Successful kinase bypass with new acyclovir phosphoramidate prodrugs

Bioorg Med Chem Lett. 2008 Aug 1;18(15):4364-7. doi: 10.1016/j.bmcl.2008.06.069. Epub 2008 Jun 24.

Abstract

Novel phosphoramidates of acyclovir have been prepared and evaluated in vitro against acyclovir-sensitive and -resistant herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV). Unlike the parent nucleoside these novel phosphate prodrugs retain antiviral potency versus the ACV-resistant virus strain, suggesting an efficient bypass of the viral thymidine kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir* / analogs & derivatives
  • Acyclovir* / chemical synthesis
  • Acyclovir* / chemistry
  • Acyclovir* / pharmacology
  • Acyclovir* / therapeutic use
  • Amides* / chemical synthesis
  • Amides* / chemistry
  • Amides* / pharmacology
  • Amides* / therapeutic use
  • Antiviral Agents* / chemical synthesis
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 2, Human / drug effects
  • Herpesvirus 3, Human
  • Humans
  • Molecular Structure
  • Phosphoric Acids* / chemical synthesis
  • Phosphoric Acids* / chemistry
  • Phosphoric Acids* / pharmacology
  • Phosphoric Acids* / therapeutic use
  • Prodrugs* / chemical synthesis
  • Prodrugs* / chemistry
  • Prodrugs* / pharmacology
  • Thymidine Kinase / metabolism*

Substances

  • Amides
  • Antiviral Agents
  • Phosphoric Acids
  • Prodrugs
  • phosphoramidic acid
  • Thymidine Kinase
  • Acyclovir