3lkh

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[[Image:3lkh.png|left|200px]]
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==Inhibitors of Hepatitis C Virus Polymerase: Synthesis and Characterization of Novel 6-Fluoro-N-[2-Hydroxy-1(S)-Benzamides==
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<StructureSection load='3lkh' size='340' side='right' caption='[[3lkh]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3lkh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LKH FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LT6:2-(2-{[(1S)-1-BENZYL-2-HYDROXYETHYL]AMINO}-2-OXOETHOXY)-N-BUTYL-6-FLUORO-N-METHYLBENZAMIDE'>LT6</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NS5B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 Hepatitis C virus])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lkh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lkh RCSB], [http://www.ebi.ac.uk/pdbsum/3lkh PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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SAR exploration from an initial hit, (S)-N-(2-cyclohexenylethyl)-2-fluoro-6-(2-(1-hydroxy-3-phenylpropan-2-ylam ino)-2-oxoethoxy)benzamide (1), identified using our proprietary automated ligand identification system (ALIS),(1) has led to a novel series of selective hepatitis C virus (HCV) NS5B polymerase inhibitors with improved in vitro potency as exemplified by (S)-2-fluoro-6-(2-(1-hydroxy-3-phenylpropan-2-ylamino)-2-oxoethoxy)-N-isop entyl-N-methylbenzamidecarboxamide (41) (IC(50)=0.5 microM). The crystal structure of an analogue (44) was solved and provided rationalization of the SAR of this series, which binds in a distinct manner in the palm domain of NS5B, consistent with biochemical analysis using enzyme mutant variants. These data warrant further lead optimization efforts on this novel series of non-nucleoside inhibitors targeting the HCV polymerase.
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{{STRUCTURE_3lkh| PDB=3lkh | SCENE= }}
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Inhibitors of hepatitis C virus polymerase: synthesis and characterization of novel 2-oxy-6-fluoro-N-((S)-1-hydroxy-3-phenylpropan-2-yl)-benzamides.,Cheng CC, Shipps GW Jr, Yang Z, Kawahata N, Lesburg CA, Duca JS, Bandouveres J, Bracken JD, Jiang CK, Agrawal S, Ferrari E, Huang HC Bioorg Med Chem Lett. 2010 Apr 1;20(7):2119-24. Epub 2010 Feb 18. PMID:20219368<ref>PMID:20219368</ref>
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===Inhibitors of Hepatitis C Virus Polymerase: Synthesis and Characterization of Novel 6-Fluoro-N-[2-Hydroxy-1(S)-Benzamides===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_20219368}}
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==About this Structure==
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[[3lkh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LKH OCA].
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==See Also==
==See Also==
*[[RNA polymerase|RNA polymerase]]
*[[RNA polymerase|RNA polymerase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020219368</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Hepatitis c virus]]
[[Category: Hepatitis c virus]]
[[Category: RNA-directed RNA polymerase]]
[[Category: RNA-directed RNA polymerase]]
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[[Category: Lesburg, C A.]]
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[[Category: Lesburg, C A]]
[[Category: Apoptosis]]
[[Category: Apoptosis]]
[[Category: Atp-binding]]
[[Category: Atp-binding]]

Revision as of 08:39, 9 December 2014

Inhibitors of Hepatitis C Virus Polymerase: Synthesis and Characterization of Novel 6-Fluoro-N-[2-Hydroxy-1(S)-Benzamides

3lkh, resolution 2.05Å

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