Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease

被引：11

作者：

Damalanka, Vishnu C. ^{[1
]}

Kim, Yunjeong ^{[2
]}

Kankanamalage, Anushka C. Galasiti ^{[1
]}

Lushington, Gerald H. ^{[3
]}

Mehzabeen, Nurjahan ^{[4
]}

Battaile, Kevin P. ^{[5
]}

Lovell, Scott ^{[4
]}

Chang, Kyeong-Ok ^{[2
]}

Groutas, William C. ^{[1
]}

机构：

[1] Wichita State Univ, Dept Chem, Wichita, KS 67260 USA

[2] Kansas State Univ, Dept Diagnost Med & Pathobiol, Coll Vet Med, Manhattan, KS 66506 USA

[3] LiS Consulting, Lawrence, KS 66046 USA

[4] Univ Kansas, Prot Struct Lab, Lawrence, KS 66047 USA

[5] APS Argonne Natl Lab, Hauptman Woodward Med Res Inst, IMCA CAT, Argonne, IL 60439 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 127卷

基金：

美国国家卫生研究院;

关键词：

Macrocyclic inhibitors; Norovirus; 3CLprotease; SUBSTRATE-SPECIFICITY; CELL-PERMEABILITY; GASTROENTERITIS; RULE; OPTIMIZATION; CANDIDATES; DISCOVERY; FOODBORNE; CYSTEINE; TARGETS;

D O I：

10.1016/j.ejmech.2016.12.033

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Norovirus infections have a major impact on public health worldwide, yet there is a current dearth of norovirus-specific therapeutics and prophylactics. This report describes the discovery of a novel class of macrocyclic inhibitors of norovirus 3C-like protease, a cysteine protease that is essential for virus replication. SAR, structural, and biochemical studies were carried out to ascertain the effect of structure on pharmacological activity and permeability. Insights gained from these studies have laid a solid foundation for capitalizing on the therapeutic potential of the series of inhibitors described herein. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：41 / 61

页数：21

共 62 条

[1] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].

Adams, Paul D. ;

Afonine, Pavel V. ;

Bunkoczi, Gabor ;

Chen, Vincent B. ;

Davis, Ian W. ;

Echols, Nathaniel ;

Headd, Jeffrey J. ;

Hung, Li-Wei ;

Kapral, Gary J. ;

Grosse-Kunstleve, Ralf W. ;

McCoy, Airlie J. ;

Moriarty, Nigel W. ;

Oeffner, Robert ;

Read, Randy J. ;

Richardson, David C. ;

Richardson, Jane S. ;

Terwilliger, Thomas C. ;

Zwart, Peter H. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :213-221

[2] Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space [J].

Alex, Alexander ;

Millan, David S. ;

Perez, Manuel ;

Wakenhut, Florian ;

Whitlock, Gavin A. .

MEDCHEMCOMM, 2011, 2 (07) :669-674

[3] PICORNAVIRAL 3C CYSTEINE PROTEINASES HAVE A FOLD SIMILAR TO CHYMOTRYPSIN-LIKE SERINE PROTEINASES [J].

ALLAIRE, M ;

CHERNAIA, MM ;

MALCOLM, BA ;

JAMES, MNG .

NATURE, 1994, 369 (6475) :72-76

[4]

[Anonymous], 2012, J WOMENS MED

[5] Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial [J].

Atmar, Robert L. ;

Baehner, Frank ;

Cramer, Jakob P. ;

Song, Eric ;

Borkowski, Astrid ;

Mendelman, Paul M. .

JOURNAL OF INFECTIOUS DISEASES, 2016, 214 (06) :845-853

[6] Global Economic Burden of Norovirus Gastroenteritis [J].

Bartsch, Sarah M. ;

Lopman, Benjamin A. ;

Ozawa, Sachiko ;

Hall, Aron J. ;

Lee, Bruce Y. .

PLOS ONE, 2016, 11 (04)

[7] The burden of norovirus gastroenteritis: an important foodborne and healthcare-related infection [J].

Belliot, G. ;

Lopman, B. A. ;

Ambert-Balay, K. ;

Pothier, P. .

CLINICAL MICROBIOLOGY AND INFECTION, 2014, 20 (08) :724-730

[8] Lead discovery and optimization strategies for peptide macrocycles [J].

Bhat, Abhijit ;

Roberts, Lee R. ;

Dwyer, John J. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 94 :471-479

[9] Probing the Physicochemical Boundaries of Cell Permeability and Oral Bioavailability in Lipophilic Macrocycles Inspired by Natural Products [J].

Bockus, Andrew T. ;

Lexa, Katrina W. ;

Pye, Cameron R. ;

Kalgutkar, Amit S. ;

Gardner, Jarret W. ;

Hund, Kathryn C. R. ;

Hewitt, William M. ;

Schwochert, Joshua A. ;

Glassey, Emerson ;

Price, David A. ;

Mathiowetz, Alan M. ;

Liras, Spiros ;

Jacobson, Matthew P. ;

Lokey, R. Scott .

JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (11) :4581-4589

[10] Norovirus Gastroenteritis in Immunocompromised Patients [J].

Bok, Karin ;

Green, Kim Y. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (22) :2126-2132

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