Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 2.
Freeman GA., Andrews Iii CW., Hopkins AL., Lowell GS., Schaller LT., Cowan JR., Gonzales SS., Koszalka GW., Hazen RJ., Boone LR., Ferris RG., Creech KL., Roberts GB., Short SA., Weaver K., Reynolds DJ., Milton J., Ren J., Stuart DI., Stammers DK., Chan JH.
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.