Ugarkar B G, Cottam H B, McKernan P A, Robins R K, Revankar G R
J Med Chem. 1984 Aug;27(8):1026-30. doi: 10.1021/jm00374a015.
Several pyrazolo[3,4-d]pyrimidine-4(5H)-selone ribonucleosides were prepared as potential antiparasitic agents. Treatment of 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine (5a) with selenourea and subsequent deacetylation gave 1-beta-D-ribofuranosylpyrazolo[3,4-d] pyrimidine-4(5H)-selone (6a). A similar treatment of 3-bromo-4-chloro-1-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyrazolo [3,4-d]pyrimidine (5b) with selenurea, followed by debenzoylation, gave the 3-bromo derivative of 6a (6b). Glycosylation of persilylated 4-chloro-6-methyl-pyrazolo [3,4-d]pyrimidine (7) with tetra-O-acetylribofuranose (8) provided the key intermediate 4-chloro-6-methyl-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl) pyrazolo[3,4-d]pyrimidine (9). Ammonolysis of 9 gave 4-amino-6-methyl-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidine (10), whereas treatment with sodium hydroxide gave 6-methylallopurinol ribonucleoside (11a). Reaction of 9 with either thiourea or selenourea, followed by deacetylation, provided 6-methylpyrazolo[3,4-d]pyrimidine-4(5H)-thione ribonucleoside (11c) and the corresponding seleno derivative (11d), respectively. The structural assignment of these nucleosides was made on the basis of spectral studies. These compounds were tested in vitro against certain viruses and tumor cells. All the compounds except 11c exhibited significant activity against HSV-2 in vitro, whereas 11c exhibited the most potent activity against measles and has a very low toxicity. Compounds 6a, 6b, and 11d were found to be potent inhibitors of growth of L1210 and P388 leukemia in vitro.
制备了几种吡唑并[3,4 - d]嘧啶 - 4(5H) - 硒酮核糖核苷作为潜在的抗寄生虫剂。用硒脲处理4 - 氯 - 1 - (2,3,5 - 三 - O - 乙酰基 - β - D - 呋喃核糖基)吡唑并[3,4 - d]嘧啶(5a)，随后进行脱乙酰化反应，得到1 - β - D - 呋喃核糖基吡唑并[3,4 - d]嘧啶 - 4(5H) - 硒酮(6a)。用硒脲对3 - 溴 - 4 - 氯 - 1 - (2,3,5 - 三 - O - 苯甲酰基 - β - D - 呋喃核糖基)吡唑并[3,4 - d]嘧啶(5b)进行类似处理，随后进行脱苯甲酰化反应，得到6a的3 - 溴衍生物(6b)。将全硅烷基化的4 - 氯 - 6 - 甲基 - 吡唑并[3,4 - d]嘧啶(7)与四 - O - 乙酰基呋喃核糖(8)进行糖基化反应，得到关键中间体4 - 氯 - 6 - 甲基 - 1 - (2,3,5 - 三 - O - 乙酰基 - β - D - 呋喃核糖基)吡唑并[3,4 - d]嘧啶(9)。9的氨解反应得到4 - 氨基 - 6 - 甲基 - 1 - β - D - 呋喃核糖基吡唑并[3,4 - d]嘧啶(10)，而用氢氧化钠处理得到6 - 甲基别嘌呤醇核糖核苷(11a)。9与硫脲或硒脲反应，随后进行脱乙酰化反应，分别得到6 - 甲基吡唑并[3,4 - d]嘧啶 - 4(5H) - 硫酮核糖核苷(11c)和相应的硒代衍生物(11d)。这些核苷的结构归属是基于光谱研究确定的。这些化合物在体外针对某些病毒和肿瘤细胞进行了测试。除11c外，所有化合物在体外对单纯疱疹病毒2型均表现出显著活性，而1bc对麻疹表现出最强活性且毒性非常低。发现化合物6a、6b和11d在体外是L1210和P388白血病生长的有效抑制剂。
