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dc.contributor.authorKankanamalage, Anushka C. Galasiti
dc.contributor.authorKim, Yunjeong
dc.contributor.authorRathnayake, Athri D.
dc.contributor.authorAlliston, Kevin R.
dc.contributor.authorButler, Michelle M.
dc.contributor.authorCardinale, Steven C.
dc.contributor.authorBowlin, Terry L.
dc.contributor.authorGroutas, William C.
dc.contributor.authorChang, Kyeong-Ok
dc.date.accessioned2017-08-28T19:36:46Z
dc.date.available2017-08-28T19:36:46Z
dc.date.issued2017-07-03
dc.identifier.citationAnushka C. Galasiti Kankanamalage, Yunjeong Kim, Athri D. Rathnayake, Kevin R. Alliston, Michelle M. Butler, Steven C. Cardinale, Terry L. Bowlin, William C. Groutas, and Kyeong-Ok Chang. Design, Synthesis, and Evaluation of Novel Prodrugs of Transition State Inhibitors of Norovirus 3CL Protease. Journal of Medicinal Chemistry 2017, vol. 60::no. 14:pp 6239-6248en_US
dc.identifier.issn0022-2623
dc.identifier.otherWOS:000406727700019
dc.identifier.urihttp://dx.doi.org/10.1021/acs.jmedchem.7b00497
dc.identifier.urihttp://hdl.handle.net/10057/14054
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractEster and carbamate prodrugs of aldehyde bisulfite adduct inhibitors were synthesized in order to improve their pharmacokinetic and pharmacodynamic properties. The inhibitory activity of the compounds against norovirus 3C-like protease in enzyme and cell-based assays was determined. The ester and carbamate prodrugs displayed equivalent potency to those of the precursor aldehyde bisulfite adducts and precursor aldehydes. Furthermore, the rate of ester cleavage was found to be dependent on alkyl chain length. The generated prodrugs exhibited low cytotoxicity and satisfactory liver microsomes stability and plasma protein binding. The methodology described herein has wide applicability and can be extended to the bisulfite adducts of common warheads employed in:the design of transition state inhibitors of serine and cysteine proteases of medical relevance.en_US
dc.description.sponsorshipNational Institutes of Health (AI109039).en_US
dc.language.isoen_USen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.ispartofseriesJournal of Medicinal Chemistry;v.60:no.14
dc.subjectNorwalk virusen_US
dc.subjectDiscoveryen_US
dc.subjectGastroenteritisen_US
dc.subjectChallengesen_US
dc.subjectProteinasesen_US
dc.subjectAntiviralsen_US
dc.subjectChemistryen_US
dc.subjectInfectionen_US
dc.subjectFoodborneen_US
dc.subjectBiologyen_US
dc.titleDesign, synthesis, and evaluation of novel prodrugs of transition state inhibitors of norovirus 3CL proteaseen_US
dc.typeArticleen_US
dc.rights.holderCopyright © 2017 American Chemical Societyen_US


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