Combining symmetry elements results in potent naphthyridinone (NTD) HIV-1 integrase inhibitors

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6461-4. doi: 10.1016/j.bmcl.2011.08.082. Epub 2011 Sep 8.

Abstract

A series of naphthyridinone HIV-1 integrase strand-transfer inhibitors have been designed based on a psdeudo-C2 symmetry element present in the two-metal chelation pharmacophore. A combination of two distinct inhibitor binding modes resulted in potent inhibition of the integrase strand-transfer reaction in the low nM range. Effects of aryl and N1 substitutions are disclosed including the impact on protein binding adjusted antiviral activity.

MeSH terms

  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1
  • Naphthyridines / chemistry
  • Naphthyridines / pharmacology*

Substances

  • HIV Integrase Inhibitors
  • Naphthyridines