Bedaquiline is a 2012 FDA approved drug for the treatment of resistant tuberculosis (TB). It is the first TB drug in 40 years with a novel mechanism of action through inhibition of the mycobacterial ATP synthase enzyme. It demonstrates excellent efficacy against TB, but induces phospholipidosis at high doses, has a long terminal elimination half-life and exhibits potent hERG channel inhibition, resulting in clinical QTc interval prolongation.<sup> </sup>These serious side effects and drawbacks initiated the development of a second generation analogue.<br/>In collaboration with Global Alliance against Tuberculosis drug development, a number of second generation analogues of bedaquiline have been prepared and evaluated for their use as less toxic, more potent second generation compounds. SAR of new analogues and the selection process towards the preclinical candidate will be presented.

Next-generation bedaquiline for the treatment of tuberculosis

2019 Spring National Meeting

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