Bhat G A, Montero J L, Panzica R P, Wotring L L, Townsend L B
J Med Chem. 1981 Oct;24(10):1165-72. doi: 10.1021/jm00142a009.
The chemical synthesis of certain 4-substituted pyrazolo[3,4-d]pyrimidine nucleosides is described. Using 1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4-one (1) as the starting material, the reactive intermediate 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (2) was prepared in excellent yield. Compound 2 served as a versatile precursor for the synthesis of a number of 4-substituted pyrazolo[3,4-d]pyrimidine nucleosides. In antitumor studies of these nucleosides, in vitro and in vivo, it was found that any alteration of the 4-amino substituent of 4-amino-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidine (3) was accompanied by a significant decrease or loss of antitumor activity. On the other hand, introduction of certain substituents at the 3 position of 3 (synthesis reported previously) led to a dramatic increase in antitumor activity in comparison to the parent compound.
描述了某些4-取代的吡唑并[3,4-d]嘧啶核苷的化学合成。以1-(2,3,5-三-O-乙酰基-β-D-呋喃核糖基)吡唑并[3,4-d]嘧啶-4-酮(1)为起始原料，以优异的产率制备了反应中间体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(2)。化合物2是合成多种4-取代的吡唑并[3,4-d]嘧啶核苷的通用前体。在这些核苷的抗肿瘤研究中，在体外和体内发现，4-氨基-1-β-D-呋喃核糖基吡唑并[3,4-d]嘧啶(3)的4-氨基取代基的任何改变都伴随着抗肿瘤活性的显著降低或丧失。另一方面，与母体化合物相比，在3的3位引入某些取代基导致抗肿瘤活性急剧增加。
