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

[41] SOLVENT CONTENT OF PROTEIN CRYSTALS [J].

MATTHEWS, BW .

JOURNAL OF MOLECULAR BIOLOGY, 1968, 33 (02) :491-+

[42] Phaser crystallographic software [J].

McCoy, Airlie J. ;

Grosse-Kunstleve, Ralf W. ;

Adams, Paul D. ;

Winn, Martyn D. ;

Storoni, Laurent C. ;

Read, Randy J. .

JOURNAL OF APPLIED CRYSTALLOGRAPHY, 2007, 40 :658-674

[43] Improving Drug Candidates by Design: A Focus on Physicochemical Properties As a Means of Improving Compound Disposition and Safety [J].

Meanwell, Nicholas A. .

CHEMICAL RESEARCH IN TOXICOLOGY, 2011, 24 (09) :1420-1456

[44] Human Norovirus as a Foodborne Pathogen: Challenges and Developments [J].

Moore, Matthew D. ;

Goulter, Rebecca M. ;

Jaykus, Lee-Ann .

ANNUAL REVIEW OF FOOD SCIENCE AND TECHNOLOGY, VOL 6, 2015, 6 :411-433

[45] Structural Basis of Substrate Specificity and Protease Inhibition in Norwalk Virus [J].

Muhaxhiri, Zana ;

Deng, Lisheng ;

Shanker, Sreejesh ;

Sankaran, Banumathi ;

Estes, Mary K. ;

Palzkill, Timothy ;

Song, Yongcheng ;

Prasad, B. V. Venkataram .

JOURNAL OF VIROLOGY, 2013, 87 (08) :4281-4292

[46]

Orchard R.C., 2016, SCIENCE, V10, P1126

[47] Genome of Emerging Norovirus GII.17, United States, 2014 [J].

Parra, Gabriel I. ;

Green, Kim Y. .

EMERGING INFECTIOUS DISEASES, 2015, 21 (08) :1477-1479

[48] Developments in the CCP4 molecular-graphics project [J].

Potterton, L ;

McNicholas, S ;

Krissinel, E ;

Gruber, J ;

Cowtan, K ;

Emsley, P ;

Murshudov, GN ;

Cohen, S ;

Perrakis, A ;

Noble, M .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 :2288-2294

[49] Antiviral targets of human noroviruses [J].

Prasad, B. V. Venkataram ;

Shanker, Sreejesh ;

Muhaxhiri, Zana ;

Deng, Lisheng ;

Choi, Jae-Mun ;

Estes, Mary K. ;

Song, Yongcheng ;

Palzkill, Timothy ;

Atmar, Robert L. .

CURRENT OPINION IN VIROLOGY, 2016, 18 :117-125

[50] Noroviruses: epidemiology, immunity and prospects for prevention [J].

Pringle, Kimberly ;

Lopman, Benjamin ;

Vega, Everardo ;

Vinje, Jan ;

Parashar, Umesh D. ;

Hall, Aron J. .

FUTURE MICROBIOLOGY, 2015, 10 (01) :53-67

← 1 2 3 4 5 6 7 →