Design of novel nicotinamides as potent and selective monoamine oxidase a inhibitors

被引：18

作者：

Shi, Lei ^{[1
]}

Yang, Ying ^{[1
]}

Li, Zi-Lin ^{[1
]}

Zhu, Zhen-Wei ^{[1
]}

Liu, Chang-Hong ^{[1
]}

Zhu, Hai-Liang ^{[1
]}

机构：

[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 04期

基金：

美国国家科学基金会;

关键词：

Monoamine oxidase; Inhibitors; Nicotinamides; Structure-activity relationship; Molecular docking; CRYSTAL-STRUCTURES; DRUG TARGET; MAO-B; BRAIN; ANTIDEPRESSANTS; POPULATIONS; DISEASE; BINDING;

D O I：

10.1016/j.bmc.2009.12.065

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of N-(2-morpholinoethyl)nicotinamide (1-13) and N-(3-morpholinopropyl)nicotinamide derivatives (14-26) have been designed, synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. Most of these synthesized compounds proved to be potent, and selective inhibitors of MAO-A rather than of MAO-B. 5-Chloro-6-hydroxy-N-(2-morpholinoethyl)nicotinamide (13) displayed the highest MAO-A inhibitory potency (IC50 = 0.045 mu M) and a good selectivity. 2-Bromo-N-(2-morpholinoethyl)nicotinamide (3) was the most potent MAO-B inhibitor with the IC50 value of 0.32 mu M, but it was not selective. Molecular dockings of compound 13 were performed in order to give structural insights regarding the MAO-A selectivity. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1659 / 1664

页数：6

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