The synthesis of a series of 9-(2-phosphonomethoxyalkyl) derivatives of 6-(aminomethyl)purine 11, 2-amino-6-(aminomethyl)purine 12 and purine-6-carboxamidine 14 is reported. The 6-cyanopurines 1 and 2 were selectively alkylated with 2-[bis(isopropyloxy)phosphonylmethoxy]alkyl synthons 3 and 4 at the 9-position. Catalytic hydrogenation of the obtained 9-2-[bis(isopropyloxy)phosphonylmethoxy]alkyl}-6-cyanopurines 9 and 10 followed by treatment with bromotrimethylsilane afforded the title compounds 11 and 12. Analogous acyclic nucleotides derived from purine-6-carboxamidines 14 were prepared from the cyanopurines 9a and 10a by treatment with sodium methoxide and ammonium chloride followed by deprotection. Compounds 11 and 12 exhibited moderate activity (MIC50 = 3-50 μg/ml) against herpes simplex virus type 1, varicella-zoster virus and Moloney murine sarcoma virus in vitro.
报道了一系列9-(2-
磷酸甲氧基烷基)衍
生物6-(
氨甲基)
嘌呤 11、2-
氨基-6-(
氨甲基)
嘌呤 12和
嘌呤-6-羧酰胺
14的合成。6-
氰基
嘌呤 1和
2 在9位选择性地与2-[双(异丙氧基)
磷酰甲氧基]烷基合成物
3和
4 进行烷基化。得到的9-2-[双(异丙氧基)
磷酰甲氧基]烷基}-6-
氰基
嘌呤 9和
10 经过催化氢化,然后用
溴三甲基
硅烷处理得到标题化合物
11和
12。从
嘌呤-6-羧酰胺
14 衍生的类似的无环核苷酸是通过用
甲醇钠和
氯化铵处理
氰基
嘌呤 9a和
10a,然后去保护制备的。化合物
11和
12 在体外对单纯疱疹病毒1型、
水痘-带状疱疹病毒和莫洛尼小鼠肉瘤病毒表现出中等活性(MIC
50 = 3-50 μg/ml)。