Synthesis and Structure-Activity Relationship Studies of 3-Substituted Indolin-2-ones as Effective Neuroprotective Agents

被引：23

作者：

Balderamos, Michael ^{[1
]}

Ankati, Haribabu ^{[2
]}

Akubathini, Shashidhar Kumar ^{[2
]}

Patel, Anish V. ^{[1
]}

Kamila, Sukanta ^{[2
]}

Mukherjee, Chandrani ^{[2
]}

Wang, Lulu ^{[1
]}

Biehl, Edward R. ^{[2
]}

D'Mello, Santosh R. ^{[1
]}

机构：

[1] Univ Texas Dallas, Dept Mol & Cell Biol, Richardson, TX 75083 USA

[2] So Methodist Univ, Dept Chem, Dallas, TX 75275 USA

来源：

EXPERIMENTAL BIOLOGY AND MEDICINE | 2008年 / 233卷 / 11期

关键词：

neuroprotection; indolone; neurons; neurodegenerative disease;

D O I：

10.3181/0805-RM-153

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Neurodegenerative diseases are a major health problem particularly among the elderly. Drugs to prevent or slow down the death of neurons are urgently needed but are currently unavailable. We previously reported that the c-Raf inhibitor, GW5074 {5-iodo-3-[(3',5'-dibromo-4'-hydroxyphenyl) methylene]-2-indolinone}, is protective in tissue culture and in vivo paradigms of neurodegeneration. However, at doses slightly higher than those at which it is protective, GW5074 displays toxicity when tested in neuronal cultures. We report herein the synthesis, biological evaluation, and structure-activity relationship (SAR) studies of novel 3-substituted indolin-2-one compounds that are highly neuroprotective but lack the toxicity of GW5074. Of the 45 analogs tested in this study, compounds 7, 37, 39, and 45 were found to be the most potent neuroprotective and thus represent promising lead compounds for preclinical development for the treatment of neurodegenerative disorders. Exp Biol Med 233:1395-1402, 2008

引用

页码：1395 / 1402

页数：8

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