306761-54-6Relevant articles and documents
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.
supporting information, p. 601 - 606 (2019/01/04)
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.
Rapid Ti(Oi-Pr)4 facilitated synthesis of α,α,α-trisubstituted primary amines by the addition of Grignard reagents to nitriles under microwave heating conditions
Wang, Ruifang,Gregg, Brian T.,Zhang, Wei,Golden, Kathryn C.,Quinn, John F.,Cui, Peng,Tymoshenko, Dmytro O.
experimental part, p. 7070 - 7073 (2010/03/01)
A series of carbinamines (α,α,α-trisubstituted amines) have been prepared in a simple and efficient one-pot procedure by the addition of Grignard reagents to a series of aliphatic, aromatic and heteroaromatic nitriles. The resulting magnesium imines are subsequently converted to the desired amine after treatment with Ti(Oi-Pr)4 and additional microwave heating. Key to this procedure is the use of microwave heating for both steps of the reaction protocol, which significantly improves both reaction yields and reduces reaction times. In general, the Grignard addition reaction is complete within 5-10 min at 100 °C followed by conversion with Ti(Oi-Pr)4 and additional microwave heating to give the target amines in good yields.