N′-取代苯基-2-苯并噻唑磺酰脲类化合物的合成  

Synthesis of N'-substituted phenyl-2-benzothiazolesulfonylureas derivatives

作　　者：贾心语 苗娜[2] 马丽娟[1] 钱宇[1] 巴俊杰[1] 程卯生[3] 

机构地区：[1]内蒙古医科大学药学院,内蒙古呼和浩特010110 [2]内蒙古巴彦淖尔市医院,内蒙古临河015002 [3]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2013年第6期467-472,共6页Chinese Journal of Medicinal Chemistry

摘　　要：目的为寻找具有抗肿瘤活性的新化合物,设计合成一系列N'-取代苯基-2-苯并噻唑磺酰脲类化合物。方法以2-巯基苯并噻唑为原料,经弱氧化、氨化、再氧化得到2-苯并噻唑磺酰胺;各种取代苯胺与三光气反应制得一系列取代苯异氰酸酯;2-苯并噻唑磺酰胺与各种取代苯异氰酸酯反应,得到一系列N'-取代苯基-2-苯并噻唑磺酰脲类化合物。结果与结论合成了15个N'-取代苯基-2-苯并噻唑磺酰脲类化合物,除化合物6b外其余14个未见文献报道。目标化合物的结构均经IR、1H-NMR和MS确证。初步体外活性筛选结果表明,目标化合物6b、6e、6n有一定的抗肿瘤活性,进一步的抗肿瘤活性测试正在进行中。Diarylsulfonylureas exhibit broad-spectrum antitumor activity against several solid tumors such as the colon, ovary, and lung tumors. According to the relationships between their structural characteristics and antitumor activity, fifteen N＇-substituted phenyl-2-benzothiazolesulfonylureas derivatives （6a - 60） were de- signed and synthesized. First of all ,2-benzothiazolesulfenamide was prepared from 2-mercapto benzothiazole by oxidation and amination. 2-Benzothiazolesulfonamide was prepared from 2-benzothiazolesulfenamide by oxidation with potassium permanganate. Then a series of substituted phenylisocyanates were prepared from a variety of substituted anilines by reacting with triphosgene （BTC）. Finally, the target compounds were ob- tained by the condensation of 2-benzothiazolesulfonamide with a variety of substituted phenylisocyanates. The structures of target compounds were confirmed by IR,1H-NMR and ESI-MS. Among them, fourteen compounds were first reported in this paper. The evaluation of in vitro antitumor activity showed that target compounds 6b,6e and 6n displayed inhibitory activities to a certain degree against tested human non-small cell lung cancer cell A-549.

关 键 词：N′-取代苯基-2-苯并噻唑磺酰脲类化合物 合成 抗肿瘤活性 

分 类 号：TQ463[化学工程—制药化工]