奥芬达唑质控标准中关键杂质成分的合成

引用本文: 李钊, 冯佳, 高媛媛, 李波, 朱维良, 陈凯先. 奥芬达唑质控标准中关键杂质成分的合成[J]. 应用化学, 2016, 33(9): 1061-1066. doi: 10.11944/j.issn.1000-0518.2016.09.150434 shu

Citation: LI Zhao, FENG Jia, GAO Yuanyuan, LI Bo, ZHU Weiliang, CHEN Kaixian. Synthesis of Key Impurities as Quality Control Standards of Oxfendazole[J]. Chinese Journal of Applied Chemistry, 2016, 33(9): 1061-1066. doi: 10.11944/j.issn.1000-0518.2016.09.150434 shu

奥芬达唑质控标准中关键杂质成分的合成

李钊 ^a,b, ,
冯佳 ^b,c, ,
高媛媛 ^a,b, ,
李波 ^{b,
,} ,
朱维良 ^{b,
,} ,
陈凯先 ^a,b,

1.
a 上海中医药大学上海 201203;
2.
b 中国科学院上海药物研究所上海 201203;
3.
c 中国科学技术大学纳米科学技术学院江苏苏州 215123

通讯作者: 李波,博士;Tel:021-50806600-5318;E-mail:boli@simm.ac.cn;研究方向:药物设计与合成共同;朱维良,研究员;Tel:021-50805020;E-mail:wlzhu@simm.ac.cn;研究方向:药物设计与合成; 李波,博士;Tel:021-50806600-5318;E-mail:boli@simm.ac.cn;研究方向:药物设计与合成共同;朱维良,研究员;Tel:021-50805020;E-mail:wlzhu@simm.ac.cn;研究方向:药物设计与合成

基金项目:
国家自然科学基金（81273435，81302699)

上海市自然科学基金（14ZR1447800）资助项目

摘要: 苯并咪唑氨基甲酸酯类化合物（Benzimidazolecarbamate，BZC）是一类广谱抗寄生虫抗菌剂，其广泛使用的典型代表药物为奥芬达唑。但该药物中的杂质化合物不易获得，导致生产质控不足。本文发现了奥芬达唑中4种主要杂质成分，包括芬苯达唑、5-苯磺酰基-1H-2-甲氧甲酰氨基苯并咪唑、5-苯亚磺酰基-1H-2-氨基苯并咪唑和2-二（5-苯亚磺酰基-1H-2-苯并咪唑基）-碳酰二胺的简单高效化学合成方法。特别是通过两种不同的关环策略实现了关键吡唑环的有效合成，以及控制氧化条件得到硫醚的亚砜和砜的氧化产物。该方法不仅可为奥芬达唑的质控提供标准品，而且为基于奥芬达唑类似物的新型杀虫、抗菌及抗肿瘤等药物的研发提供了一条简单高效的合成线路。

关键词:

奥芬达唑
/ 杂质
/ 标准品
/ 合成

English

Synthesis of Key Impurities as Quality Control Standards of Oxfendazole

1.
a Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
2.
b Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
3.
c Nano Science and Technology Institute, University of Science and Technology of China, Suzhou, Jiangsu 215123, China

Corresponding author: 李波,博士;Tel:021-50806600-5318;E-mail:boli@simm.ac.cn;研究方向:药物设计与合成共同;朱维良,研究员;Tel:021-50805020;E-mail:wlzhu@simm.ac.cn;研究方向:药物设计与合成; 李波,博士;Tel:021-50806600-5318;E-mail:boli@simm.ac.cn;研究方向:药物设计与合成共同;朱维良,研究员;Tel:021-50805020;E-mail:wlzhu@simm.ac.cn;研究方向:药物设计与合成

Received Date: 08 December 2015
Fund Project:
国家自然科学基金（81273435，81302699)

上海市自然科学基金（14ZR1447800）资助项目

Abstract: Oxfendazole, a benzimidazolecarbamate(BZC) compound, is a broad-spectrum antihelmintic and antimicrobial agent. The insufficient sources of its impurities affected the quality control of the product. Herein, a simple and efficient method for synthesis of four impurities, fenbendazole, methyl (5-(phenylsulfonyl)-1H-benzo[d]imidazol-2-yl)carbamate, 5-(phenylsulfinyl)-1H-benzo[d]imidazol-2-amine and 1,3-bis(5-(phenylsulfinyl)-1H-benzo[d]imidazol-2-yl)urea, is revealed. Especially, the key imidazole ring was constructed efficiently via two different strategies. Furthermore, oxidative products of sulfur ether, sulphone and sulfoxide were obtained by controlling oxidative conditions. This method not only increases the source of the standard substances for quality control of oxfendazole, but also provides an efficient synthetic strategy to prepare the novel antihelmintic, antimicrobial and antitumor agents based on oxfendazol.

Key words:

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沈阳化工大学材料科学与工程学院沈阳 110142

奥芬达唑质控标准中关键杂质成分的合成

English

Synthesis of Key Impurities as Quality Control Standards of Oxfendazole

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

奥芬达唑质控标准中关键杂质成分的合成

English

Synthesis of Key Impurities as Quality Control Standards of Oxfendazole

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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