SYNTHESIS AND BROAD-SPECTRUM ANTIVIRAL ACTIVITY OF 7,8-DIHYDRO-7-METHYL-8-THIOXOGUANOSINE

被引：9

作者：

HENRY, EM ^{[1
]}

KINI, GD ^{[1
]}

LARSON, SB ^{[1
]}

ROBINS, RK ^{[1
]}

ALAGHAMANDAN, HA ^{[1
]}

SMEE, DF ^{[1
]}

机构：

[1] ICN,NUCL ACID RES INST,COSTA MESA,CA 92626

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 08期

关键词：

D O I：

10.1021/jm00170a013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

2,6,8-Trichloro-7-methylpurine (3) was converted to 2-chloro-8,9-dihydro-7-methyl-8-thioxopurin-6(lH)-one (5) by utilizing the difference in reactivity of the 2-, 6-, and 8-positions in the trichloropurine ring system to nucleophilic displacement. Compound 5 was subsequently glycosylated with l-0-acetyl-2,3,5-tri-0-benzoyl-D-ribofuranose according to the Vorbruggen procedure to yield 2-chloro-8,9-dihydro-7-methyl-9-(2,3,5-tri-0-benzoyl-β-D-ribofuranosyl)-8-thioxopurin-6(lH)-one (6). Removal of the benzoyl protecting groups, followed by amination of 7 with liquid ammonia at 150 °C, gave 7,8-dihydro-7-methyl-8-thioxoguanosine (2). The structure of compound 2 was confirmed by X-ray crystallographic analysis. Compounds 1 (7,8-dihydro-7-methyl-8-oxoguanosine) and 2 were evaluated for activity in various animal virus infection models. Against banzi, Semliki Forest, and San Angelo viruses in mice, 2 was highly active when administered before virus inoculation. © 1990, American Chemical Society. All rights reserved.

引用

页码：2127 / 2130

页数：4

共 26 条

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