. Epub 2012 Oct 2.
A series of 5,6-dihydroxypyrimidine analogs were synthesized and evaluated for their anti-HIV activity in vitro. Among all of the analogs, several compounds exhibited significant anti-HIV activity, especially 1b and 1e, which showed the most potent anti-HIV activity with EC(50) values of 0.14 and 0.15 μM, and TI (therapeutic index) values of >300 and >900, respectively. Further docking studies revealed that the representative compounds 1e and 3a could meet the HIV-1 integrase inhibition minimal requirements of a chelating domain (two metal ions) and an aromatic domain (π-π stacking interactions).
一系列 5,6-二羟基嘧啶类似物被合成并在体外评估其抗 HIV 活性。在所有类似物中，几种化合物表现出显著的抗 HIV 活性，特别是 1b 和 1e，它们表现出最强的抗 HIV 活性，EC(50)值分别为 0.14 和 0.15 μM，TI（治疗指数）值分别为 >300 和 >900。进一步的对接研究表明，代表性化合物 1e 和 3a 可以满足 HIV-1 整合酶抑制的最小要求，包括一个螯合域（两个金属离子）和一个芳香域（π-π 堆积相互作用）。
