Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda6-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones: Part 4. Optimization of DMPK properties

Bioorg Med Chem Lett. 2008 Jun 1;18(11):3421-6. doi: 10.1016/j.bmcl.2008.04.005. Epub 2008 Apr 4.

Abstract

5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as potent inhibitors of genotype 1 HCV NS5B polymerase focusing on the optimization of their drug metabolism and pharmacokinetics (DMPK) profiles. This investigation led to the discovery of potent inhibitors with improved DMPK properties.

MeSH terms

  • Administration, Oral
  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacokinetics*
  • Combinatorial Chemistry Techniques
  • Drug Design
  • Haplorhini
  • Hepacivirus / enzymology*
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Structure
  • Pyridazines / chemical synthesis*
  • Pyridazines / chemistry
  • Pyridazines / pharmacokinetics*
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Pyridazines
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus