Discovery of conformationally constrained tetracyclic compounds as potent hepatitis C virus NS5B RNA polymerase inhibitors

Journal of Medicinal Chemistry

Volumn 49, Issue 24, 2006, Pages 6950-6953

  Ikegashira, Kazutaka ^a   Oka, Takahiro ^a   Hirashima, Shintaro ^a   Noji, Satoru ^a   Yamanaka, Hiroshi ^a   Hara, Yoshinori ^a   Adachi, Tsuyoshi ^a   Tsuruha, Jun Ichiro ^a   Doi, Satoki ^a   Hase, Yasunori ^a   Noguchi, Toru ^a   Ando, Izuru ^a   Ogura, Naoki ^a   Ikeda, Satoru ^a   Hashimoto, Hiromasa ^a  

^a JAPAN TOBACCO INC   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

6,7 DIHYDRO 5H BENZO[5,6][1,4]DIAZEPINO[7,1A]INDOLE DERIVATIVE; ENZYME INHIBITOR; INDOLE DERIVATIVE; NUCLEOSIDE ANALOG; PEGINTERFERON ALPHA2B; R 1626; RIBAVIRIN; VALOPICITABINE; VIRUS RNA;

ARTICLE; DRUG CONFORMATION; DRUG DESIGN; DRUG POTENCY; ENZYME INHIBITION; HEPATITIS C; HEPATITIS C VIRUS; HEPATITIS C VIRUS NS5B; HUMAN; IC 50; NONHUMAN; REPLICON; UNSPECIFIED SIDE EFFECT; VIRUS INHIBITION; VIRUS TYPING;

ANTIVIRAL AGENTS; BENZODIAZEPINES; CRYSTALLOGRAPHY, X-RAY; HEPACIVIRUS; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; INDOLES; MODELS, MOLECULAR; MOLECULAR CONFORMATION; REPLICON; RNA, VIRAL; SERUM ALBUMIN; STRUCTURE-ACTIVITY RELATIONSHIP; VIRAL NONSTRUCTURAL PROTEINS;

EID: 33845356771     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0610245     Document Type: Article

References (28)

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21. The random conformational searches were performed with SYBYL 6.9.1 (Tripos Inc., 1669 S. Hanley Road, St. Louis, MO). Details were described in the supporting information.
22. The cocrystal structure coordinate has been deposited in the Protein Data Bank (PDB code 2DXS). For details, see the Supporting Information. The molecular image was generated with PyMOL (PyMOL Molecular Graphics System; DeLano Scientific: San Carlos, CA).
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25. A similar observation has been reported in the indole series. See ref 5.
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