3lkh | pdb_00003lkh

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

spinqualitylabelsall models 3lkh, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3lkh is a 2 chain structure with sequence from Hepatitis c virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: LT6 Gene: NS5B (Hepatitis C virus) Activity: RNA-directed RNA polymerase, with EC number 2.7.7.48 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase

Proteopedia Page Contributors and Editors (what is this?)

OCA