A3- and A2B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection,RSC Medicinal Chemistry

当前位置： X-MOL 学术 › RSC Med. Chem. › 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.)

A3- and A2B-nitrocorroles: synthesis and antiviral activity evaluation against human cytomegalovirus infection
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2020-05-19 , DOI: 10.1039/d0md00034e
Léo Bucher _{1,

2,

3,

4,

5} , Sandrine Kappler-Gratias _{5,

6,

7,

8} , Nicolas Desbois _{1,

2,

3,

4,

5} , Kerstin Bystricky _{9,

10,

11,

12,

13} , Franck Gallardo _{5,

6,

7,

8} , Claude P. Gros _{1,

2,

3,

4,

5}

Affiliation

Human cytomegalovirus (hCMV) is responsible for several pathologies impacting immunocompromised patients and can trigger life-threatening infection. Several antivirals are available and are used in the clinic, but hCMV resistant strains have appeared and patients have encountered therapeutic failure. Hence, there is a constant need for new best in class or first in class antiviral molecules. We have previously shown that nitrocorroles could be used as a potent anti-hCMV agent without acute toxicity in mice. They therefore represent an excellent platform to perform structure–activity relationship (SAR) studies and to increase efficiency or reduce toxicity. We have generated original A₂B- and A₃-substituted nitrocorroles and have discovered optimized compounds with selectivity indices above 200. These compounds are easily synthesized in only one to two-step reactions; they are up-scalable and cost efficient. They are therefore excellent candidates for hCMV therapies and they pave the way for a new generation of molecules.

中文翻译：

A3-和A2B-硝基皮质醇：针对人类巨细胞病毒感染的合成和抗病毒活性评估

人类巨细胞病毒（hCMV）是影响免疫功能低下患者的几种病理原因，并可能引发威胁生命的感染。有几种抗病毒药物可供临床使用，但出现了hCMV耐药株，患者治疗失败。因此，不断需要新的一流或一流的抗病毒分子。先前我们已经表明，硝基皮质醇可以用作有效的抗hCMV药物，而不会在小鼠中引起急性毒性。因此，它们是进行结构与活性关系（SAR）研究并提高效率或降低毒性的绝佳平台。我们生成了原始的A ₂ B-和A ₃取代的硝基酚，发现了选择性指数高于200的优化化合物。这些化合物仅需一到两步即可轻松合成；它们是可扩展的且具有成本效益。因此，它们是hCMV治疗的极佳候选者，并为新一代分子铺平了道路。

更新日期：2020-07-22

点击分享查看原文

点击收藏

阅读更多本刊最新论文