新型杂芳基二氢嘧啶衍生物作为非核苷乙型肝炎病毒抑制剂

StephenW

Chem Biol Drug Des. 2019 Mar 1. doi: 10.1111/cbdd.13512. [Epub ahead of print]
Design, Synthesis and Evaluation of Novel Heteroaryldihydropyrimidines Derivatives as Non-nucleoside Hepatitis B Virus Inhibitors by Exploring the Solvent-exposed Region.
Yu J1, Guo X2, Desta S1, Zhang S1, Zhang J1, Ding X1, Liang X2, Jia H3, Liu X1, Zhan P1.
Author information

1
    Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University,, 44 West Culture Road, 250012, Jinan, Shandong, PR China.
2
    Department of Immunology, Key Laboratory for Experimental, Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection and Immunology, Shandong University School of Medicine, Jinan, 250012, Shandong Province, PR China.
3
    School of Pharmacy, Weifang Medical University, 261053, Weifang, Shandong, PR China.

Abstract

In continuation of our efforts toward the discovery of potent non-nucleoside HBV inhibitors with novel structures, we have explored the solvent-exposed protein region of heteroaryldihydropyrimidines (HAPs) derivatives. Herein, the morpholine ring of GLS4 was replaced with substituted sulfonamides and triazoles to generate novel non-nucleoside HBV inhibitors with desirable potency. In in vitro biological evaluation, several derivatives showed good anti-HBV DNA replication activity compared to lamivudine. In particular, compound II-1 displayed the most potent activity against HBV DNA replication (IC50 = 0.35 ± 0.04 μM). The preliminary structure-activity relationships (SARs) of the new compounds were summarized, which may help in discovering more potent anti-HBV agents via rational drug design. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

HAP ; HBV ; capsid; protein-solvent interface; sulfonamide; triazoles

PMID:
    30825248
DOI:
    10.1111/cbdd.13512

StephenW

Chem Biol Drug Des。 2019年3月1日doi：10.1111 / cbdd.13512。 [印刷前的电子版]
新型杂芳基二氢嘧啶衍生物作为非核苷乙型肝炎病毒抑制剂的设计，合成和评价探索溶剂暴露区。
Yu J1，Guo X2，Desta S1，Zhang S1，Zhang J1，Ding X1，Liang X2，Jia H3，Liu X1，Zhan P1。
作者信息

1
    山东大学药学院药物化学系，化学生物学教育部重点实验室，山西省济南市西文化路44号，山东济南250012
2
    山东大学医学院免疫学教育部实验，畸形学重点实验室，山东省感染与免疫学重点实验室，山东济南250012
3
    潍坊医学院药学院，山东潍坊261053

抽象

在继续努力发现具有新结构的有效非核苷HBV抑制剂的过程中，我们研究了杂芳基二氢嘧啶（HAPs）衍生物的溶剂暴露蛋白区域。本文中，GLS4的吗啉环被取代的磺酰胺和三唑取代，以产生具有所需效力的新型非核苷HBV抑制剂。在体外生物学评估中，与拉米夫定相比，几种衍生物显示出良好的抗HBV DNA复制活性。特别是，化合物II-1显示出最有效的抗HBV DNA复制活性（IC50 = 0.35±0.04μM）。总结了新化合物的初步结构 - 活性关系（SAR），这可能有助于通过合理的药物设计发现更有效的抗HBV药物。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

HAP; HBV;衣壳;蛋白质 - 溶剂界面;磺胺;三唑

结论：
    30825248
DOI：
    10.1111 / cbdd.13512

乙肝人1949

这些文章，都是职称闹的，没有的文章一堆一堆的

newchinabok

乙肝人1949 发表于 2019-3-5 16:00
这些文章，都是职称闹的，没有的文章一堆一堆的

二，八现象，我一般看二的信息，八的都不看，没有多大价值

windu

吃屎都赶不上热的，别人二期，它遥遥无期，就是个笑话

hao2014

国内基本上就没有正二八百的原研药

青蒿素也是提炼的

502378774

回复 windu 的帖子

万事有个过程，至少在努力。尊重和理解，不行你上

9病成医

看了回帖，真为学术领域的不正之风无语了。