新型苯丙氨酸三肽衍生物的合成及其抗乙肝病毒活性  

Synthesis and Anti-hepatitis B Virus Activities of Novel Phenylalanine Tripeptide Derivatives

作　　者：曾晓萍[1,2] 安巧[1,2] 邱净英 曹佩雪[1,2] 潘卫东 夏文 徐必学[1,2] 梁光义[1,2] 胡占兴 ZENG Xiao-ping;AN Qiao;QIU Jing-ying;CAO Pei-xue;PAN Wei-dong;XIA Wen;XU Bi-xue;LIANG Guang-yi;HU Zhan-xing(State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University, Guiyang 550014,China;The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002,China;Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University,Xuzhou 221004,China;Guizhou Bailing Enterprise Group Pharmaceutical Co.,Ltd.,Anshun 561000, China)

机构地区：[1]贵州医科大学省部共建药用植物功效与利用国家重点实验室,贵州贵阳550014 [2]贵州省中国科学院天然产物化学重点实验室,贵州贵阳550002 [3]徐州医科大学江苏省新药研究与临床药学重点实验室,江苏徐州221004 [4]贵州百灵企业集团制药股份有限公司,贵州安顺561000

出　　处：《合成化学》2018年第12期873-882,894,共11页Chinese Journal of Synthetic Chemistry

基　　金：国家重大新药创制科技重大专项(2011ZX09102-009-002);贵州省科技合作计划项目(黔科合LH字[2015]7405);重大新药创制(2015ZX09101012);黔科合重大专项([2015]6002)

摘　　要：以具有抗HBV活性的苯丙氨酸二肽化合物马蹄金素(MTS)为先导化合物,设计并合成了23个新型的苯丙氨酸三肽衍生物(4a～4h,5,6a,6b和8a～8k),其结构经1H NMR,13C NMR和MS(ESI)表征。采用Hep G22. 2. 15细胞为乙肝病毒载体,评价了目标化合物的抗HBV活性。结果表明:化合物5 (IC50=2. 98μM)、6b(IC50=0. 62μM)和8k(IC50=5. 07μM)对HBV DNA复制的抑制活性优于MTS(IC50=11. 16μM)。A series of phenylalanine tripeptide derivatives with structural novelty were designed and synthesized using Matijin-Su(MTS)as the lead compound.The structures were characterized by^1H NMR,^13C NMR and MS(ESI),and all the target compounds were evaluated for their inhibitory effects against the replication of hepatitis B virus(HBV)DNA in HepG22.2.15cells.The results showed that compounds5(IC50=2.98μM),6b(IC50=0.62μM) and 8k(IC50=5.07μM) exhibited significant inhibition activities on the replication of HBV DNA in2.2.15cells,better than the lead compound MTS(IC50=11.16μM).

关 键 词：马蹄金素 苯丙氨酸三肽衍生物 合成 抗乙肝病毒活性 

分 类 号：O624.6[理学—有机化学]