Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 2.
Journal of medicinal chemistry 2004 Nov 18; 47(24):5923-36
Freeman G GA, Andrews Iii C CW, Hopkins A AL, Lowell G GS, Schaller L LT, Cowan J JR, Gonzales S SS, Koszalka G GW, Hazen R RJ, Boone L LR, Ferris R RG, Creech K KL, Roberts G GB, Short S SA, Weaver K K, Reynolds D DJ, Milton J J, Ren J J, Stuart D DI, Stammers D DK, Chan J JH
GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA. Andy.A.Freeman@gsk.com
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.