Discovery of novel benzimidazolones as potent non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains

Bioorg Med Chem Lett. 2007 Apr 1;17(7):1956-60. doi: 10.1016/j.bmcl.2007.01.025. Epub 2007 Jan 19.

Abstract

Molecular modeling studies led to the rational discovery of N(1)-arylsulfonyl-1,3-dihydro-2H-benzimidazol-2-one as a novel template for the design of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are active against wild-type and mutant strains of HIV-1. It is worth noting that compound 3 proved to have antiretroviral activity similar to that of efavirenz and greater than that of nevirapine, two of the three NNRTIs currently available in antiretroviral therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Alkynes
  • Anti-Retroviral Agents / pharmacology*
  • Benzoxazines / pharmacology
  • Cell Line
  • Chemistry, Pharmaceutical / methods*
  • Cyclopropanes
  • Drug Design
  • Enzyme Inhibitors / pharmacology
  • HIV-1 / genetics*
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Conformation
  • Mutation*
  • Nevirapine / pharmacology
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology

Substances

  • Alkynes
  • Anti-Retroviral Agents
  • Benzoxazines
  • Cyclopropanes
  • Enzyme Inhibitors
  • Reverse Transcriptase Inhibitors
  • Nevirapine
  • efavirenz