2. Academic Validation
  3. Respiratory syncytial virus fusion inhibitors. Part 4: optimization for oral bioavailability

Respiratory syncytial virus fusion inhibitors. Part 4: optimization for oral bioavailability

  • Bioorg Med Chem Lett. 2007 Feb 15;17(4):895-901. doi: 10.1016/j.bmcl.2006.11.063.
Kuo-Long Yu 1,  Ny Sin,  Rita L Civiello,  X Alan Wang,  Keith D Combrink,  H Belgin Gulgeze,  Brian L Venables,  J J Kim Wright,  Richard A Dalterio,  Lisa Zadjura,  Anthony Marino,  Sandra Dando,  Celia D'Arienzo,  Kathleen F Kadow,  Christopher W Cianci,  Zhufang Li,  Junius Clarke,  Eugene V Genovesi,  Ivette Medina,  Lucinda Lamb,  Richard J Colonno,  Zheng Yang,  Mark Krystal,  Nicholas A Meanwell
Affiliations

Affiliation

  • 1 Department of Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA.
PMID: 17169560 DOI: 10.1016/j.bmcl.2006.11.063
Abstract

A series of benzimidazole-based inhibitors of respiratory syncytial virus (RSV) fusion were optimized for Antiviral potency, membrane permeability and metabolic stability in human liver microsomes. 1-Cyclopropyl-1,3-dihydro-3-[[1-(4-hydroxybutyl)-1H-benzimidazol-2-yl]methyl]-2H-imidazo[4,5-c]pyridin-2-one (6m, BMS-433771) was identified as a potent RSV Inhibitor demonstrating good bioavailability in the mouse, rat, dog and cynomolgus monkey that demonstrated Antiviral activity in the BALB/c and cotton rat models of Infection following oral administration.

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