Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives

被引：91

作者：

Secci, Daniela ^{[1
]}

Carradori, Simone ^{[1
]}

Bolasco, Adriana ^{[1
]}

Chimenti, Paola ^{[1
]}

Yanez, Matilde

Ortuso, Francesco ^{[2
]}

Alcaro, Stefano ^{[2
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, I-00185 Rome, Italy

[2] Univ Catanzaro Magna Graecia, Dipartimento Sci Farmacobiol, I-88021 Roccelletta Di Borgia, CZ, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 10期

关键词：

Monoamine oxidase; Coumarin; Hydrazido; Hydrolytic stability; STEREOSELECTIVE RECOGNITION MECHANISMS; 7-SUBSTITUTED COUMARINS; PREDICTION;

D O I：

10.1016/j.ejmech.2011.07.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several 3-carbonyl (1-26), 3-acyl (27-52), and 3-carboxyhydrazido (53-58) coumarins have been synthesized in high yields (72-99%) and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Different substituents on the coumarin nucleus were evaluated for their effect on biological activity and isoform selectivity. Substitution at position C7 of the 3-ethyl ester coumarin ring, or the introduction of a hydrazido substituent at C3, were important to obtain highly potent and selective hMAO-B inhibitors with IC50 values in the nanomolar range. Some derivatives were also submitted to a stability test and showed no chemical cleavage in vitro. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：4846 / 4852

页数：7

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