Discovery and preclinical evaluations of JBD0131, a novel nitrodihydro-imidazooxazole anti-tuberculosis agent.
Bioorg Med Chem Lett
; 72: 128871, 2022 09 15.
Article
em En
| MEDLINE
| ID: mdl-35777718
ABSTRACT
Multidrug-resistant pulmonary tuberculosis (MDR-TB) is a major health problem worldwide. The treatment for MDR-TB requires medications for a long duration (up to 20-24 months) with second-line drugs resulting in unfavorable outcomes. Nitroimidazoles are promising antimycobacterial agents known to inhibit both aerobic and anaerobic mycobacterial activity. Delamanid and pretomanid are two nitroimidazoles approved by the regulatory agencies for MDR-TB treatment. However, both agents possess unsatisfactory absorption and QTc prolongation. In our search for a safer nitroimidazole, we discovered JBD0131 (2). It exhibited excellent anti-mycobacterial activity against M. tuberculosis H37Rv in vitro and in vivo, improved PK and absorption, reduced QT prolongation potential of delamanid. JBD0131 is currently in clinical development in China for pulmonary tuberculosis (CTR20202308).
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Base de dados:
MEDLINE
Assunto principal:
Tuberculose Pulmonar
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Tuberculose Resistente a Múltiplos Medicamentos
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Mycobacterium tuberculosis
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Nitroimidazóis
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article