Design and optimisation of orally active TLR7 agonists for the treatment of hepatitis C virus infection

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2389-93. doi: 10.1016/j.bmcl.2011.02.092. Epub 2011 Mar 16.

Abstract

The synthesis and structure-activity relationships of a series of novel interferon inducers are described. Pharmacokinetic studies and efficacy assessment of a series of 8-oxo-3-deazapurine analogues led to the identification of compound 33, a potent and selective agonist of the TLR7 receptor with an excellent in vivo efficacy profile in a mouse model.

MeSH terms

  • Administration, Oral
  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / therapeutic use
  • Drug Design
  • Hepacivirus / drug effects*
  • Mice
  • Models, Animal
  • Purines / chemistry*
  • Purines / pharmacokinetics
  • Purines / therapeutic use
  • RNA Virus Infections / drug therapy*
  • Rats
  • Structure-Activity Relationship
  • Toll-Like Receptor 7 / agonists*
  • Toll-Like Receptor 7 / metabolism

Substances

  • Antiviral Agents
  • Purines
  • Toll-Like Receptor 7