Exploring the SAR of the ß-Ketoacyl-ACP Synthase Inhibitor GSK3011724A and Optimization around a Genotoxic Metabolite.
ACS Infect Dis
; 6(5): 1098-1109, 2020 05 08.
Article
em En
| MEDLINE
| ID: mdl-32196311
ABSTRACT
In the course of optimizing a novel indazole sulfonamide series that inhibits ß-ketoacyl-ACP synthase (KasA) of Mycobacterium tuberculosis, a mutagenic aniline metabolite was identified. Further lead optimization efforts were therefore dedicated to eliminating this critical liability by removing the embedded aniline moiety or modifying its steric or electronic environment. While the narrow SAR space against the target ultimately rendered this goal unsuccessful, key structural knowledge around the binding site of this underexplored target for TB was generated to inform future discovery efforts.
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Base de dados:
MEDLINE
Assunto principal:
3-Oxoacil-(Proteína de Transporte de Acila) Sintase
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Compostos de Anilina
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Mycobacterium tuberculosis
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article