Journal article

Synthesis and evaluation of pyridine-derived bedaquiline analogues containing modifications at the A-ring subunit

Lisa Barbaro, Gayathri Nagalingam, James A Triccas, Lendl Tan, Nicholas P West, Jonathan B Baell, Daniel L Priebbenow



Despite promising efficacy, the clinical use of the anti-tubercular therapeutic bedaquiline has been restricted due to safety concerns. To date, limited SAR studies have focused on the quinoline ring (A-ring), and as such, we set out to explore modifications within this region in an attempt to discover new bedaquiline variants with an improved safety profile. We herein report the development of unique synthetic strategies that facilitated access to novel bedaquiline analogues leading to the discovery that anti-tubercular activity could be retained following replacement of the quinoline motif with pyridine heterocycles. This discovery is anticipated to open up multiple new avenues for explora..

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University of Melbourne Researchers


Awarded by Australian Research Council

Awarded by National Health and Medical Research Council of Australia (NHMRC)

Funding Acknowledgements

JBB and DLP acknowledge the generous funding support of the Australian Research Council (DP140103996 and DE200100949, respectively). The National Health and Medical Research Council of Australia (NHMRC) is thanked for Fellowship support for JBB (2012-2016 Senior Research Fellowship #1020411, 2017 - Principal Research Fellowship #1117602). The Australian Translational Medicinal Chemistry Facility (ATMCF) within Monash Institute of Pharmaceutical Sciences (MIPS), acknowledges the support of the Australian Government's National Collaborative Research Infrastructure Strategy (NCRIS) program via Therapeutic Innovation Australia (TIA).