Synthesis of 5'-triphosphate mimics (P3Ms) of 3'-azido-3',5'-dideoxythymidine and 3',5'-dideoxy-5'-difluoromethylenethymidine as HIV-1 reverse transcriptase inhibitors

Nucleosides Nucleotides Nucleic Acids. 2005;24(3):179-89. doi: 10.1081/NCN-55707.

Abstract

3'-Azido-3',5-dideoxythymidine 5'-phosphonate and 3',5'-dideoxy-5'-difluoromethylenethymidine 5'-phosphonate were prepared by multistep syntheses. The nucleoside 5'-phosphonates were converted to their triphosphates and triphosphate mimics (P3Ms) containing beta,gamma-difluoromethylene, beta,gamma-dichloromethylene, or beta,gamma-imodo by condensation with pyrophosphate or pyrophosphate mimics, respectively. Inhibition of HIV-1 reverse transcriptase by the nucleoside P3Ms is briefly discussed.

MeSH terms

  • Dideoxynucleotides
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • Molecular Mimicry*
  • Molecular Structure
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Thymidine / analogs & derivatives*
  • Thymidine / chemical synthesis
  • Thymidine / chemistry
  • Thymidine / pharmacology
  • Thymine Nucleotides / chemical synthesis*
  • Thymine Nucleotides / chemistry
  • Thymine Nucleotides / pharmacology
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemical synthesis
  • Zidovudine / chemistry
  • Zidovudine / pharmacology

Substances

  • 3',5'-dideoxy-5'-difluoromethylenethymidine
  • Dideoxynucleotides
  • Reverse Transcriptase Inhibitors
  • Thymine Nucleotides
  • Zidovudine
  • zidovudine triphosphate
  • HIV Reverse Transcriptase
  • Thymidine