摘要：In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines(NP-DATAs),synthesis of a series of novel biphenyl-substituted diaryltriazines(BP-DATAs)with a flexible side chain attached at the C-6 position is *** compounds exhibited excellent potency against wild-type(WT)HIV-1 with EC50 values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant *** 5 j and 6 k had the best activity against WT,single and double HIV-1 mutants and reverse transcriptase(RT)enzyme comparable to two reference drugs(EFV and ETR)and our lead compound NP-DATA(1).Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket(NNIBP)attributing to the improved *** preliminary structure-activity relationship and PK profiles were also discussed.

摘要：我们以已上市的etravirine和正在临床研究的VRX-480773两个逆转录酶抑制剂为模板，通过杂交这两个化合物的药效团，获得含酰胺片段的S—DAPYs类似物，该类似物对野生型HIV-1病毒株具有中等强度抑制活性．而Maurizio所发现的另一类无酰胺片段的***类似物却表现出优异的抑制活性．为了考察酰胺片段对S-DAPYs类似物抑制HIV-1活性的影响，本文合成了一系列无酰胺片段的S—DAPYs类似物．生物活性结果表明，3个化合物（6g、6m和6s）对野生型HIV-1具有中等强度抑制活性（EC50在6．5～15．4μmol／L范围内），弱于相应的具有酰胺片段的类似物．此外，分子模拟还揭示了酰胺片段可与K103形成至关重要的氢键作用，这为新型非核苷类逆转录酶抑制剂的设计奠定了理论基础．

摘要：在已有工作基础上,基于分子对接设计合成了8个新的4-烯丙基取代和4-叠氮基取代的二芳基三嗪类衍生物。抗HIV-1活性的测试结果表明所有新化合物均具有抗HIV-1活性。其中化合物7c不仅抑制HIV-1野生株的复制(IC50=0.034μmol·L-1,SI=6475),且对Y181C和K103C双突变酶显示出较强的抑制活性,其IC50值为9.39μmol·L-1,高于奈韦拉平。