Saxena N K, Coleman L A, Drach J C, Townsend L B
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
J Med Chem. 1990 Jul;33(7):1980-3. doi: 10.1021/jm00169a027.
The sodium salt of 4-amino-3-cyanopyrazolo[3,4-d]pyrimidine (1) was condensed with (2-acetoxyethoxy)methyl bromide (2) to provide the corresponding protected acyclic nucleoside, 4-amino-3-cyano-1-[(2-acetoxyethoxy)methyl]-pyrazolo[3,4-d]pyrimid ine (3). Treatment of 3 with sodium methoxide in methanol provided a good yield of methyl 4-amino-1-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine-3- formimidate (4). Treatment of the imidate (4) with sodium hydrogen sulfide gave the thiocarboxamide derivative 5. Aqueous base transformed 4 into 4-amino-1-[(2-hydroxyethoxy)methyl]pyrazolo[3,4-d]pyrimidine-3- carboxamide (6) in good yield. Treatment of 5 with mercuric chloride furnished the toyocamycin analogue 7. Evaluation of compounds 1, 3-7 revealed that only the heterocycle (1) and the thiocarboxamide acyclic nucleoside (5) were active. Compound 5 was the more potent with activity against human cytomegalovirus and herpes simplex virus type 1.
4-氨基-3-氰基吡唑并[3,4-d]嘧啶（1）的钠盐与（2-乙酰氧基乙氧基）甲基溴（2）缩合，得到相应的保护的无环核苷，4-氨基-3-氰基-1-[(2-乙酰氧基乙氧基)甲基]吡唑并[3,4-d]嘧啶（3）。在甲醇中用甲醇钠处理3，以良好的产率得到4-氨基-1-[(2-羟基乙氧基)甲基]吡唑并[3,4-d]嘧啶-3-甲脒（4）。用硫化氢钠处理亚胺酸酯（4）得到硫代甲酰胺衍生物5。在水碱作用下，4以良好的产率转化为4-氨基-1-[(2-羟基乙氧基)甲基]吡唑并[3,4-d]嘧啶-3-甲酰胺（6）。用氯化汞处理5得到丰加霉素类似物7。对化合物1、3 - 7的评估表明，只有杂环（1）和硫代甲酰胺无环核苷（5）具有活性。化合物5对人巨细胞病毒和1型单纯疱疹病毒的活性更强。
