3UPH

Synthesis of novel 4,5-dihydrofurano indoles and their evaluation as HCV NS5B polymerase inhibitors


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Synthesis of New 4,5-Dihydrofuranoindoles and Their Evaluation as HCV NS5B Polymerase Inhibitors.

Velazquez, F.Venkatraman, S.Lesburg, C.A.Duca, J.Rosenblum, S.B.Kozlowski, J.A.Njoroge, F.G.

(2012) Org Lett 14: 556-559

  • DOI: https://doi.org/10.1021/ol203177g
  • Primary Citation of Related Structures:  
    3UPH, 3UPI

  • PubMed Abstract: 

    The synthesis of substituted 3,4-dihydrofuranoindoles is reported. These new indole compounds were used to synthesize potent HCV NS5B inhibitors. The binding mode of the dihydrofuranoindole-derived inhibitors was established via X-ray crystallographic studies.


  • Organizational Affiliation

    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033-1300, USA. francisco.velazquez@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase
A, B
576Hepatitis C virus isolate HC-J4Mutation(s): 0 
EC: 2.7.7.48
UniProt
Find proteins for O92972 (Hepatitis C virus genotype 1b (strain HC-J4))
Explore O92972 
Go to UniProtKB:  O92972
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO92972
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0C1
Query on 0C1

Download Ideal Coordinates CCD File 
D [auth A],
E [auth B]
6-(2,5-difluorobenzyl)-N-(methylsulfonyl)-8-(2-oxo-1,2-dihydropyridin-3-yl)-3,6-dihydro-2H-furo[2,3-e]indole-7-carboxamide
C24 H19 F2 N3 O5 S
GPKCKCQUVBOYCV-UHFFFAOYSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
C [auth A]PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
Binding Affinity Annotations 
IDSourceBinding Affinity
0C1 Binding MOAD:  3UPH IC50: 15 (nM) from 1 assay(s)
PDBBind:  3UPH IC50: 15 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.97α = 90
b = 106.328β = 90
c = 134.297γ = 90
Software Package:
Software NamePurpose
JDirectordata collection
BUSTERrefinement
DENZOdata reduction
SCALEPACKdata scaling
BUSTERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-01-25
    Type: Initial release
  • Version 1.1: 2012-02-01
    Changes: Database references