Rational design of conformationally restricted quinazolinone inhibitors of poly(ADP-ribose)polymerase

被引：35

作者：

Hattori, Kouji

Kido, Yoshiyuki

Yamamoto, Hirofurm

Ishida, Junya

Iwashita, Akinori

Mihara, Kayoko

机构：

[1] Astellas Pharma Inc, Chem Res Labs, Tsukuba, Ibaraki 3058585, Japan

[2] Astellas Pharma Inc, Pharmaceut Res Labs, Tsukuba, Ibaraki 3058585, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 20期

关键词：

Poly(ADP-ribose)polymerase PARP-1; SBDD; x-ray; quinazolinone; conformationally restricted;

D O I：

10.1016/j.bmcl.2007.07.091

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

A successful design of conformationally restricted novel quinazolinone derivatives linked via a cyclopentene moiety as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors has been developed. One selected member of the new series, 8-chloro-2-[(3 S)-3-(4-phenylpiperidin-1-yl)cyclopent-1-en-1-yl] quinazolin-4(3H)-one (S-16d), was found to be highly potent with IC50 = 8.7 nM and good brain penetration. (c) 2007 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5577 / 5581

页数：5

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