Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection.
J Med Chem
; 57(5): 2033-46, 2014 03 13.
Article
em En
| MEDLINE
| ID: mdl-24320933
ABSTRACT
A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered. Optimization of antiviral potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Benzimidazóis
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Hepatite C
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Proteínas não Estruturais Virais
/
Fluorenos
Tipo de estudo:
Clinical_trials
Limite:
Animals
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Humans
/
Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article