Synthesis and anti-HIV activity of some [Nucleoside Reverse Transcriptase Inhibitor]-C5'-linker-[Integrase Inhibitor] heterodimers as inhibitors of HIV replication

J Enzyme Inhib Med Chem. 2004 Dec;19(6):497-509. doi: 10.1080/14756360412331280554.

Abstract

Selected for their expected ability to inhibit HIV replication, a series of eight heterodimers containing a Nucleoside Reverse Transcriptase Inhibitor (NRTI) and an Integrase Inhibitor (INI), bound by a linker, were designed and synthesized. For the NRTIs, d4U, d2U and d4T were chosen. For the INIs, 4-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid (6) and 4-(3,5-dibenzyloxyphenyl)-2,4-dioxobutyric acid (9) (belonging to the beta-diketo acids class) were chosen. The conjugation of the two different inhibitors (NRTI and INI) was performed using an amino acid (glycine or beta-alanine) as a cleavable linker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Design
  • Drug Evaluation, Preclinical
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Reverse Transcriptase Inhibitors