Herein, alkenylpiperidine and alkynylpiperidine moieties were introduced into the left wing of DAPYs (diarylpyrimidines) to explore the new site of the NNIBP (non-nucleoside inhibitor binding pocket) protein-solvent interface region via the structure-based drug design strategy. All the synthesized compounds displayed nanomolar to submicromolar activity against WT (wild-type) HIV-1. Among all, compound FT1 (EC₅₀ = 19 nM) was found to be the most active molecule, which is better than NVP (EC₅₀ = 0.10 μM). In addition, most of the compounds displayed micromolar activity against K103N and E138K mutant strains, while FT1 (EC_50(K103N) = 50 nM, EC_50(E138K) = 0.19 µM) still has the most effective activity. The molecular dynamics simulation studies revealed that the presence of pyridine moiety of FT1 was essential and played a significant role in its binding with RT (reverse transcriptase).

在此，烯基哌啶和炔基哌啶部分被引入 DAPYs（二芳基嘧啶）的左翼，通过基于结构的药物设计策略探索 NNIBP（非核苷抑制剂结合口袋）蛋白质-溶剂界面区域的新位点。所有合成的化合物对 WT（野生型）HIV-1 都显示出纳摩尔到亚微摩尔的活性。其中，化合物FT1 (EC ₅₀  = 19 nM) 是活性最强的分子，优于 NVP (EC ₅₀  = 0.10 μM)。此外，大多数化合物对 K103N 和 E138K 突变株表现出微摩尔活性，而FT1 (EC _50(K103N)  = 50 nM，EC_50(E138K)  = 0.19 µM) 仍然具有最有效的活性。分子动力学模拟研究表明，FT1的吡啶部分的存在是必不可少的，并且在其与 RT（逆转录酶）的结合中发挥了重要作用。