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

被引：102

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.

引用

页码：6950 / 6953

页数：4

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