1-benzoyl-2-(2-nitrophenyl)-1h-benzimidazole derivatives: A novel approach to the development of new hiv-1 reverse transcriptase inhibitors

• DAVID VÁSQUEZ ^[1] ; CARLOS F LAGOS ^[1] ; JAIME MELLA-RAIPÁN ^[1] ; LUIS GONZÁLEZ ^[1] ; ROBERTO EBENSPERGER ^[1] ; M. JAVIERA ALVAREZ-FIGUEROA ^[1] ; EDMUNDO SÁEZ ^[1] ; HERNÁN PESSOA-MAHANA ^[2] ; RAÚL ARAYA-SECCHP ^[1] ; ANGEL GONZÁLEZ-WONG ^[1] ; TOMÁS PÉREZ-ACLE ^[1] ; C. DAVID PESSOA-MAHANA ^[1]
  1. [1] Pontificia Universidad Católica de Chile

     Pontificia Universidad Católica de Chile

     Santiago, Chile

     
  2. [2] Universidad de Chile

     Universidad de Chile

     Santiago, Chile

     
• Localización: Journal of the Chilean Chemical Society (Boletín de la Sociedad Chilena de Química), ISSN-e 0717-6309, ISSN 0366-1644, Vol. 52, Nº. 4, 2007, págs. 1281-1287
• Idioma: inglés
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• Resumen

  • A novel approach to the development of a new class of HIV-1 RT inhibitors is reported. The 1-benzoyl-2-aryl-1H-benzimidazole series was designed as a combination of two previously reported active scaffolds, the benzimidazole and benzoyl moieties. The active compounds of the series effectively blocked the reverse transcription in the micromolar range in an in vitro assay containing the wild-type enzyme. We have demonstrated that the 2-nitrophenyl C-2 substituent is an important structural feature for the desired biological activity in this series. Molecular docking experiments suggest that the active compounds adopt a butterflylike conformation within the binding pocket of the enzyme, with the benzoyl moiety located in an extended hydrophobic region defined mainly by Tyrl 81, Tyrl 88, and Trp229