Alternative core development around the tetracyclic indole class of HCV NS5A inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 26, Issue 20, 2016, Pages 5132-5137

  Tong, Ling ^a   Yu, Wensheng ^a   Coburn, Craig A ^a   Meinke, Peter T ^a   Nair, Anilkumar G ^a   Dwyer, Michael P ^a   Chen, Lei ^a   Selyutin, Oleg ^a   Rosenblum, Stuart B ^a   Jiang, Yueheng ^a   Fells, James ^a   Hu, Bin ^b   Zhong, Bin ^b   Soll, Richard M ^b   Liu, Rong ^a   Agrawal, Sony ^a   Xia, Ellen ^a   Zhai, Ying ^a   Kong, Rong ^a   Ingravallo, Paul ^a   Nomeir, Amin ^a   Asante Appiah, Ernest ^a   Kozlowski, Joseph A ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

^b WUXI APPTEC   (China)

Author keywords

DAA; Direct acting antiviral agents; Elbasvir; HCV infection treatment; HCV NS5A inhibitor; MK 8742; Tetracyclic core

Indexed keywords

ELBASVIR; IMIDAZOLE; INDOLE; NONSTRUCTURAL PROTEIN 5A INHIBITOR; PROLINE; ANTIVIRUS AGENT; INDOLE DERIVATIVE; NS-5 PROTEIN, HEPATITIS C VIRUS; VIRAL PROTEIN;

ANTIVIRAL ACTIVITY; ARTICLE; DRUG POTENCY; DRUG STRUCTURE; GENOTYPE; HEPATITIS C; IN VITRO STUDY; MUTANT; REPLICON; VIROLOGY; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; HEPACIVIRUS;

ANTIVIRAL AGENTS; HEPACIVIRUS; INDOLES; VIRAL NONSTRUCTURAL PROTEINS;

EID: 84989172141     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2016.07.057     Document Type: Article

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30. 22 Alignment of compound 14 to MK-8742 was performed using Rapid Overlay of Chemical Structures (ROCS v. 3.2.0.4) software. A single low-energy conformation of MK-8742 was used as the query molecule to align compound 14. Omega software v. 2.5.1.4 (OpenEye Scientific Software, Inc., Santa Fe, NM, USA) was used to generate up to 500 conformations of compound 14 using default parameters. ROCS was then employed to superimpose MK-8742 and compound 14. Results were visualized using PYMOL (v. 1.7).
31. 23 Compounds 15 and 16 were prepared using same method as Scheme 1. The fluoroproline and difluoroproline were prepared accroding to patent procedures WO2012/050848 A1.