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2-N-Arylthiazole inhibitors of Mycobacterium tuberculosis.
Clark, Michael P; Wang, Tiansheng; Perola, Emanuele; Deininger, David D; Zuccola, Harmon J; Jones, Steven M; Gao, Hong; VanderVen, Brian C; Russell, David G; Shoen, Carolyn M; Cynamon, Michael H; Thomson, John A; Locher, Christopher P.
Afiliación
  • Clark MP; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA. Electronic address: michael_clark@vrtx.com.
  • Wang T; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Perola E; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Deininger DD; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Zuccola HJ; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • Jones SM; Contrafect Corporation, Yonkers, NY 10701, USA.
  • Gao H; Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
  • VanderVen BC; Dept of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
  • Russell DG; Dept of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
  • Shoen CM; Central New York Research Corporation, Syracuse, NY 13210, USA.
  • Cynamon MH; Central New York Research Corporation, Syracuse, NY 13210, USA.
  • Thomson JA; P.O. Box 2241, Acton, MA 01720, USA.
  • Locher CP; Versatope Therapeutics Inc, Boston, MA 02210, USA.
Bioorg Med Chem Lett ; 27(17): 3987-3991, 2017 09 01.
Article en En | MEDLINE | ID: mdl-28778468
ABSTRACT
To develop agents for the treatment of infections caused by Mycobacterium tuberculosis, a novel phenotypic screen was undertaken that identified a series of 2-N-aryl thiazole-based inhibitors of intracellular Mycobacterium tuberculosis. Analogs were optimized to improve potency against an attenuated BSL2 H37Ra laboratory strain cultivated in human macrophage cells in vitro. The insertion of a carboxylic acid functionality resulted in compounds that retained potency and greatly improved microsomal stability. However, the strong potency trends we observed in the attenuated H37Ra strain were inconsistent with the potency observed for virulent strains in vitro and in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 3_ND Problema de salud: 3_neglected_diseases / 3_tuberculosis Asunto principal: Tiazoles / Antibacterianos / Mycobacterium tuberculosis Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2017 Tipo del documento: Article
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 3_ND Problema de salud: 3_neglected_diseases / 3_tuberculosis Asunto principal: Tiazoles / Antibacterianos / Mycobacterium tuberculosis Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2017 Tipo del documento: Article