Recent advances in the DABOs family as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

Curr Med Chem. 2011;18(16):2376-85. doi: 10.2174/092986711795843209.

Abstract

HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to an allosteric site on reverse transcriptase (RT) and are a key component of highly active anti-retroviral therapy (HAART) combination regimen for clinical treatment of HIV/AIDS. However, the rapid emergence of drug resistance has limited NNRTIs' clinical option. Therefore, there is an urgent need for the design and development of new and safe NNRTIs that are specifically active against drug-resistant viral strains. DABOs family is one representative of the reported potent HIV-1 NNRTIs, with robust anti-HIV-1 activity against both the wild-type (wt) and drug-resistant isolates carrying multiple RT gene mutations. Three generations of DABO analogues have been studied up to now, i.e.: dihydroalkyloxybenzyloxopyrimidines (O-DABOs), dihydroalkylthiobenzyloxopyrimidines (S-DABOs) and dihydroalkylaminodifluorobenzyloxopyrimidines (N-DABOs), from which many promising DABOs are under developed. The recent research of the DABOs family in antiviral activity, structure activity relationships (SAR), and interaction model with the HIV-1 RT are reviewed in this paper.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • Humans
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

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