氨基甲酸酯类唾液酸转移酶抑制剂的设计、合成与活性评价

doi:10.5246/jcps.2020.01.003

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (1): 29-44.DOI: 10.5246/jcps.2020.01.003

氨基甲酸酯类唾液酸转移酶抑制剂的设计、合成与活性评价

颜婉君, 李文明, 熊德彩^*, 叶新山^*

北京大学医学部药学院天然药物及仿生药物国家重点实验室, 北京 100191

收稿日期:2019-05-28 修回日期:2019-09-24 出版日期:2020-01-21 发布日期:2019-11-13
通讯作者: Tel.: +86-10-82805732; +86-10-82805736, E-mail: decai@bjmu.edu.cn; xinshan@bjmu.edu.cn
基金资助:
The National Key R&D Program of China (Grant No. 2018YFA0507602), Project of National Science and Technology Major Project (Grant No. 2019ZX09301-106) and the National Natural Science Foundation of China (Grant No. 91853122).

Design, synthesis and evaluation of carbamate-containing sialyltransferase inhibitors

Wanjun Yan, Wenming Li, Decai Xiong^*, Xinshan Ye^*

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2019-05-28 Revised:2019-09-24 Online:2020-01-21 Published:2019-11-13
Contact: Tel.: +86-10-82805732; +86-10-82805736, E-mail: decai@bjmu.edu.cn; xinshan@bjmu.edu.cn
Supported by:
The National Key R&D Program of China (Grant No. 2018YFA0507602), Project of National Science and Technology Major Project (Grant No. 2019ZX09301-106) and the National Natural Science Foundation of China (Grant No. 91853122).

摘要/Abstract

摘要：

通过模拟磷酸连接的唾液酸胞苷单磷酸酯(CMP-Neu5Ac), 本文设计并合成了一系列氨基甲酸酯类唾液酸转移酶抑制剂。利用基于含紫外官能团受体的唾液酸转移酶抑制活性评价方法对化合物进行活性评价, 其中化合物15g显示出中等抑制活性。我们推测氨基甲酸酯有可能通过电子等排原理, 替换CMP-Neu5Ac中的磷酸酯基团, 改善其膜渗透性, 从而改善抑制活性。

关键词: 唾液酸转移酶抑制剂, 氨基甲酸酯, 设计, 合成

Abstract:

A series of carbamate-containing sialyltransferase inhibitors were designed and synthesized to simulate phosphate-linkedCMP-Neu5Ac. Their inhibitory activities were assayed against recombinant human ST3Gal I and ST6Gal I by using the Schmidt’sHPLC-based assay. The synthetic compound 15g showed moderate inhibitory activity. These findings implied that carbamate might serve as a bioisosteric replacement for a phosphate group in sialyltransferase inhibitor design to improve the membrane permeability.

Key words: Sialyltransferase inhibitor, Carbamate, Design, Synthesis

中图分类号:

R914

Supporting:

颜婉君, 李文明, 熊德彩, 叶新山. 氨基甲酸酯类唾液酸转移酶抑制剂的设计、合成与活性评价[J]. 中国药学(英文版), 2020, 29(1): 29-44.

Wanjun Yan, Wenming Li, Decai Xiong, Xinshan Ye. Design, synthesis and evaluation of carbamate-containing sialyltransferase inhibitors[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(1): 29-44.

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氨基甲酸酯类唾液酸转移酶抑制剂的设计、合成与活性评价

Design, synthesis and evaluation of carbamate-containing sialyltransferase inhibitors

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