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2018-2019 年金属β-内酰胺酶抑制剂专利回顾。

A 2018-2019 patent review of metallo beta-lactamase inhibitors.

机构信息

Catalysis and Peptide Research Unit, Westville Campus, University of KwaZulu-Natal , Durban, South Africa.

Science for Life Laboratory, Karolinska Institutet , Stockhlom, Sweden.

出版信息

Expert Opin Ther Pat. 2020 Jul;30(7):541-555. doi: 10.1080/13543776.2020.1767070. Epub 2020 May 20.

Abstract

INTRODUCTION

Antibiotic resistance caused by beta-lactamase expressing bacteria poses a concern given its global dissemination and proliferation. The emergence of the metallo beta-lactamases is an indefinite health threat toward which current antibiotics have limited clinical efficacy. One solution is to develop metallo beta-lactamase inhibitors (MBLIs) capable of restoring the activity of beta-lactam drugs.

AREAS COVERED

This review focuses on potential metallo beta-lactamase inhibitors that have been patented during the period of 2018-2019. The aim is to provide insight into the diverse class of compounds which exhibit a synergistic inhibitory effect on carbapenem-resistant bacteria, when co-administered with a beta-lactam antibiotic.

EXPERT OPINION

The treatment strategy, of creating a broad-spectrum beta-lactamase inhibitor, is beneficial to the health sector as well as rural communities. Unfortunately, most of the inhibitors lack published data from both and evaluation, thus preventing an expert opinion on the likelihood to progress as candidates for clinical trials. From this report, the bismuth complexes, pyridinyl-nicotinamide derived sugars, boronic acid, and thiazole sulfonamide derivatives, portray promising properties for further advancement. Since there is currently no FDA approved MBLI, there remains an urgent need for the development of these combination treatment strategies.

摘要

简介

由于β-内酰胺酶表达细菌引起的抗生素耐药性具有全球传播和增殖的特性,因此引起了人们的关注。金属β-内酰胺酶的出现对健康构成了不确定的威胁,而目前的抗生素对其临床疗效有限。一种解决方案是开发能够恢复β-内酰胺类药物活性的金属β-内酰胺酶抑制剂(MBLIs)。

涵盖领域

本综述重点介绍了 2018 年至 2019 年期间获得专利的潜在金属β-内酰胺酶抑制剂。目的是提供对具有协同抑制作用的化合物的深入了解,当与β-内酰胺类抗生素联合使用时,这些化合物对碳青霉烯类耐药菌具有抑制作用。

专家意见

创建广谱β-内酰胺酶抑制剂的治疗策略对卫生部门和农村社区都有益。不幸的是,大多数抑制剂都缺乏来自和评估的已发表数据,因此无法就其作为临床试验候选药物的进展可能性发表专家意见。从本报告中可以看出,铋配合物、吡啶基烟酸衍生糖、硼酸和噻唑磺酰胺衍生物具有进一步发展的有前景的特性。由于目前没有 FDA 批准的 MBLI,因此仍然迫切需要开发这些联合治疗策略。

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