Respiratory syncytial virus fusion inhibitors. Part 6: an examination of the effect of structural variation of the benzimidazol-2-one heterocycle moiety

Bioorg Med Chem Lett. 2007 Sep 1;17(17):4784-90. doi: 10.1016/j.bmcl.2007.06.065. Epub 2007 Jun 26.

Abstract

The effect of structural variation of the benzimidazol-2-one ring of RSV fusion inhibitors related to BMS-433771 (1) was examined in conjunction with side chain modifications and the introduction of an aminomethyl substituent at the 5-position of the core benzimidazole moiety. Replacement of the benzimidazol-2-one moiety with benzoxazole, oxindole, quinoline-2-one, quinazolin-2,4-dione and benzothiazine derivatives provided a series of potent RSV fusion inhibitors 4. However, the intrinsic potency of 6,6-fused ring systems was generally less than that of comparably substituted 5,6-fused heterocycles of the type found in BMS-433771 (1). The introduction of an aminomethyl substituent to the benzimidazole ring enhanced antiviral activity in the 6,6-fused ring systems.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Electrons
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Models, Molecular
  • Molecular Conformation
  • Respiratory Syncytial Virus Infections / drug therapy*
  • Respiratory Syncytial Viruses / metabolism*
  • Viral Fusion Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • BMS 433771
  • Benzimidazoles
  • Viral Fusion Proteins
  • benzimidazole