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:
-
- 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:
- Research Org.:
- Argonne National Laboratory (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.
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. https://doi.org/10.1016/j.ejmech.2016.12.033
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. https://doi.org/10.1016/j.ejmech.2016.12.033. https://www.osti.gov/servlets/purl/1368274.
@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 = {Wed Dec 21 00:00:00 EST 2016},
month = {Wed Dec 21 00:00:00 EST 2016}
}
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