9-[(1,3-二羟基-2-丙氧基)甲基]鸟嘌呤：一种新型强效选择性抗疱疹剂。

9-[(1,3-Dihydroxy-2-propoxy)methyl]guanine: a new potent and selective antiherpes agent.

作者信息

Martin J C, Dvorak C A, Smee D F, Matthews T R, Verheyden J P

出版信息

J Med Chem. 1983 May;26(5):759-61. doi: 10.1021/jm00359a023.

Abstract

The synthesis of a new acyclic analogue of deoxyguanosine, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 1), is described starting from epichlorohydrin via condensation of 2-O-(acetoxymethyl)-1,3-di-O-benzylglycerol (5) with N2,9-diacetylguanine (6). In vitro studies indicate that DHPG is a potent and broad-acting (herpes simplex virus types 1 and 2, cytomegalovirus, and Epstein-Barr virus) antiherpetic agent. In vivo studies indicate its lack of toxicity [LD50 (mice) = 1-2 g/kg, ip] and its superiority over acyclovir [oral ED50 = 7 (mg/kg)/day vs. 550 (mg/kg)/day in HSV-2 infected mice].

摘要

描述了一种新的脱氧鸟苷无环类似物9-[(1,3-二羟基-2-丙氧基)甲基]鸟嘌呤（DHPG，1）的合成方法，该方法从环氧氯丙烷开始，通过2-O-(乙酰氧基甲基)-1,3-二-O-苄基甘油（5）与N2,9-二乙酰鸟嘌呤（6）缩合得到。体外研究表明，DHPG是一种强效且作用广泛的抗疱疹剂（对1型和2型单纯疱疹病毒、巨细胞病毒和爱泼斯坦-巴尔病毒有效）。体内研究表明其无毒[半数致死量（小鼠）=1-2 g/kg，腹腔注射]，并且比阿昔洛韦更具优势[在单纯疱疹病毒2型感染的小鼠中，口服半数有效剂量=7（mg/kg）/天，而阿昔洛韦为550（mg/kg）/天]。