Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 2

  • J Med Chem. 2004 Nov 18;47(24):5923-36. doi: 10.1021/jm040072r.
George A Freeman  1 ,  C Webster Andrews Iii 3rd ,  Andrew L Hopkins ,  Gina S Lowell ,  Lee T Schaller ,  Jill R Cowan ,  Stephen S Gonzales ,  George W Koszalka ,  Richard J Hazen ,  Lawrence R Boone ,  Rob G Ferris ,  Katrina L Creech ,  Grace B Roberts ,  Steven A Short ,  Kurt Weaver ,  David J Reynolds ,  John Milton ,  Jingshan Ren ,  David I Stuart ,  David K Stammers ,  Joseph H Chan
Affiliations
  • 1. GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA. [email protected]
PMID: 15537347 DOI: 10.1021/jm040072r
Abstract

HIV-1 nonnucleoside Reverse Transcriptase inhibitors (NNRTIs) are part of the combination therapy currently used to treat HIV Infection. The features of a new NNRTI drug for HIV treatment must include selective potent activity against both wild-type virus as well as against mutant virus that have been selected by use of current antiretroviral treatment regimens. Based on analogy with known HIV-1 NNRTI inhibitors and modeling studies utilizing the X-ray crystal structure of inhibitors bound in the HIV-1 RT, a series of substituted 2-quinolones was synthesized and evaluated as HIV-1 inhibitors.