2-hydroxyisoquinoline-1,3(2H,4H)-diones as inhibitors of HIV-1 integrase and reverse transcriptase RNase H domain: influence of the alkylation of position 4.

@article{Billamboz20112hydroxyisoquinoline132H4Hdiones,
  title={2-hydroxyisoquinoline-1,3(2H,4H)-diones as inhibitors of HIV-1 integrase and reverse transcriptase RNase H domain: influence of the alkylation of position 4.},
  author={Muriel Billamboz and Fabrice Bailly and Cedric Lion and Christina Calmels and M L Andr{\'e}ola and Myriam Witvrouw and Frauke Christ and Zeger Debyser and Laura De Luca and Alba Chimirri and Philippe Cotelle},
  journal={European journal of medicinal chemistry},
  year={2011},
  volume={46 2},
  pages={535-46}
}
We report herein the synthesis of a series of fifteen 2-hydroxyisoquinoline-1,3(2H,4H)-dione derivatives. Alkyl and arylalkyl groups were introduced on position 4 of the basis scaffold. All the compounds presented poor inhibitory properties against HIV-1 reverse transcriptase ribonuclease H (RNase H). Four compounds inhibited HIV-1 integrase at a low micromolar level. A docking study using the later crystallographic data available for PFV integrase allowed us to explain the slightly improved… CONTINUE READING