Petrie C R, Cottam H B, McKernan P A, Robins R K, Revankar G R
J Med Chem. 1985 Aug;28(8):1010-6. doi: 10.1021/jm00146a007.
Several 3,4,6-trisubstituted pyrazolo[3,4-d]pyrimidine ribonucleosides were prepared and tested for their biological activity. High-temperature glycosylation of 3,6-dibromoallopurinol with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of BF3 X OEt2, followed by ammonolysis, provided 6-amino-3-bromo-1-beta-D-ribofuranosylpyrazolo-[3,4-d]pyrimidin-4(5H)-on e. Similar glycosylation of either 3-bromo-4(5H)-oxopyrazolo [3,4-d]pyrimidin-6-yl methyl sulfoxide or 6-amino-3-bromopyrazolo [3,4-d]pyrimidin-4(5H)-one, and subsequent ammonolysis, also gave 7a. The structural assignment of 7a was on the basis of spectral studies, as well as its conversion to the reported guanosine analogue 1d. Application of this glycosylation procedure to 6-(methylthio)-4(5H)-oxopyrazolo[3,4-d]pyrimidine-3-carboxamide gave the corresponding N-1 glycosyl derivative. Dethiation and debenzoylation of 16a provided an alternate route to the recently reported 3-carbamoylallopurinol ribonucleoside thus confirming the structural assignment of 16a and the nucleosides derived therefrom. Oxidation of 16a and subsequent ammonolysis afforded 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]pyrimidine-3-carboxamide. Alkaline treatment of 15a gave 6-azacadeguomycin. Acetylation of 15a, followed by dehydration with phosgene, provided the versatile intermediate 6-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-4(5H)-oxopyrazolo [3, 4-d]pyrimidine-3-carbonitrile. Deacetylation of 19 gave 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]pyrimidine-3-carbonitrile. Reaction of 19 with H2S gave 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]pyrimidine-3-thiocarboxamide. All of these compounds were tested in vitro against certain viruses and tumor cells. Among these compounds, the guanosine analogues 7a and 20a showed significant activity against measles in vitro and were found to exhibit moderate antitumor activity in vitro against L1210 and P388 leukemia. 6-Azacadeguomycin and all other compounds were inactive against the viruses and tumor cells tested in vitro.
制备了几种3,4,6-三取代的吡唑并[3,4-d]嘧啶核糖核苷，并对其生物活性进行了测试。在三氟化硼乙醚络合物存在下，3,6-二溴别嘌呤醇与1-O-乙酰基-2,3,5-三-O-苯甲酰基-D-呋喃核糖进行高温糖基化反应，随后进行氨解反应，得到6-氨基-3-溴-1-β-D-呋喃核糖基吡唑并[3,4-d]嘧啶-4(5H)-酮。3-溴-4(5H)-氧代吡唑并[3,4-d]嘧啶-6-基甲基亚砜或6-氨基-3-溴吡唑并[3,4-d]嘧啶-4(5H)-酮进行类似的糖基化反应，随后进行氨解反应，也得到了7a。7a的结构归属基于光谱研究以及其转化为报道的鸟苷类似物1d。将这种糖基化方法应用于6-(甲硫基)-4(5H)-氧代吡唑并[3,4-d]嘧啶-3-甲酰胺，得到了相应的N-1糖基衍生物。16a的脱硫和脱苯甲酰基反应提供了一条通往最近报道的3-氨甲酰基别嘌呤醇核糖核苷的替代路线，从而证实了16a及其衍生核苷的结构归属。16a的氧化反应及随后的氨解反应得到6-氨基-1-β-D-呋喃核糖基-4(5H)-氧代吡唑并[3,4-d]嘧啶-3-甲酰胺。15a经碱性处理得到6-氮杂卡德古霉素。15a乙酰化后，用光气脱水，得到通用中间体6-氨基-1-(2,3,5-三-O-乙酰基-β-D-呋喃核糖基)-4(5H)-氧代吡唑并[3,4-d]嘧啶-3-腈。19脱乙酰基得到6-氨基-1-β-D-呋喃核糖基-4(5H)-氧代吡唑并[3,4-d]嘧啶-3-腈。19与硫化氢反应得到6-氨基-1-β-D-呋喃核糖基-4(5H)-氧代吡唑并[3,4-d]嘧啶-3-硫代甲酰胺。所有这些化合物都在体外针对某些病毒和肿瘤细胞进行了测试。在这些化合物中，鸟苷类似物7a和20a在体外对麻疹显示出显著活性，并且发现在体外对L1210和P388白血病具有中等抗肿瘤活性。6-氮杂卡德古霉素和所有其他化合物在体外对所测试的病毒和肿瘤细胞均无活性。
