Synthesis of new 4,5-dihydrofuranoindoles and their evaluation as HCV NS5B polymerase inhibitors.

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.

[1]  D. Knittel,et al.  Enazide, 3. Mitt.: Thermolyse von α-Azidozimtestern; Synthese von Indolderivaten , 1970 .

[2]  M. Plotkin,et al.  A practical approach to highly functionalized benzodihydrofurans , 2000 .

[3]  M. Hamann,et al.  Indole alkaloid marine natural products: An established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases , 2005, Life Sciences.

[4]  Wael A Sakr,et al.  Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy. , 2010, Current drug targets.

[5]  E. Barreiro,et al.  From nature to drug discovery: the indole scaffold as a 'privileged structure'. , 2009, Mini reviews in medicinal chemistry.

[6]  C. Bradsher,et al.  Oxygen heterocycles by the Parham cyclialkylation , 1981 .

[7]  C. Lartigue,et al.  Synthesis and antiviral activity of an imidazo[1,2-a]pyrrolo[2,3-c]pyridine series against the bovine viral diarrhea virus. , 2010, European journal of medicinal chemistry.

[8]  D. Knittel,et al.  Thermolysereaktionen von enazidocarbonylverbindungen , 1970 .

[9]  C. Moody,et al.  Formation of indoles, isoquinolines, and other fused pyridines from azidoacrylates , 1984 .

[10]  H. Huang,et al.  Hepatitis C Virus NS5B Polymerase Exhibits Distinct Nucleotide Requirements for Initiation and Elongation* , 2008, Journal of Biological Chemistry.

[11]  Charles A. Lesburg,et al.  Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site , 1999, Nature Structural Biology.

[12]  B. Stokes,et al.  Intramolecular C-H amination reactions: exploitation of the Rh(2)(II)-catalyzed decomposition of azidoacrylates. , 2007, Journal of the American Chemical Society.

[13]  M. Hamann,et al.  Marine indole alkaloids: potential new drug leads for the control of depression and anxiety. , 2010, Chemical reviews.

[14]  B. Feld,et al.  I. Novel HCV NS5B polymerase inhibitors: discovery of indole 2-carboxylic acids with C3-heterocycles. , 2011, Bioorganic & medicinal chemistry letters.