Design and synthesis of dual inhibitors of HIV reverse transcriptase and integrase: introducing a diketoacid functionality into delavirdine

Bioorg Med Chem. 2008 Apr 1;16(7):3587-95. doi: 10.1016/j.bmc.2008.02.007. Epub 2008 Feb 8.


Cost and toxicity problems associated with highly active antiretroviral therapy (HAART) in HIV/AIDS treatment could be alleviated by using designed multiple ligands (DMLs). Dual inhibitors of HIV reverse transcriptase (RT) and integrase (IN) were rationally designed by introducing a diketoacid (DKA) functionality into the tolerant C-5 site of RT inhibitor delavirdine. The resulting compounds all demonstrate good activity against both RT and IN in enzymatic assays and HIV in cell-based assay, whereas their C-7 regioisomers are all inactive in these assays. Balanced activities were observed with C-3 halogenated inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Delavirdine / chemistry*
  • Drug Design*
  • HIV / drug effects
  • HIV / enzymology
  • HIV Integrase / metabolism
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / metabolism
  • Keto Acids / chemistry*
  • Molecular Structure
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*


  • HIV Integrase Inhibitors
  • Keto Acids
  • Reverse Transcriptase Inhibitors
  • Delavirdine
  • HIV Integrase
  • HIV Reverse Transcriptase