Structure-based design and synthesis of macrocyclic human rhinovirus 3C protease inhibitors

被引：10

作者：

Namoto, Kenji ^{[1
]}

Sirockin, Finton ^{[1
]}

Sellner, Holger ^{[1
]}

Wiesmann, Christian ^{[1
]}

Villard, Frederic ^{[1
]}

Moreau, Robert J. ^{[2
]}

Valeur, Eric ^{[1
,3
]}

Paulding, Stephanie C. ^{[1
]}

Schleeger, Simone ^{[1
]}

Schipp, Kathrin ^{[1
]}

Loup, Joachim ^{[1
]}

Andrews, Lori ^{[2
]}

Swale, Ryann ^{[2
]}

Robinson, Michael ^{[2
]}

Farady, Christopher J. ^{[1
]}

机构：

[1] Novartis Inst BioMed Res, Novartis Campus, CH-4002 Basel, Switzerland

[2] Novartis Inst BioMed Res, 5300 Chiron Way, Emeryville, CA 94608 USA

[3] AstraZeneca, IMED Biotech Unit, Med Chem Cardiovasc & Metab Dis, Gothenburg, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 05期

关键词：

Rhinovirus 3C protease; Protease inhibition; Covalent inhibitor; Macrocycle; Structure-based drug design; Solid phase synthesis; VITRO ANTIVIRAL ACTIVITY; BIOLOGICAL EVALUATION; DISCOVERY;

D O I：

10.1016/j.bmcl.2018.01.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The design and synthesis of macrocyclic inhibitors of human rhinovirus 3C protease is described. A macrocyclic linkage of the P1 and P3 residues, and the subsequent structure-based optimization of the macrocycle conformation and size led to the identification of a potent biochemical inhibitor 10 with sub-micromolar antiviral activity. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：906 / 909

页数：4

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