Des-A-ring benzothiadiazines: inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase.
Bioorg Med Chem Lett
; 18(8): 2735-8, 2008 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-18362072
ABSTRACT
In our program to discover non-nucleoside, small molecule inhibitors of genotype 1 HCV polymerase, we investigated a series of promising analogs based on a benzothiadiazine screening hit that contains an ABCD ring system. After demonstrating that a methylsulfonylamino D-ring substituent increased the enzyme potency into the low nanomolar range, we explored a minimum core required for activity by truncating to a three-ring system. Described herein are the syntheses and structure-activity relationship of a set of inhibitors lacking the A-ring of an ABCD ring system. We observed that small aromatic rings and alkenyl groups appended to the 5-position of the B-ring were optimal, resulting in inhibitors with low nanomolar potencies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzotiadiazinas
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RNA Polimerase Dependente de RNA
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Proteínas não Estruturais Virais
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Hepacivirus
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Inibidores Enzimáticos
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article