Discovery of Conformationally Constrained Tetracyclic Compounds as Potent Hepatitis C Virus NS5B RNA Polymerase Inhibitors
Journal of Medicinal Chemistry2006Vol. 49(24), pp. 6950–6953
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Kazutaka Ikegashira, Takahiro Oka, Shintaro Hirashima, Satoru Noji, Hiroshi Yamanaka, Yoshinori Hara, Tsuyoshi Adachi, Jun-Ichiro Tsuruha, Satoki Doi, Yasunori Hase, Tōru Noguchi, Izuru Ando, Naoki Ogura, Satoru Ikeda, Hiromasa Hashimoto
Abstract
We report a new series of hepatitis C virus NS5B RNA polymerase inhibitors containing a conformationally constrained tetracyclic scaffold. SAR studies led to the identification of 6,7-dihydro-5H-benzo[5,6][1,4]diazepino[7,1-a]indoles (19 and 20) bearing a basic pendent group with high biochemical and cellular potencies. These compounds displayed a very small shift in cellular potency when the replicon assay was performed in the presence of human serum albumin.
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