Synthesis of substituted 5[H]phenanthridin-6-ones as potent poly(ADP-ribose)polymerase-1 (PARP1) inhibitors

被引：54

作者：

Li, JH ^{[1
]}

Serdyuk, L ^{[1
]}

Ferraris, DV ^{[1
]}

Xiao, G ^{[1
]}

Tays, KL ^{[1
]}

Kletzly, PW ^{[1
]}

Li, WX ^{[1
]}

Lautar, S ^{[1
]}

Zhang, J ^{[1
]}

Kalish, VJ ^{[1
]}

机构：

[1] Guilford Pharmaceut Inc, Baltimore, MD 21224 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 13期

关键词：

D O I：

10.1016/S0960-894X(01)00281-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

1-, 2-, 3-, 4-, 8-, or 10-Substituted 5(H)phenanthridin-6-ones were synthesized and found to be potent PARP1 inhibitors. Among the 28 compounds prepared. some showed not only low IC50 values (compound 1b, 10 nM) but also desirable water solubility characteristics. These properties, which are superior to the common PARP1 inhibitors such as benzamides and isoquinolin-1-ones, are essential for potential therapeutic usage. The variety of compounds allows SAR analysis of favored substituents and substituted positions on 5(H)phenanthridin-6-one ring. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：1687 / 1690

页数：4