Ethyl malonate amides: a diketo acid offspring fragment for HIV integrase inhibition

Bioorg Med Chem. 2011 Aug 15;19(16):5000-5. doi: 10.1016/j.bmc.2011.06.054. Epub 2011 Jun 29.

Abstract

While searching for new HIV integrase inhibitors we discovered that some ethyl malonate amides (EMA) are active against this enzyme. Surprisingly, the main function can only very rarely be found among the reported drug candidates. We synthesised a series of compounds in order to establish and analyse the structure-activity relationship. The similarity to the important classes of HIV integrase inhibitors as well as the synthetic availability of the different targets including this pharmacophore makes EMA compounds an interesting object of investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology
  • Data Mining
  • Drug Design
  • HIV Integrase / analysis
  • HIV Integrase / drug effects*
  • HIV Integrase / metabolism
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Keto Acids / chemical synthesis*
  • Keto Acids / chemistry
  • Malonates / chemical synthesis*
  • Malonates / chemistry
  • Malonates / pharmacology
  • Models, Molecular
  • Molecular Structure
  • Molecular Targeted Therapy
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Structure-Activity Relationship

Substances

  • Amides
  • Antiviral Agents
  • Carboxylic Acids
  • HIV Integrase Inhibitors
  • Keto Acids
  • Malonates
  • Quinolines
  • HIV Integrase