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Improved P2 phenylg...
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Lampa, AnnaUppsala universitet,Avdelningen för organisk farmaceutisk kemi
(author)
Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents
- Article/chapterEnglish2010
Publisher, publication year, extent ...
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Elsevier BV,2010
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-129431
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-129431URI
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https://doi.org/10.1016/j.bmc.2010.05.027DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Phenylglycine has proved to be a useful P2 residue in HCV NS3 protease inhibitors. A novel pi-pi-interaction between the phenylglycine and the catalytic H57 residue of the protease is postulated. We hypothesized that the introduction of a vinyl on the phenylglycine might strengthen this pi-pi-interaction. Thus, herein is presented the synthesis and inhibitory potency of a series of acyclic vinylated phenylglycine-based HCV NS3 protease inhibitors. Surprisingly, inhibitors based on both D- and L-phenylglycine were found to be effective inhibitors, with a slight preference for the d-epimers. Furthermore, prime-side alkenylic extension of the C-terminal acylsulfonamide group gave significantly improved inhibitors with potencies in the nanomolar range (approximately 35 nM), potencies which were retained on mutant variants of the protease.
Subject headings and genre
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HCV
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Protease inhibitors
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Peptidomimetics
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Phenylglycine
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Resistance
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Alkenylic acylsulfonamides
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PHARMACY
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FARMACI
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NATURAL SCIENCES
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NATURVETENSKAP
Added entries (persons, corporate bodies, meetings, titles ...)
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Ehrenberg, Angelica E.Uppsala universitet,Biokemi
(author)
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Gustafsson, Sofia S.Uppsala universitet,Biokemi(Swepub:uu)sofsv946
(author)
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Vema, AparnaUppsala universitet,Avdelningen för organisk farmaceutisk kemi
(author)
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Åkerblom, EvaUppsala universitet,Avdelningen för organisk farmaceutisk kemi(Swepub:uu)eak28141
(author)
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Lindeberg, GunnarUppsala universitet,Avdelningen för organisk farmaceutisk kemi(Swepub:uu)gunnlind
(author)
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Karlén, AndersUppsala universitet,Avdelningen för organisk farmaceutisk kemi(Swepub:uu)anderskl
(author)
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Danielson, U. HelenaUppsala universitet,Biokemi(Swepub:uu)helenads
(author)
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Sandström, AnjaUppsala universitet,Avdelningen för organisk farmaceutisk kemi(Swepub:uu)anjajoha
(author)
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Uppsala universitetAvdelningen för organisk farmaceutisk kemi
(creator_code:org_t)
Related titles
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In:Bioorganic & Medicinal Chemistry: Elsevier BV18:14, s. 5413-54240968-08961464-3391
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