Design and synthesis of 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran derivatives as non-nucleoside inhibitors of HCVNS5B RNA dependent RNA polymerase

被引：42

作者：

Gopalsamy, A ^{[1
]}

Aplasca, A

Ciszewski, G

Park, K

Ellingboe, JW

Orlowski, M

Feld, B

Howe, AYM

机构：

[1] Wyeth Ayerst Res, Chem & Screening Sci, Pearl River, NY 10965 USA

[2] Wyeth Ayerst Res, Infect Dis, Pearl River, NY 10965 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 02期

关键词：

HCV polymerase inhibitors; 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran; 3,4-dihydro-1H-pyrano[3,4-b]benzofuran;

D O I：

10.1016/j.bmcl.2005.08.114

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of HCV NS513 RNA dependent RNA polymerase inhibitors containing 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran scaffolds were designed and synthesized. Optimization of the alkyl substituent in the pyran ring showed preference for an n-propyl group, while 5,8-disubstitution pattern is preferred for the aromatic region. Analog 19 displayed potent activity with an IC50 of 50 nM against HCV NS513 enzyme and was selective over a panel of polymerases. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：457 / 460

页数：4

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