吡咯烷类神经氨酸酶抑制剂的设计、合成与初步活性研究

Design,Synthesis,and Activity Study of Pyrrolidine Derivatives as Neuraminidase Inhibitors

目的合成新型吡咯烷类神经氨酸酶抑制剂,并测定其抑制神经氨酸酶的活性。方法以L-羟脯氨酸为原料,合成一系列神经氨酸酶抑制剂,并用高通量活性筛选方法检测其对神经氨酸酶的抑制活性。结果设计、合成了18个新型的吡咯烷类化合物,其结构经核磁共振氢谱及质谱确定,并发现了几个具有较好活性的化合物。结论吡咯烷类化合物对神经氨酸酶有较高的抑制活性,值得进一步研究。

OBJECTIVE To synthesize a series of novel pyrrolidine derivatives as neuraminidase inhibitors and test their inhibitory activities against neuraminidase. METHODS A series of pyrrolidine derivatives were synthesized from L-hydroxyproline, and the neuraminidase inhibitory activities of these compounds were tested using high throughput screening. RESULRS 18 Pyrrolidine derivatives were designed and synthesized. The basic structures of these compounds were verified by ^1H-NMR and MS. Several compounds exhibited potent neuraminidase inhibitory activities. CONCLUSION Pyrrolidine derivatives exhibited potent neuraminidase inhibitory activities, and is worth of further investigation.