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Discovery of novel isoxazolines as anti-tuberculosis agents
Rajendra P Tangallapally1, Dianqing Sun, Rakesh
1Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Abstract:
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 MIC(90) value of 1.56microg/mL.
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