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Novel Indazole Non-Nucleoside Reverse Transcriptase Inhibitors Using Molecular Hybridization Based on Crystallographic Overlays

2009; American Chemical Society; Volume: 52; Issue: 4 Linguagem: Inglês

10.1021/jm801322h

1520-4804

Lyn H. Jones, Gill Allan, Oscar Barba, Catherine Burt, Romuald Corbau, Thomas Dupont, Thorsten Knöchel, Steve Irving, Donald S. Middleton, Charles E. Mowbray, Manos Perros, H. Ringrose, Nigel A. Swain, Robert O. Webster, Mike Westby, Chris Phillips,

Biochemical and Molecular Research

A major problem associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of HIV is their lack of resilience to mutations in the reverse transcriptase (RT) enzyme. Using structural overlays of the known inhibitors efavirenz and capravirine complexed in RT as a starting point, and structure-based drug design techniques, we have created a novel series of indazole NNRTIs that possess excellent metabolic stability and mutant resilience.