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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. 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.

SUBMITTER: Damalanka VC

PROVIDER: S-EPMC5296247 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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

Damalanka Vishnu C VC Kim Yunjeong Y Galasiti Kankanamalage Anushka C AC Lushington Gerald H GH Mehzabeen Nurjahan N Battaile Kevin P KP Lovell Scott S Chang Kyeong-Ok KO Groutas William C WC

European journal of medicinal chemistry 20161221

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 ...[more]

PMID: 28038326

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