Synthesis and evaluation of analogues of the tuberculosis drug bedaquiline containing heterocyclic B-ring units.
Bioorg Med Chem Lett
; 27(23): 5190-5196, 2017 12 01.
Article
em En
| MEDLINE
| ID: mdl-29107541
ABSTRACT
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 showed acceptable oral bioavailability, but there was only limited (and unpredictable) improvement in their hERG liability.
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Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Diarilquinolinas
/
Compostos Heterocíclicos
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Antituberculosos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2017
Tipo de documento:
Article