N-苯磺酰基-3-乙酰基吲哚羰基酰腙类衍生物合成及其体外抗HIV-1活性研究

Syntheses and In Vitro Anti-HIV-1 Activities of N-Phenylsulfonyl-3-acetylindole Carbonyl Hydrazone Derivatives

基于长期进行的抗HIV-1抑制剂研究,通过优化路线并设计合成了26个N-苯磺酰基-3-乙酰基吲哚羰基酰腙类衍生物(3a~3z)。该方法环保,为今后制备腙类化合物提供了绿色合成途径。所有目标化合物在体外均测定了其对HIV-1抑制活性。结果表明,化合物3a、3g、3t和3w~3y表现出较好的抗HIV-1活性,特别是N-苯磺酰基-3-乙酰基吲哚-3-甲基苯甲酰腙(3a)和N-(3-硝基)-苯磺酰基-3-乙酰基-6-甲基吲哚-2-噻吩甲酰腙(3t)表现出显著的抗HIV-1活性,其对应EC50值分别为0.77和0.74μg/mL,TI值分别为>259.74和>270.27。因此,化合物3a和3t可作为候选化合物经进一步结构优化研究其HIV-1活性。

As our ongoing work on research of anti-HIV-1 inhibitors,26 N-phenylsulfonyl-3-acetylindole carbonyl hydrazone derivatives 3 a~3 z were designed and prepared through a modified route.This procedure imbues the synthetic methodology with green credentials.All the target compounds were also well evaluated for their inhibitory activities against HIV-1 replication in vitro.The results demonstrated that compounds 3 a,3 g,3 t and 3 w~3 y display significant anti-HIV-1 activity.In particular,the N-phenylsulfonyl-3-acetylindole 3-methylbenzoyl hydrazone(3 a)and N-(3-nitro)phenylsulfonyl-3-acetyl-6-methylindole 2-thienylformyl hydrazine(3 t)exhibit the most potent anti-HIV-1 activity with EC50 values of 0.77 and 0.74μg/mL,and TI values of>259.74 and>270.27,respectively.Therefore,target compounds 3 a and 3 t might be identified as the promising candidates for further chemical optimization.