Eastern extension of azoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase; cyano group alternatives

  • Bioorg Med Chem Lett. 2010 Apr 15;20(8):2485-8. doi: 10.1016/j.bmcl.2010.03.006.
Cheryl S Leung  1 ,  Jacob G Zeevaart ,  Robert A Domaoal ,  Mariela Bollini ,  Vinay V Thakur ,  Krasimir A Spasov ,  Karen S Anderson ,  William L Jorgensen
Affiliations
  • 1. Department of Chemistry, Yale University, New Haven, CT 06520, USA.
PMID: 20304641 DOI: 10.1016/j.bmcl.2010.03.006
Abstract

Design of non-nucleoside inhibitors of HIV-1 Reverse Transcriptase is being pursued with the assistance of free energy perturbation (FEP) calculations to predict relative free energies of binding. Extension of azole-containing inhibitors into an 'eastern' channel between Phe227 and Pro236 has led to the discovery of potent and structurally novel derivatives.