Design and synthesis of 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran derivatives as non-nucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase
A novel class of HCV NS5B RNA dependent RNA polymerase inhibitors containing 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran scaffolds were designed and synthesized. Optimization of the alkyl substituent in the pyran ring showed preference for an n-propyl group,...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2006-01, Vol.16 (2), p.457-460 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Gopalsamy, Ariamala Aplasca, Alexis Ciszewski, Gregory Park, Kaapjoo Ellingboe, John W Orlowski, Mark Feld, Boris Howe, Anita Y M |
| description | A novel class of HCV NS5B RNA dependent RNA polymerase inhibitors containing 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran scaffolds were designed and synthesized. Optimization of the alkyl substituent in the pyran ring showed preference for an n-propyl group, while 5,8-disubstitution pattern is preferred for the aromatic region. Analog 19 displayed potent activity with an IC(50) of 50 nM against HCV NS5B enzyme and was selective over a panel of polymerases. |
| doi_str_mv | 10.1016/j.bmcl.2005.08.114 |
| format | Article |
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Optimization of the alkyl substituent in the pyran ring showed preference for an n-propyl group, while 5,8-disubstitution pattern is preferred for the aromatic region. Analog 19 displayed potent activity with an IC(50) of 50 nM against HCV NS5B enzyme and was selective over a panel of polymerases.</description><identifier>ISSN: 0960-894X</identifier><identifier>DOI: 10.1016/j.bmcl.2005.08.114</identifier><identifier>PMID: 16274990</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Benzofurans - chemical synthesis ; Benzofurans - chemistry ; Benzofurans - pharmacology ; Cell Line, Tumor ; Chlorocebus aethiops ; Drug Design ; Drug Evaluation, Preclinical ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Humans ; Molecular Structure ; Pyrans - chemical synthesis ; Pyrans - chemistry ; Pyrans - pharmacology ; RNA-Dependent RNA Polymerase - antagonists & inhibitors ; RNA-Dependent RNA Polymerase - chemistry ; Structure-Activity Relationship ; Vero Cells ; Viral Nonstructural Proteins - antagonists & inhibitors ; Viral Nonstructural Proteins - chemistry</subject><ispartof>Bioorganic & medicinal chemistry letters, 2006-01, Vol.16 (2), p.457-460</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c216t-da958e5459c19ea6a12f10c8dc3ac133b5844897ddcc71419d739d14b9682a283</citedby><cites>FETCH-LOGICAL-c216t-da958e5459c19ea6a12f10c8dc3ac133b5844897ddcc71419d739d14b9682a283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16274990$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gopalsamy, Ariamala</creatorcontrib><creatorcontrib>Aplasca, Alexis</creatorcontrib><creatorcontrib>Ciszewski, Gregory</creatorcontrib><creatorcontrib>Park, Kaapjoo</creatorcontrib><creatorcontrib>Ellingboe, John W</creatorcontrib><creatorcontrib>Orlowski, Mark</creatorcontrib><creatorcontrib>Feld, Boris</creatorcontrib><creatorcontrib>Howe, Anita Y M</creatorcontrib><title>Design and synthesis of 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran derivatives as non-nucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A novel class of HCV NS5B RNA dependent RNA polymerase inhibitors containing 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran scaffolds were designed and synthesized. 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Analog 19 displayed potent activity with an IC(50) of 50 nM against HCV NS5B enzyme and was selective over a panel of polymerases.</description><subject>Animals</subject><subject>Benzofurans - chemical synthesis</subject><subject>Benzofurans - chemistry</subject><subject>Benzofurans - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Chlorocebus aethiops</subject><subject>Drug Design</subject><subject>Drug Evaluation, Preclinical</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Humans</subject><subject>Molecular Structure</subject><subject>Pyrans - chemical synthesis</subject><subject>Pyrans - chemistry</subject><subject>Pyrans - pharmacology</subject><subject>RNA-Dependent RNA Polymerase - antagonists & inhibitors</subject><subject>RNA-Dependent RNA Polymerase - chemistry</subject><subject>Structure-Activity Relationship</subject><subject>Vero Cells</subject><subject>Viral Nonstructural Proteins - antagonists & inhibitors</subject><subject>Viral Nonstructural Proteins - chemistry</subject><issn>0960-894X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1r3DAQhn1oSdKkf6CH4lNPkaOx5Q8d0-3HBkIKSVsKyyJkadzVYkuuZAfcP9e_Vnt3odDTMDPvMww8UfQGaAIUipt9UneqTVJK84RWCQB7EV1QXlBScfbjPHoVwp5SYJSxs-gcirRknNOL6M8HDOanjaXVcZjssJvbELsmzq4Z0WY3ae8IrMkGtqRG-9sNO4PWbdLrjKhtP3l5ZP-LHxZus0zr7YFrxiWq0ZtnOZhnDLEMsXWW2FG16ILRGBu7M7UZnD98sF59jx-e8vfx48PtDPZoNdrh0PWunTr0MuBV9LKRbcDXp3oZffv08etqTe6_fL5b3d4TlUIxEC15XmHOcq6AoywkpA1QVWmVSQVZVucVYxUvtVaqBAZclxnXwGpeVKlMq-wyene823v3a8QwiM4EhW0rLboxiJLCjJf5HEyPQeVdCB4b0XvTST8JoGJRJfZiUSUWVYJWYlY1Q29P18e6Q_0POXnK_gKPDZNO</recordid><startdate>20060115</startdate><enddate>20060115</enddate><creator>Gopalsamy, Ariamala</creator><creator>Aplasca, Alexis</creator><creator>Ciszewski, Gregory</creator><creator>Park, Kaapjoo</creator><creator>Ellingboe, John W</creator><creator>Orlowski, Mark</creator><creator>Feld, Boris</creator><creator>Howe, Anita Y M</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20060115</creationdate><title>Design and synthesis of 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran derivatives as non-nucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase</title><author>Gopalsamy, Ariamala ; 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Optimization of the alkyl substituent in the pyran ring showed preference for an n-propyl group, while 5,8-disubstitution pattern is preferred for the aromatic region. Analog 19 displayed potent activity with an IC(50) of 50 nM against HCV NS5B enzyme and was selective over a panel of polymerases.</abstract><cop>England</cop><pmid>16274990</pmid><doi>10.1016/j.bmcl.2005.08.114</doi><tpages>4</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2006-01, Vol.16 (2), p.457-460 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals Benzofurans - chemical synthesis Benzofurans - chemistry Benzofurans - pharmacology Cell Line, Tumor Chlorocebus aethiops Drug Design Drug Evaluation, Preclinical Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Humans Molecular Structure Pyrans - chemical synthesis Pyrans - chemistry Pyrans - pharmacology RNA-Dependent RNA Polymerase - antagonists & inhibitors RNA-Dependent RNA Polymerase - chemistry Structure-Activity Relationship Vero Cells Viral Nonstructural Proteins - antagonists & inhibitors Viral Nonstructural Proteins - chemistry |
| title | Design and synthesis of 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran derivatives as non-nucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase |
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