3UPI

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

Summary for 3UPI

• Entry DOI: 10.2210/pdb3upi/pdb
• Related: 3UPH
• Descriptor: RNA-directed RNA polymerase, PHOSPHATE ION, (3S)-6-(2,5-difluorobenzyl)-3-methyl-N-(methylsulfonyl)-8-(2-oxo-1,2-dihydropyridin-3-yl)-3,6-dihydro-2H-furo[2,3-e]indole-7-carboxamide, ... (4 entities in total)
• Functional Keywords: transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Hepatitis C virus (HCV)
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein (By similarity). Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): O92972
• Total number of polymer chains: 2
• Total formula weight: 131761.61

Authors

Velazquez, F.,Venkataraman, S.,Lesburg, C.A.,Duca, J.S.,Rosenblum, S.B.,Kozlowski, J.A.,Njoroge, F.G. (deposition date: 2011-11-18, release date: 2012-01-25, Last modification date: 2012-02-01)

Primary citation

Velazquez, F.,Venkatraman, S.,Lesburg, C.A.,Duca, J.,Rosenblum, S.B.,Kozlowski, J.A.,Njoroge, F.G.
Synthesis of New 4,5-Dihydrofuranoindoles and Their Evaluation as HCV NS5B Polymerase Inhibitors.
Org.Lett., 14:556-559, 2012

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.

PubMed: 22220815
DOI: 10.1021/ol203177g

Experimental method

X-RAY DIFFRACTION (2 Å)