Bis(pentafluorosulfanyl)phenyl Azide as an Expeditious Tool for Click Chemistry toward Antitumor Pharmaceuticals
Bis(pentafluorosulfanyl)phenyl Azide as an Expeditious Tool for Click Chemistry toward Antitumor Pharmaceuticals
复制标题
双（五氟硫基）苯基叠氮化物作为点击化学抗肿瘤药物的快速工具
DOI：
10.1002/cmdc.201400059
复制
发表时间：
2014
期刊：
影响因子：
3.4
通讯作者：
N. Shibata
中科院分区：
文献类型：
--
作者：
Y.-D. Yang;E. Tokunaga;H. Akiyama;N. Saito;N. Shibata
在药剂中加入氟是一种公认的改善药剂类药性的方法。不同的取代基被用来引入氟，包括三氟甲基和三氟甲基硫基；然而，尽管五氟磺酰被认为是一种“超级”三氟甲基，但它的利用仍然相对不足。本文以炔和3,5 -二（五氟磺胺基）苯基叠氮为原料，通过咔嗒反应合成了一系列含1,4 -二取代- 1,2,3 -三唑，收率很高。研究了它们对人白血病单核细胞淋巴瘤U937细胞的生物学活性。特别是，1‐（3,5‐双（五氟磺胺基）苯基）‐4‐（4‐氟苯基）‐1H‐1,2,3‐三唑在浓度为60 μMand时，在细胞活力测定中表现出强大的功效，显示出激活caspase‐3活性，表明诱导细胞凋亡。类似的氟醇取代三唑对U937细胞也表现出良好的细胞毒性作用，ic50值为6.29 μM。鉴于这些初步结果，这些含五氟磺胺基的三唑为进一步开发新型抗肿瘤药物提供了有用的基础。
The inclusion of fluorine in pharmaceutical agents is a well‐ established means of improving their druglike properties. Different substituents have been used to introduce fluorine, including trifluoromethyl and trifluoromethylthio groups; however, the pentafluorosulfanyl remains relatively underutilized although it is considered to be a “super” trifluoromethyl group. Here, a series of pentafluorosulfanyl‐containing 1,4‐disubstituted‐1,2,3‐triazoles were synthesized by click reaction from alkynes and 3,5‐bis(pentafluorosulfanyl)phenyl azide in excellent yields. Their biological activities were evaluated against human leukemic monocyte lymphoma U937 cells. In particular, 1‐(3,5‐bis(pentafluorosulfanyl)phenyl)‐4‐(4‐fluorophenyl)‐1H‐1,2,3‐triazole exhibited potent efficacy in cell viability assays at a concentration of 60 μMand was shown to activate caspase‐3 activity, indicating induction of apoptosis. An analogous fluorenol‐substituted triazole also exhibited promising cytotoxic effects against U937 cells, with an IC50value of 6.29 μM. Given these preliminary results, these pentafluorosulfanyl‐containing triazoles represent useful building blocks for the further development of novel antitumor agents.