利巴韦林的氨磺酰衍生物的合成、结构及抗寄生虫活性

Synthesis, structure, and antiparasitic activity of sulfamoyl derivatives of ribavirin.

作者信息

Kini G D, Henry E M, Robins R K, Larson S B, Marr J J, Berens R L, Bacchi C J, Nathan H C, Keithly J S

机构信息

ICN-Nucleic Acid Research Institute, Costa Mesa, California 92627.

出版信息

J Med Chem. 1990 Jan;33(1):44-8. doi: 10.1021/jm00163a008.

DOI:10.1021/jm00163a008

PMID:2296034

Abstract

The triazole nucleoside derivatives 1-(5'-O-sulfamoyl-beta-D-ribofuranosyl) [1,2,4]triazole-3-carboxamide (2), 1-(5'-O-sulfamoyl-beta-D-ribofuranosyl) [1,2,4]triazole-3-thiocarboxamide (3), and 1-(5'-O-sulfamoyl-beta-D-ribofuranosyl)-[1,2,4]triazole-3- carbonitrile (4) were synthesized. Suitably protected triazole nucleosides were converted to their corresponding 5'-sulfamoyl derivatives, which on subsequent deprotection gave the desired compounds in good yields. The structures of compounds 2-4 were confirmed by X-ray crystallographic analysis. All three compounds showed significant antiparasitic activity in vitro, while 2 showed significant activity in vivo against Leishmania donovani and Trypanosoma brucei.

摘要

合成了三唑核苷衍生物1-(5'-O-氨磺酰基-β-D-呋喃核糖基)[1,2,4]三唑-3-甲酰胺(2)、1-(5'-O-氨磺酰基-β-D-呋喃核糖基)[1,2,4]三唑-3-硫代甲酰胺(3)和1-(5'-O-氨磺酰基-β-D-呋喃核糖基)-[1,2,4]三唑-3-腈(4)。将适当保护的三唑核苷转化为其相应的5'-氨磺酰基衍生物，随后脱保护，以良好的产率得到所需化合物。通过X射线晶体学分析确定了化合物2-4的结构。所有这三种化合物在体外均表现出显著的抗寄生虫活性，而化合物2在体内对杜氏利什曼原虫和布氏锥虫表现出显著活性。