Identification of N-Benzyl 3,5-Dinitrobenzamides Derived from PBTZ169 as Antitubercular Agents,ACS Medicinal Chemistry Letters

当前位置： X-MOL 学术 › ACS Med. Chem. Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Identification of N-Benzyl 3,5-Dinitrobenzamides Derived from PBTZ169 as Antitubercular Agents
ACS Medicinal Chemistry Letters ( IF 3.5 ) Pub Date : 2018-06-26 00:00:00 , DOI: 10.1021/acsmedchemlett.8b00177
Linhu Li _{1,

2} , Kai Lv ₁ , Yupeng Yang ₃ , Jingquan Sun ₂ , Zeyu Tao ₁ , Apeng Wang ₁ , Bin Wang ₄ , Hongjian Wang ₁ , Yunhe Geng ₁ , Mingliang Liu ₁ , Huiyuan Guo ₁ , Yu Lu ₄

Affiliation

A series of benzamide scaffolds were designed and synthesized by the thiazinone ring opening of PBTZ169, and N-benzyl 3,5-dinitrobenzamides were finally identified as anti-TB agents in this work. 3,5-Dinitrobenzamides D5, 6, 7, and 12 exhibit excellent in vitro activity against the drug susceptive Mycobacterium tuberculosis H37Rv strain (MIC: 0.0625 μg/mL) and two clinically isolated multidrug-resistant strains (MIC < 0.016–0.125 μg/mL). Compound D6 displays acceptable safety and better pharmacokinetic profiles than PBTZ169, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.

中文翻译：

鉴定自PBTZ169衍生的N-苄基3,5-二硝基苯甲酰胺作为抗结核药

通过PBTZ169的噻嗪酮开环设计并合成了一系列苯甲酰胺支架，最终鉴定出N-苄基3,5-二硝基苯甲酰胺是抗结核药物。3,5- Dinitrobenzamides D5，6，7，和12表现出优异的体外对抗药物易感活性的结核分枝杆菌H37Rv的菌株（MIC：0.0625微克/毫升）和两个临床分离多药耐药性菌株（MIC <0.016-0.125微克/毫升）。化合物D6与PBTZ169相比，显示出可接受的安全性和更好的药代动力学特征，表明其有望成为未来抗结核药物发现的先导化合物。

更新日期：2018-06-26

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11