Rational approaches to discovery of orally active and brain-penetrable quinazolinone inhibitors of poly(ADP-ribose)polymerase

被引：85

作者：

Hattori, K

Kido, Y

Yamamoto, H

Ishida, J

Kamijo, K

Murano, K

Ohkubo, M

Kinoshita, T

Iwashita, A

Mihara, K

Yamazaki, S

Matsuoka, N

Teramura, Y

Miyake, H

机构：

[1] Fujisawa Pharmaceut Co Ltd, Med Chem Res Labs, Yodogawa Ku, Osaka 5328514, Japan

[2] Fujisawa Pharmaceut Co Ltd, Exploratory Res Labs, Yodogawa Ku, Osaka 5328514, Japan

[3] Fujisawa Pharmaceut Co Ltd, Med Biol Res Labs, Yodogawa Ku, Osaka 5328514, Japan

[4] Fujisawa Pharmaceut Co Ltd, Biopharmaceut & Pharmacokinet Res Labs, Yodogawa Ku, Osaka 5328514, Japan

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 17期

关键词：

D O I：

10.1021/jm0499256

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of quinazolinone derivatives as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors has been discovered. Key to success was application of a rational discovery strategy involving structure-based design, combinatorial chemistry, and classical SAR for improvement of potency and bioavailability. The new inhibitors were shown to bind to the nicotinamide-ribose binding site (NI site) and the adenosine-ribose binding site (AD site) of NAD(+).

引用

页码：4151 / 4154

页数：4

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