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SAR研究促成了一系列新型金属β-内酰胺酶抑制剂的鉴定，这些抑制剂用于治疗对碳青霉烯类耐药的肠杆菌科细菌感染，且在动物感染模型中显示出疗效。

SAR Studies Leading to the Identification of a Novel Series of Metallo-β-lactamase Inhibitors for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy in an Animal Infection Model.

作者信息

Leiris Simon, Coelho Alicia, Castandet Jérôme, Bayet Maëlle, Lozano Clarisse, Bougnon Juliette, Bousquet Justine, Everett Martin, Lemonnier Marc, Sprynski Nicolas, Zalacain Magdalena, Pallin Thomas David, Cramp Michael C, Jennings Neil, Raphy Gilles, Jones Mark W, Pattipati Ramesh, Shankar Battu, Sivasubrahmanyam Relangi, Soodhagani Ashok K, Juventhala Ramakrishna R, Pottabathini Narender, Pothukanuri Srinivasu, Benvenuti Manuela, Pozzi Cecilia, Mangani Stefano, De Luca Filomena, Cerboni Giulia, Docquier Jean-Denis, Davies David T

机构信息

Antabio SAS , 436 rue Pierre et Marie Curie , 31670 Labège , France.

Zala Drug Discovery Consulting LLC , West Chester , Pennsylvania 19380 , United States.

出版信息

ACS Infect Dis. 2019 Jan 11;5(1):131-140. doi: 10.1021/acsinfecdis.8b00246. Epub 2018 Nov 30.

DOI:10.1021/acsinfecdis.8b00246
PMID:30427656
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6332448/
Abstract

The clinical effectiveness of carbapenem antibiotics such as meropenem is becoming increasingly compromised by the spread of both metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) enzymes on mobile genetic elements, stimulating research to find new β-lactamase inhibitors to be used in conjunction with carbapenems and other β-lactam antibiotics. Herein, we describe our initial exploration of a novel chemical series of metallo-β-lactamase inhibitors, from concept to efficacy, in a survival model using an advanced tool compound (ANT431) in conjunction with meropenem.

摘要

美罗培南等碳青霉烯类抗生素的临床有效性正日益受到金属β-内酰胺酶（MBL）和丝氨酸β-内酰胺酶（SBL）在移动遗传元件上传播的影响，这促使人们开展研究以寻找新的β-内酰胺酶抑制剂，用于与碳青霉烯类及其他β-内酰胺类抗生素联合使用。在此，我们描述了从概念到疗效，在使用先进工具化合物（ANT431）与美罗培南联合的生存模型中，对新型金属β-内酰胺酶抑制剂化学系列的初步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da0b/6332448/0f69d048eef4/id-2018-002469_0006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da0b/6332448/0f69d048eef4/id-2018-002469_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da0b/6332448/5070b19a66ff/id-2018-002469_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da0b/6332448/0d630746fa8c/id-2018-002469_0001.jpg
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