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J Med Chem. 2016 Mar 10;59(5):1899-913. doi: 10.1021/acs.jmedchem.5b01464. Epub 2016 Feb 8.

Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 3CL Protease.

Author information

1
Department of Chemistry, Wichita State University , Wichita, Kansas 67260, United States.
2
Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University , Manhattan, Kansas 66506, United States.
3
LiS Consulting , Lawrence, Kansas 66046, United States.
4
Protein Structure Laboratory, The University of Kansas , Lawrence, Kansas 66047, United States.
5
IMCA-CAT, Hauptman-Woodward Medical Research Institute, APS Argonne National Laboratory, Argonne, Illinois 60439, United States.

Abstract

Human noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. Norovirus 3CL protease plays a vital role in viral replication by generating structural and nonstructural proteins via the cleavage of the viral polyprotein. Thus, molecules that inhibit the viral protease may have potential therapeutic value. We describe herein the structure-based design, synthesis, and in vitro and cell-based evaluation of the first class of oxadiazole-based, permeable macrocyclic inhibitors of norovirus 3CL protease.

PMID:
26823007
PMCID:
PMC5156532
DOI:
10.1021/acs.jmedchem.5b01464
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no competing financial interest.

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