新型1,3,4-噻二嗪衍生物的合成与抗病毒活性

Synthesis and antiviral activity of novel 1,3,4-thiadiazine derivatives.

作者信息

Yang Yajun, Feng Ziming, Jiang Jianshuang, Yang Yanan, Pan Xiandao, Zhang Peicheng

机构信息

Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine (Ministry of Education), Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.

出版信息

Chem Pharm Bull (Tokyo). 2011;59(8):1016-9. doi: 10.1248/cpb.59.1016.

DOI:10.1248/cpb.59.1016

PMID:21804247

Abstract

A series of novel 1,3,4-thiadiazine derivatives were synthesized via chemical optimization on phthiobuzone. Their anti-herpes simplex virus (HSV) activities in vitro were also tested. Several compounds exhibited more highly potent anti-HSV activity and much higher selectivity index (SI) values than those of phthiobuzone. The most potent anti-HSV compound was 4f, which showed marked inhibition against HSV-1 (IC₅₀=77.04 µg/ml) and HSV-2 (IC₅₀=30.00 µg/ml). Meanwhile it had low cytotoxicity (CC₅₀=1000.00 µg/ml), resulting in high (SI(HSV-1)=12.98, SI(HSV-2)=33.33, respectively). Furthermore, a computational study for prediction of absorption, distribution, metabolism, excretion (ADME) properties of compound 4f was performed by determination of topological polar surface area, absorption and Lipinski parameters.

摘要

通过对酞磺胺噻唑进行化学优化合成了一系列新型1,3,4-噻二嗪衍生物。还测试了它们在体外的抗单纯疱疹病毒（HSV）活性。几种化合物表现出比酞磺胺噻唑更高的抗HSV活性和更高的选择性指数（SI）值。最有效的抗HSV化合物是4f，它对HSV-1（IC₅₀ = 77.04 µg/ml）和HSV-2（IC₅₀ = 30.00 µg/ml）表现出显著抑制作用。同时它具有低细胞毒性（CC₅₀ = 1000.00 µg/ml），导致高选择性指数（分别为SI(HSV-1)=12.98，SI(HSV-2)=33.33）。此外，通过测定拓扑极性表面积、吸收和Lipinski参数对化合物4f的吸收、分布、代谢、排泄（ADME）性质进行了计算研究。