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

被引：101
作者：
Ikegashira, Kazutaka
Oka, Takahiro
Hirashima, Shintaro
Noji, Satoru
Yamanaka, Hiroshi
Hara, Yoshinori
Adachi, Tsuyoshi
Tsuruha, Jun-Ichiro
Doi, Satoki
Hase, Yasunori
Noguchi, Toru
Ando, Izuru
Ogura, Naoki
Ikeda, Satoru
Hashimoto, Hiromasa
机构：
[1] Japan Tobacco Inc, Cent Pharmaceut Res Inst, Takatsuki, Osaka 5091125, Japan
[2] Japan Tobacco Inc, Pharmaceut Frontier Res Labs, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 24期
关键词：
D O I：
10.1021/jm0610245
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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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页码：6950 / 6953
页数：4
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