Discovery of novel isoxazolines as anti-tuberculosis agents

Nitrofuranyl isoxazolines with increased proteolytic stability over nitrofuranyl amides were designed and synthesized leading to discovery of several compounds with potent in vitro anti-tuberculosis activity. However, their in vivo activity was limited by high protein binding and poor distribution. Consequently, a series of non-nitrofuran containing isoxazolines were prepared to determine if the core had residual anti-tuberculosis activity. This led to the discovery of novel isoxazoline 12 as anti-tuberculosis agent with a MIC90 value of 1.56 μg/mL.

Graphical abstractDiscovery of isoxazoline compound 12 as novel anti-tuberculosis agent (MIC90 = 1.56 μg/mL) is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide