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单胺氧化酶抑制剂及其更广泛应用:专利综述

MAO inhibitors and their wider applications: a patent review.

作者信息

Carradori Simone, Secci Daniela, Petzer Jacques P

机构信息

a Department of Pharmacy , "G. d'Annunzio" University of Chieti-Pescara , Chieti , Italy.

b Dipartimento di Chimica e Tecnologie del Farmaco , Sapienza University of Rome , Rome , Italy.

出版信息

Expert Opin Ther Pat. 2018 Mar;28(3):211-226. doi: 10.1080/13543776.2018.1427735. Epub 2018 Jan 17.

Abstract

INTRODUCTION

Monoamine oxidase (MAO) inhibitors, after the initial 'golden age', are currently used as third-line antidepressants (selective MAO-A inhibitors) or clinically enrolled as co-adjuvants for neurodegenerative diseases (selective MAO-B inhibitors). However, the research within this field is always increasing due to their pivotal role in modulating synaptic functions and monoamines metabolism.

AREAS COVERED

In this paper, MAO inhibitors (2015-2017) are disclosed ordering all the patents according to their chemical scaffold. Structure-activity relationships (SARs) are extrapolated for the most investigated chemotypes (coumarins, pyrazole/oxazepinones, (hetero)arylamides). 108 Compounds are divided into two main groups: newly synthesized molecules and naturally-occurring metabolites. Finally, new therapeutic options are outlined to ensure a more complete view on the potential of these inhibitors.

EXPERT OPINION

New proposed MAO inhibitors are endowed with a marked isoform selectivity, with innovative therapeutic potential toward other targets (gliomas, inflammation, muscle dystrophies, migraine, chronic pain, pseudobulbar affect), and with a promising ability to address multi-faceted pathologies such as Alzheimer's disease. The increasing number of patents is analyzed collecting data from 2002 to 2017.

摘要

引言

单胺氧化酶(MAO)抑制剂在经历了最初的“黄金时代”后,目前被用作三线抗抑郁药(选择性MAO - A抑制剂),或在临床上作为神经退行性疾病的辅助药物(选择性MAO - B抑制剂)。然而,由于它们在调节突触功能和单胺代谢中起关键作用,该领域的研究一直在增加。

涵盖领域

本文公开了2015 - 2017年的MAO抑制剂,并根据其化学骨架对所有专利进行排序。对研究最多的化学类型(香豆素、吡唑/恶唑酮、(杂)芳基酰胺)推断其构效关系(SARs)。108种化合物分为两大类:新合成分子和天然存在的代谢物。最后,概述了新的治疗选择,以更全面地了解这些抑制剂的潜力。

专家意见

新提出的MAO抑制剂具有显著的同工型选择性,对其他靶点(神经胶质瘤、炎症、肌肉萎缩症、偏头痛、慢性疼痛、假性延髓情绪)具有创新的治疗潜力,并且有能力治疗如阿尔茨海默病等多方面的病症。通过收集2002年至2017年的数据对不断增加的专利数量进行了分析。

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