新型异-D-2',3'-二脱氧-3'-氟硫代核苷衍生物作为拉米夫定生物电子等排体的设计、对映体纯合成及生物学评价

Design, enantiopure synthesis, and biological evaluation of novel iso-D-2',3'-dideoxy-3'-fluorothianucleoside derivatives as a bioisostere of lamivudine.

作者信息

Kim Kyung Ran, Park Ah-Young, Moon Hyung Ryong, Chun Moon Woo, Jeong Lak Shin

机构信息

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, Korea.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2007;26(8-9):911-5. doi: 10.1080/15257770701506426.

DOI:10.1080/15257770701506426

PMID:18058507

Abstract

Novel iso D-2',3'-dideoxythianucleoside derivatives 1-3 were designed and asymmetrically synthesized to search for new anti-HIV agents. Final compounds 1-3 were evaluated against a variety of viruses including HIV-1 and 2. Only cytosine analog 3 showed a potent anti-VSV activity (EC(50) = 9.43 microg/mL). This result implies that iso 2',3'-dideoxy sugar templates might play a role of a sugar surrogate of nucleosides for the development of anti-RNA virus agent.

摘要

设计并不对称合成了新型异-D-2'，3'-二脱氧硫代核苷衍生物1-3，以寻找新型抗HIV药物。对最终化合物1-3针对包括HIV-1和2在内的多种病毒进行了评估。只有胞嘧啶类似物3显示出有效的抗VSV活性（EC(50)=9.43微克/毫升）。该结果表明，异-2'，3'-二脱氧糖模板可能在开发抗RNA病毒药物中充当核苷糖替代物的角色。