A new series of pyridinone derivatives as potent non-nucleoside human immunodeficiency virus type 1 specific reverse transcriptase inhibitors

J Med Chem. 1995 Nov 10;38(23):4679-86. doi: 10.1021/jm00023a007.

Abstract

4-(Arylthio)-pyridin-2(1H)-ones variously substituted in their 3-, 5-, and 6-positions have been synthesized as a new series of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)-pyridinone hybrid molecules. Biological studies revealed that some of them show potent HIV-1 specific reverse transcriptase inhibitory properties. Compounds 16 and 7c, the most active ones, inhibit the replication of HIV-1 at 3 and 6 nM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • HIV Reverse Transcriptase
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • HIV-1 / physiology
  • HIV-2 / enzymology
  • Kinetics
  • Molecular Structure
  • Pyridones / chemical synthesis*
  • Pyridones / pharmacology
  • RNA-Directed DNA Polymerase / metabolism*
  • Recombinant Proteins / antagonists & inhibitors
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • 3-amino-5-ethyl-6-methyl-4-((3',5'-dimethylphenyl)thio)pyridin-2(1H)-one
  • 5-ethyl-6-methyl-3-nitro-4-((3',5'-dimethylphenyl)thio)pyridin-2(1H)-one
  • Antiviral Agents
  • Pyridones
  • Recombinant Proteins
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase