Freeman George A, Andrews Iii C Webster, Hopkins Andrew L, Lowell Gina S, Schaller Lee T, Cowan Jill R, Gonzales Stephen S, Koszalka George W, Hazen Richard J, Boone Lawrence R, Ferris Rob G, Creech Katrina L, Roberts Grace B, Short Steven A, Weaver Kurt, Reynolds David J, Milton John, Ren Jingshan, Stuart David I, Stammers David K, Chan Joseph H
GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA.
J Med Chem. 2004 Nov 18;47(24):5923-36. doi: 10.1021/jm040072r.
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.
HIV-1非核苷类逆转录酶抑制剂（NNRTIs）是目前用于治疗HIV感染的联合疗法的一部分。一种用于治疗HIV的新型NNRTI药物的特性必须包括对野生型病毒以及对通过使用当前抗逆转录病毒治疗方案筛选出的突变病毒具有选择性强效活性。基于与已知HIV-1 NNRTI抑制剂的类比以及利用结合在HIV-1逆转录酶中的抑制剂的X射线晶体结构进行的建模研究，合成了一系列取代的2-喹诺酮并将其作为HIV-1抑制剂进行评估。
