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HCV 抑制剂研究进展:非结构多聚蛋白的重要性。

A review on HCV inhibitors: Significance of non-structural polyproteins.

机构信息

Department of Pharmaceutical Chemistry, Vishnu Institute of Pharmaceutical Education and Research, Narsapur, Medak, Telangana, 502313, India.

Department of Chemistry, School of Science, GITAM deemed to be University, Rudraram, Patancheru Mandal, Hyderabad, Telangana, Sangareddy Dist. 502329, India.

出版信息

Eur J Med Chem. 2019 Feb 15;164:576-601. doi: 10.1016/j.ejmech.2018.12.045. Epub 2018 Dec 31.

Abstract

Hepatitis C virus (HCV) mortality and morbidity is a world health misery with an approximate 130-150 million chronically HCV tainted and suffering individuals and it initiate critical liver malfunction like cirrhosis, hepatocellular carcinoma or liver HCV cancer. HCV NS5B protein one of the best studied therapeutic target for the identification of new drug candidates to be added to the combination or multiple combination medication recently approved. During the past few years, NS5B has thus been an important object of attractive medicinal chemistry endeavors, which induced to the surfacing of betrothal preclinical drug molecules. In this scenario, the current review set limit to discuss research published on NS5B and few other therapeutic functional inhibitors concentrating on hit investigation, hit to lead optimization, ADME parameters evaluation, and the SAR data which was out for each compound type and similarity taken into consideration. The discussion outlined in this specific review will surly helpful and vital tool for those medicinal chemists investigators working with HCV research programs mainly pointing on NS5B and set broad spectrum identification of creative anti HCV compounds. This mini review also tells each and every individual compound ability related how much they are active against NS5B and few other targets.

摘要

丙型肝炎病毒 (HCV) 的死亡率和发病率是全球健康的一大难题,全球约有 1.3 亿至 1.5 亿慢性 HCV 感染患者,他们会出现严重的肝脏功能障碍,如肝硬化、肝细胞癌或 HCV 肝癌。HCV NS5B 蛋白是研究最深入的治疗靶点之一,目的是确定新的药物候选物,以添加到最近批准的联合或多种联合用药中。在过去的几年中,NS5B 一直是有吸引力的药物化学研究的重要对象,这促使了订婚前临床前药物分子的出现。在这种情况下,目前的综述仅限于讨论关于 NS5B 和其他一些治疗功能抑制剂的研究,重点是对命中化合物的调查、命中化合物到先导化合物的优化、ADME 参数评估,以及考虑每个化合物类型和相似性的 SAR 数据。这篇综述的讨论将为那些从事 HCV 研究项目的药物化学家调查人员提供有用的和重要的工具,主要针对 NS5B 和广谱鉴定创新的抗 HCV 化合物。这篇小型综述还介绍了每个化合物针对 NS5B 和其他几个靶点的活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccd6/7185800/17eef140a8a4/fx1_lrg.jpg

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