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Structure-activity relationships for analogs of the tuberculosis drug bedaquiline with the naphthalene unit replaced by bicyclic heterocycles.

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.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Sutherland HS,Tong AST,Choi PJ,Conole D,Blaser A,Franzblau SG,Cooper CB,Upton AM,Lotlikar MU,Denny WA,Palmer BD

doi

10.1016/j.bmc.2018.02.026

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

1797-1809

issue

8

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(17)32339-8

journal_volume

26

pub_type

杂志文章

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