Novel benzophenones as non-nucleoside reverse transcriptase inhibitors of HIV-1

  • J Med Chem. 2004 Feb 26;47(5):1175-82. doi: 10.1021/jm030255y.
Joseph H Chan  1 ,  George A Freeman ,  Jeffrey H Tidwell ,  Karen R Romines ,  Lee T Schaller ,  Jill R Cowan ,  Steve S Gonzales ,  Gina S Lowell ,  C W Andrews 3rd ,  David J Reynolds ,  Marty St Clair ,  Richard J Hazen ,  Rob G Ferris ,  Katrina L Creech ,  Grace B Roberts ,  Steven A Short ,  Kurt Weaver ,  George W Koszalka ,  Lawrence R Boone
Affiliations
  • 1. GlaxoSmithKline Inc., 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA. [email protected]
PMID: 14971897 DOI: 10.1021/jm030255y
Abstract

GW4511, GW4751, and GW3011 showed IC50 values < or =2 nM against wild type HIV-1 and <10 nM against 16 mutants. They were particularly potent against NNRTI-resistant viruses containing Y181C-, K103N-, and K103N-based double mutations, which account for a significant proportion of the clinical failure of the three currently marketed NNRTIs. The Antiviral data together with the favorable pharmacokinetic data of GW4511 suggested that these benzophenones possess attributes of a new NNRTI drug candidate.