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

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.

doi:10.1016/j.ejmech.2016.12.033

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

Journal Article · Wed Dec 21 00:00:00 UTC 2016 · European Journal of Medicinal Chemistry

DOI: https://doi.org/10.1016/j.ejmech.2016.12.033 · OSTI ID:1368274

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)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Inst. of General Medical Sciences; National Inst. of Health; USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1368274

Journal Information:: European Journal of Medicinal Chemistry, Journal Name: European Journal of Medicinal Chemistry Journal Issue: C Vol. 127; ISSN 0223-5234

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES
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