Sutherland, HS;
Tong, AST;
Choi, PJ;
Conole, D;
Blaser, A;
Franzblau, SG;
Cooper, CB;
... Palmer, BD; + view all
(2018)
Structure-activity relationships for analogs of the tuberculosis drug bedaquiline with the naphthalene unit replaced by bicyclic heterocycles.
Bioorganic & Medicinal Chemistry
, 26
(8)
pp. 1797-1809.
10.1016/j.bmc.2018.02.026.
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Abstract
Replacing the naphthalene C-unit of the anti-tuberculosis drug bedaquiline with a range of bicyclic heterocycles of widely differing lipophilicity gave analogs with a 4.5-fold range in clogP values. The biological results for these compounds indicate on average a lower clogP limit of about 5.0 in this series for retention of potent inhibitory activity (MIC90s) against M.tb in culture. Some of the compounds also showed a significant reduction in inhibition of hERG channel potassium current compared with bedaquiline, but there was no common structural feature that distinguished these.
| Type: | Article |
|---|---|
| Title: | Structure-activity relationships for analogs of the tuberculosis drug bedaquiline with the naphthalene unit replaced by bicyclic heterocycles |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bmc.2018.02.026 |
| Publisher version: | https://doi.org/10.1016/j.bmc.2018.02.026 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemistry & Molecular Biology, Chemistry, Medicinal, Chemistry, Organic, Pharmacology & Pharmacy, Chemistry, Bedaquiline, Bedaquiline analogs, Tuberculosis, Drug development, MULTIDRUG-RESISTANT TUBERCULOSIS, MYCOBACTERIUM-TUBERCULOSIS, DIARYLQUINOLINES, ASSAY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10048730 |
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