Design and synthesis of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors.: Part 3:: In vitro evaluation of 1,3,4,5-tetrahydro-benzo[c][1,6] and [c][1,7]-naphthyridin-6-ones

被引：27

作者：

Ferraris, D ^{[1
]}

Ficco, RP ^{[1
]}

Pahutski, T ^{[1
]}

Lautar, S ^{[1
]}

Huang, S ^{[1
]}

Zhang, J ^{[1
]}

Kalish, V ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(03)00465-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The 1,3,4,5-tetrahydro-benzo[c][1,6]- and [c][1,7]-napthyridin-6-ones are presented as a potent class of PARP-1 inhibitors. Derivatives of these partially saturated aza-5[H]-phenanthridin-6-ones were designed and synthesized with tertiary amines for salt formation. thus enhancing aqueous solubility, iv formulation and their potential use in acute ischemic injuries (i.e., myocardial ischemia and stroke). We found that partial saturation of the C-ring results in derivatives that are several times more potent than the aromatic C-ring derivatives. The general synthetic routes are presented herein as well as thorough in vitro potencies and SAR discussion for selected derivatives. (C) 2003 Elsevier Ltd. All rights reserved.

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收藏

页码：2513 / 2518

页数：6

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