29095-13-4Relevant academic research and scientific papers
Optimization of N-benzyl-5-nitrofuran-2-carboxamide as an antitubercular agent
Gallardo-Macias, Ricardo,Kumar, Pradeep,Jaskowski, Mark,Richmann, Todd,Shrestha, Riju,Russo, Riccardo,Singleton, Eric,Zimmerman, Matthew D.,Ho, Hsin Pin,Dartois, Véronique,Connell, Nancy,Alland, David,Freundlich, Joel S.
, p. 601 - 606 (2019)
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 (MIC = 0.019–0.20 μM) against the Mycobacterium tuberculosis H37Rv strain and low in vitro cytotoxicity (CC50 = 40–>120 μM) 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 (MIC = 0.019 μM) and Vero cell cytotoxicity (CC50 > 120 μM). The findings suggest a rationale for the continued evolution of this promising series of antitubercular small molecules.
