State Key lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, People's Republic of China.
Mol Divers. 2012 Aug;16(3):579-90. doi: 10.1007/s11030-012-9390-1. Epub 2012 Aug 14.
An environmentally friendly and mild Bischler cyclization was developed to access quinazolines with diverse substitution. Based on this method, a library of 53 quinazoline derivatives was prepared and tested in vitro for cytotoxicity and inhibition on T-cell and B-cell proliferation. Compounds 6b, 7b, 17b, 33, and 35 showed higher inhibitory activity on both T-cell and B-cell proliferations, with IC(50) values of 6.16, 6.30, 5.43, 2.54, and 9.80 μM on T-cell, respectively. All the tested compounds showed no obvious cytotoxicity at 10 μM concentration. The preliminary structure-activity relationship was concluded revealing that 4-position is the key modification site for potent quinazoline immunosuppressive agent.
开发了一种环保且温和的 Bischler 环化反应，以获得具有多种取代基的喹唑啉。基于该方法，制备了 53 种喹唑啉衍生物库，并对其进行了体外细胞毒性和对 T 细胞和 B 细胞增殖抑制的测试。化合物 6b、7b、17b、33 和 35 对 T 细胞和 B 细胞的增殖均显示出更高的抑制活性，其对 T 细胞的 IC50 值分别为 6.16、6.30、5.43、2.54 和 9.80μM。所有测试化合物在 10μM 浓度下均没有明显的细胞毒性。初步的构效关系表明，4-位是具有强效喹唑啉免疫抑制剂的关键修饰位点。
