Synthesis and biological evaluation of NO-donor-tacrine hybrids as hepatoprotective anti-Alzheimer drug candidates

被引：129

作者：

Fang, Lei ^{[1
,4
]}

Appenroth, Dorothea ^{[2
]}

Decker, Michael ^{[1
,5
]}

Kiehmopf, Michael ^{[3
]}

Roegler, Carolin ^{[1
]}

Deufel, Thomas ^{[3
]}

Fleck, Christian ^{[2
]}

Peng, Sixun ^{[4
]}

Zhang, Yihua ^{[4
]}

Lehmann, Jochen ^{[1
]}

机构：

[1] Univ Jena, Inst Pharm, D-07743 Jena, Germany

[2] Univ Jena, Inst Pharmacol & Toxicol, D-07743 Jena, Germany

[3] Univ Jena, Inst Clin Chem, D-07743 Jena, Germany

[4] China Pharmmaceut Univ, Ctr Drug Discovery, Nanjing 210009, Peoples R China

[5] Harvard Univ, Sch Med, McLean Hosp, Med Chem Program, Belmont, MA 02478 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 04期

关键词：

D O I：

10.1021/jm701491k

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

In search of safer anti-Alzheimer drugs, 14 NO-donor-tacrine hybrids (1-14) were synthesized and evaluated for their ability to inhibit cholinesterases and for vasorelaxation effects. Compounds 1-13 showed good cholinesterases inhibitory activities in vitro, while 14, particularly, was highly selective, preferring butyrylcholinesterase rather than acetylcholinesterase. Four selected compounds (1, 9, 11, and 14) moderately relaxed the porcine pulmonary arteries in organ bath. In the hepatotoxicity study, significant hepatotoxicity was caused by tacrine but not by 9.

引用

页码：713 / 716

页数：4

共 30 条

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HETEROGENEITY OF ADVERSE HEPATIC REACTIONS TO TETRAHYDROAMINOACRIDINE [J].