Your browser doesn't support javascript.
loading
Benzimidazole-containing HCV NS5A inhibitors: effect of 4-substituted pyrrolidines in balancing genotype 1a and 1b potency.
Henderson, James A; Bilimoria, Darius; Bubenik, Monica; Cadilhac, Caroline; Cottrell, Kevin M; Dietrich, Evelyne; Denis, Francois; Ewing, Nigel; Falardeau, Guy; Giroux, Simon; Grey, Ronald; L'Heureux, Lucille; Liu, Bingcan; Mani, Nagraj; Morris, Mark; Nicolas, Olivier; Pereira, Oswy Z; Poisson, Carl; Govinda Rao, B; Reddy, T Jagadeeswar; Selliah, Subajini; Shawgo, Rebecca S; Vaillancourt, Louis; Wang, Jian; Yannopoulos, Constantin G; Chauret, Nathalie; Berlioz-Seux, Francoise; Chan, Laval C; Das, Sanjoy K; Grillot, Anne-Laure; Bennani, Youssef L; Maxwell, John P.
Afiliação
  • Henderson JA; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA. Electronic address: james_henderson@vrtx.com.
  • Bilimoria D; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Bubenik M; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Cadilhac C; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Cottrell KM; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Dietrich E; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Denis F; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Ewing N; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Falardeau G; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Giroux S; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Grey R; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • L'Heureux L; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Liu B; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Mani N; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Morris M; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Nicolas O; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Pereira OZ; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Poisson C; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Govinda Rao B; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Reddy TJ; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Selliah S; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Shawgo RS; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Vaillancourt L; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Wang J; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Yannopoulos CG; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Chauret N; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Berlioz-Seux F; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Chan LC; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Das SK; Vertex Pharmaceuticals Canada Incorporated, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada.
  • Grillot AL; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Bennani YL; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Maxwell JP; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
Bioorg Med Chem Lett ; 25(4): 944-7, 2015 Feb 15.
Article em En | MEDLINE | ID: mdl-25577041
ABSTRACT
The treatment of HCV with highly efficacious, well-tolerated, interferon-free regimens is a compelling clinical goal. Trials employing combinations of direct-acting antivirals that include NS5A inhibitors have shown significant promise in meeting this challenge. Herein, we describe our efforts to identify inhibitors of NS5A and report on the discovery of benzimidazole-containing analogs with subnanomolar potency against genotype 1a and 1b replicons. Our SAR exploration of 4-substituted pyrrolidines revealed that the subtle inclusion of a 4-methyl group could profoundly increase genotype 1a potency in multiple scaffold classes.
Assuntos
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Antivirais / Pirrolidinas / Benzimidazóis / Proteínas não Estruturais Virais Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Antivirais / Pirrolidinas / Benzimidazóis / Proteínas não Estruturais Virais Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2015 Tipo de documento: Article