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Novel benzophenones as non-nucleoside reverse transcriptase inhibitors of HIV-1. 2004
Joseph H Chan, and
George A Freeman, and
Jeffrey H Tidwell, and
Karen R Romines, and
Lee T Schaller, and
Jill R Cowan, and
Steve S Gonzales, and
Gina S Lowell, and
C W Andrews, and
David J Reynolds, and
Marty St Clair, and
Richard J Hazen, and
Rob G Ferris, and
Katrina L Creech, and
Grace B Roberts, and
Steven A Short, and
Kurt Weaver, and
George W Koszalka, and
Lawrence R Boone
GlaxoSmithKline Inc., 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA. joe.h.chan@gsk.com
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.
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