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新型流感聚合酶 PB2 抑制剂治疗甲型流感感染。

Novel influenza polymerase PB2 inhibitors for the treatment of influenza A infection.

机构信息

Center for AIDS Research, Global Virus Network, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.

Center for AIDS Research, Global Virus Network, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.

出版信息

Bioorg Med Chem Lett. 2019 Oct 15;29(20):126639. doi: 10.1016/j.bmcl.2019.126639. Epub 2019 Aug 24.

DOI:10.1016/j.bmcl.2019.126639
PMID:31493987
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7732027/
Abstract

Exploration of the chemical space of known influenza polymerase PB2 inhibitor Pimodivir, was performed by our group. We synthesized and identified compounds 16a and 16b, two novel thienopyrimidine derivatives displaying anti-influenza A activity in the single digit nanomolar range in cell culture. Binding of these unique compounds in the influenza polymerase PB2 pocket was also determined using molecular modeling.

摘要

本课题组对已有的流感聚合酶 PB2 抑制剂 Pimodivir 进行了化学空间探索。我们合成并鉴定了两个新型噻吩并嘧啶衍生物 16a 和 16b，它们在细胞培养中显示出抗甲型流感活性，其半数抑制浓度（IC50）均在纳摩尔数量级。同时，还通过分子建模确定了这些独特化合物在流感聚合酶 PB2 口袋中的结合情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/557394e48a94/nihms-1539188-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/3ec561f02856/nihms-1539188-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/345f0b5ce0c9/nihms-1539188-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/cd647aee8279/nihms-1539188-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/75872d69fccd/nihms-1539188-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/44045307e0a3/nihms-1539188-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/3e653dfbeff2/nihms-1539188-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/5ac4aa70662f/nihms-1539188-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/95d580d92e42/nihms-1539188-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/557394e48a94/nihms-1539188-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/3ec561f02856/nihms-1539188-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/345f0b5ce0c9/nihms-1539188-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/cd647aee8279/nihms-1539188-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/75872d69fccd/nihms-1539188-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/44045307e0a3/nihms-1539188-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/3e653dfbeff2/nihms-1539188-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/5ac4aa70662f/nihms-1539188-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/95d580d92e42/nihms-1539188-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cf6/7732027/557394e48a94/nihms-1539188-f0009.jpg

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本文引用的文献

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N Engl J Med. 2018 Sep 6;379(10):913-923. doi: 10.1056/NEJMoa1716197.
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