Lead optimization of 2-hydroxymethyl imidazoles as non-hydroxamate LpxC inhibitors: Discovery of TP0586532.
Bioorg Med Chem
; 30: 115964, 2021 01 15.
Article
em En
| MEDLINE
| ID: mdl-33385955
ABSTRACT
Infectious diseases caused by resistant Gram-negative bacteria have become a serious problem, and the development of therapeutic drugs with a novel mechanism of action and that do not exhibit cross-resistance with existing drugs has been earnestly desired. UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is a drug target that has been studied for a long time. However, no LpxC inhibitors are available on the market at present. In this study, we sought to create a new antibacterial agent without a hydroxamate moiety, which is a common component of the major LpxC inhibitors that have been reported to date and that may cause toxicity. As a result, a development candidate, TP0586532, was created that is effective against carbapenem-resistant Klebsiella pneumoniae and does not pose a cardiovascular risk.
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Base de dados:
MEDLINE
Assunto principal:
Inibidores Enzimáticos
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Escherichia coli
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Descoberta de Drogas
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Amidoidrolases
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Imidazóis
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Klebsiella pneumoniae
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Antibacterianos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article