The discovery and development of selective 3-fluoro-4-aryloxyallylamine inhibitors of the amine oxidase activity of semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1)

被引：33

作者：

Foot, Jonathan S. ^{[1
]}

Deodhar, Mandar ^{[1
]}

Turner, Craig I. ^{[1
]}

Yin, Ping ^{[1
]}

van Dam, Ellen M. ^{[1
]}

Silva, Diego G. ^{[1
]}

Olivieri, Aldo ^{[2
]}

Holt, Andrew ^{[2
]}

McDonald, Ian A. ^{[1
]}

机构：

[1] Pharmaxis Ltd, Frenchs Forest, NSW 2086, Australia

[2] Univ Alberta, Dept Pharmacol, Edmonton, AB T6G 2H7, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 12期

关键词：

SSAO; VAP-1; Allylamines; Amine oxidase; HUMAN UMBILICAL ARTERY; INFLAMMATION; SERUM; DEAMINATION; DISEASES; BINDING; FORM;

D O I：

10.1016/j.bmcl.2012.04.111

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of 3-fluoroallyl amine-based SSAO/VAP-1 inhibitors is reported. These compounds have excellent selectivity over diamine oxidase, MAO-A and MAO-B. Synthesis and SAR studies leading to compound 28 (PXS-4159A) are reported. The pharmacokinetic profile of 28 in the rat, together with activity in a murine model of lung inflammation are also disclosed. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：3935 / 3940

页数：6

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