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

doi:10.1016/j.ejmech.2016.12.033

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

Abstract

Norovirus infections have a major impact on public health worldwide, yet there is a current dearth of norovirus-specific therapeutics and prophylactics. Furthermore, 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.

Authors:

Damalanka, Vishnu C. ^[1]; Kim, Yunjeong ^[2]; Galasiti Kankanamalage, Anushka C. ^[1]; Lushington, Gerald H. ^[3]; Mehzabeen, Nurjahan ^[4]; Battaile, Kevin P. ^[5]; Lovell, Scott ^[4]; Chang, Kyeong-Ok ^[2]; Groutas, William C. ^[1]

Wichita State Univ., KS (United States)
Kansas State Univ., Manhattan, KS (United States)
LiS Consulting, Lawrence, KS (United States)
Univ. of Kansas, Lawrence, KS (United States)
Argonne National Lab. (ANL), Argonne, IL (United States)

Publication Date:: 2016-12-21

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health; National Inst. of General Medical Sciences

OSTI Identifier:: 1368274

Alternate Identifier(s):: OSTI ID: 1416192

Grant/Contract Number:: AC02-06CH11357; AI109039; P30GM110761

Resource Type:: Accepted Manuscript

Journal Name:: European Journal of Medicinal Chemistry

Additional Journal Information:: Journal Volume: 127; Journal Issue: C; Journal ID: ISSN 0223-5234

Publisher:: Elsevier

Country of Publication:: United States

Language:: ENGLISH

Subject:: 59 BASIC BIOLOGICAL SCIENCES; Macrocyclic inhibitors; Norovirus; 3CLprotease

Citation Formats


                    Damalanka, Vishnu C., Kim, Yunjeong, Galasiti Kankanamalage, Anushka C., Lushington, Gerald H., Mehzabeen, Nurjahan, Battaile, Kevin P., Lovell, Scott, Chang, Kyeong-Ok, and Groutas, William C. Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease.  United States: N. p., 2016. 
        Web.  doi:10.1016/j.ejmech.2016.12.033.

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                    Damalanka, Vishnu C., Kim, Yunjeong, Galasiti Kankanamalage, Anushka C., Lushington, Gerald H., Mehzabeen, Nurjahan, Battaile, Kevin P., Lovell, Scott, Chang, Kyeong-Ok, & Groutas, William C. Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease.  United States.  doi:10.1016/j.ejmech.2016.12.033.

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                    Damalanka, Vishnu C., Kim, Yunjeong, Galasiti Kankanamalage, Anushka C., Lushington, Gerald H., Mehzabeen, Nurjahan, Battaile, Kevin P., Lovell, Scott, Chang, Kyeong-Ok, and Groutas, William C. Wed .  
        "Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease".  United States.  doi:10.1016/j.ejmech.2016.12.033.  https://www.osti.gov/servlets/purl/1368274.

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@article{osti_1368274,

  title        = {Design, synthesis, and evaluation of a novel series of macrocyclic inhibitors of norovirus 3CL protease},

  author       = {Damalanka, Vishnu C. and Kim, Yunjeong and Galasiti Kankanamalage, Anushka C. and Lushington, Gerald H. and Mehzabeen, Nurjahan and Battaile, Kevin P. and Lovell, Scott and Chang, Kyeong-Ok and Groutas, William C.},

  abstractNote = {Norovirus infections have a major impact on public health worldwide, yet there is a current dearth of norovirus-specific therapeutics and prophylactics. Furthermore, 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.},

  doi          = {10.1016/j.ejmech.2016.12.033},

  journal      = {European Journal of Medicinal Chemistry},

  number       = C,

  volume       = 127,

  place        = {United States},

  year         = {2016},

  month        = {12}

}

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DOI: 10.1016/j.ejmech.2016.12.033

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Cited by: 4 works

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Works referencing / citing this record:

Norovirus antivirals: Where are we now?
journal, December 2018

Netzler, Natalie E.; Enosi Tuipulotu, Daniel; White, Peter A.
Medicinal Research Reviews, Vol. 39, Issue 3
DOI: 10.1002/med.21545

Piperidine carbamate peptidomimetic inhibitors of the serine proteases HGFA, matriptase and hepsin
journal, January 2019

Damalanka, Vishnu C.; Wildman, Scott A.; Janetka, James W.
MedChemComm, Vol. 10, Issue 9
DOI: 10.1039/c9md00234k

Antiviral Drug Discovery: Norovirus Proteases and Development of Inhibitors
journal, February 2019

Chang, Kyeong-Ok; Kim, Yunjeong; Lovell, Scott
Viruses, Vol. 11, Issue 2
DOI: 10.3390/v11020197

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

Abstract

Citation Formats

Norovirus antivirals: Where are we now? journal, December 2018

Piperidine carbamate peptidomimetic inhibitors of the serine proteases HGFA, matriptase and hepsin journal, January 2019

Antiviral Drug Discovery: Norovirus Proteases and Development of Inhibitors journal, February 2019

Norovirus antivirals: Where are we now?
journal, December 2018

Piperidine carbamate peptidomimetic inhibitors of the serine proteases HGFA, matriptase and hepsin
journal, January 2019

Antiviral Drug Discovery: Norovirus Proteases and Development of Inhibitors
journal, February 2019