Jin KaiJun, Sang YaLi, De Clercq Erik, Pannecouque Christophe, Meng Ge
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai 200433, People's Republic of China.
Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Bioorg Med Chem Lett. 2018 Dec 1;28(22):3491-3495. doi: 10.1016/j.bmcl.2018.10.010. Epub 2018 Oct 9.
A novel series of substituted piperazine-1-yl-pyrimidine derivatives were designed and synthesized as a new type of HIV-1 non-nucleoside inhibitors. Various N-substituted aromatic groups were incorporated into the piperazine ring through a simple and practical route to investigate the biological activity of these target compounds against wild-type and resistant strains of HIV-1. All of the target compounds were also evaluated as HIV-1 reverse transcriptase inhibitors in MT-4 cell cultures. The biological results showed that six of these compounds displayed inhibitory activities against the wild-type strain, among of which 7q and 7t were found to be the two most active analogues possessing EC values of 31.50 μM and 3.36 μM, respectively. Molecular modeling studies of 7q provide valuable information for developing new anti-HIV-1 inhibitors.
设计并合成了一系列新型的取代哌嗪-1-基-嘧啶衍生物，作为新型HIV-1非核苷抑制剂。通过简单实用的路线将各种N-取代芳基引入哌嗪环，以研究这些目标化合物对HIV-1野生型和耐药菌株的生物活性。所有目标化合物还在MT-4细胞培养物中作为HIV-1逆转录酶抑制剂进行了评估。生物学结果表明，其中六种化合物对野生型菌株具有抑制活性，其中7q和7t被发现是两种活性最高的类似物，其EC值分别为31.50μM和3.36μM。7q的分子模拟研究为开发新型抗HIV-1抑制剂提供了有价值的信息。
