Synthesis and evaluation of analogues of the tuberculosis drug bedaquiline containing heterocyclic B-ring units.
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ABSTRACT:
SUBMITTER: Choi PJ
PROVIDER: S-EPMC5696560 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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Synthesis and evaluation of analogues of the tuberculosis drug bedaquiline containing heterocyclic B-ring units.
Choi Peter J PJ Sutherland Hamish S HS Tong Amy S T AST Blaser Adrian A Franzblau Scott G SG Cooper Christopher B CB Lotlikar Manisha U MU Upton Anna M AM Guillemont Jerome J Motte Magali M Queguiner Laurence L Andries Koen K Van den Broeck Walter W Denny William A WA Palmer Brian D BD
Bioorganic & medicinal chemistry letters 20171020 23
Analogues of bedaquiline where the phenyl B-unit was replaced with monocyclic heterocycles of widely differing lipophilicity (thiophenes, furans, pyridines) were synthesised and evaluated. While there was an expected broad positive correlation between lipophilicity and anti-TB activity, the 4-pyridyl derivatives appeared to have an additional contribution to antibacterial potency. The majority of the compounds were (desirably) more polar and had higher rates of clearance than bedaquiline, and sh ...[more]
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