Optimization of N-benzyl-5-nitrofuran-2-carboxamide as an antitubercular agent.
Bioorg Med Chem Lett
; 29(4): 601-606, 2019 02 15.
Article
em En
| MEDLINE
| ID: mdl-30600207
ABSTRACT
The optimization campaign for a nitrofuran antitubercular hit (N-benzyl-5-nitrofuran-2-carboxamide; JSF-3449) led to the design, synthesis, and biological profiling of a family of analogs. These compounds exhibited potent in vitro antitubercular activity (MICâ¯=â¯0.019-0.20⯵M) against the Mycobacterium tuberculosis H37Rv strain and low in vitro cytotoxicity (CC50â¯=â¯40->120⯵M) towards Vero cells. Significant improvements in mouse liver microsomal stability and mouse pharmacokinetic profile were realized by introduction of an α, α-dimethylbenzyl moiety. Among these compounds, JSF-4088 is highlighted due to its in vitro antitubercular potency (MICâ¯=â¯0.019⯵M) and Vero cell cytotoxicity (CC50â¯>â¯120⯵M). The findings suggest a rationale for the continued evolution of this promising series of antitubercular small molecules.
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Base de dados:
MEDLINE
Assunto principal:
Nitrofuranos
/
Antituberculosos
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article