On August 14, 2014, Dai, Xing; Liu, Hong; Palani, Anandan; He, Shuwen; Lai, Zhong; Nargund, Ravi; Marcantonio, Karen; Xiao, Dong; Brockunier, Linda L.; Zorn, Nicolas; Dang, Qun; Peng, Xuanjia; Li, Peng published a patent.Electric Literature of 1256359-96-2 The title of the patent was Preparation of tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis C. And the patent contained the following:
The invention relates to compounds of formula I that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system. Compounds of formula I wherein A is C3-6 cycloalkyl, azetidin-1-ylcarbonyl and 5- to 6-membered aromatic ring system optionally containing heteroatoms; ring B is benzofuran, pyridinofuran pyrazolopyridine, etc.; Z1, Z2 and Z3 are independently CH and H, with the proviso that no more than one of Z1 – Z3 is N; Z4 is N, Z5 is CH and dashed bond to Z5 is double bond; Z4 is C, Z5 is NH and dashed bond is to Z5 is single bond; R2 is H, C1-6 alkyl, and C1-6 alkoxy; R3 is H and C1-6 alkyl; R4 is C1-6 alkyl and C1-6 alkoxy; R5 is H, C1-6 alkyl, CH2CO2H and derivatives, and SO2Me; R6 is H, C1-6 alkyl, C1-6 haloalkyl, etc.; R7 is H and C1-6 alkyl; R6R7 taken together to form C3-4 cycloalkyl; R8 is H, halo and CN; R9 and R10 are independently H and halo; dashed bond is single and double bond; and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by a multistep procedure (procedure given). The invention compounds were evaluated for their anti-HCV activity. From the assay, it was determined that compound II exhibited IC50 values in the range of 4.006 nM to 6.558 nM. The experimental process involved the reaction of 4-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole(cas: 1256359-96-2).Electric Literature of 1256359-96-2
The Article related to tetracyclic heterocycle preparation antiviral treatment hepatitis c, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Electric Literature of 1256359-96-2
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles