A refined pharmacophore model for HIV-1 integrase inhibitors: Optimization of potency in the 1H-benzylindole series

  • Bioorg Med Chem Lett. 2008 May 1;18(9):2891-5. doi: 10.1016/j.bmcl.2008.03.089.
Laura De Luca  1 ,  Maria Letizia Barreca ,  Stefania Ferro ,  Nunzio Iraci ,  Martine Michiels ,  Frauke Christ ,  Zeger Debyser ,  Myriam Witvrouw ,  Alba Chimirri
Affiliations
  • 1. Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy.
PMID: 18417342 DOI: 10.1016/j.bmcl.2008.03.089
Abstract

We report herein the development of a new three-dimensional pharmacophore model for HIV-1 integrase inhibitors which led to the discovery of some 4-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acids that are able to specifically inhibit the strand transfer step of integration at nanomolar concentration. The synthesis of the new designed molecules is also described.