Hong C I, De N C, Tritsch G L, Chheda G B
J Med Chem. 1976 Apr;19(4):555-8. doi: 10.1021/jm00226a024.
Syntheses and biological activities of 26 N4-substituted 4-aminopyrazolo[3,4-d]pyrimidines as analogs of naturally occurring modified nucleic acid bases, N-(purin-6-ylcarbamoyl)-L-threonine and N6-(delta2-isopentenyl)adenine, are described. 4-Aminopyrazolo[3,4-d]pyrimidine was converted into the desired intermediate, ethyl pyrazolo[3,4-d]pyrimidine-4-carbamate (2). 4-Ureidopyrazolo[3,4-d]pyrimidines (6-26) were prepared by displacement of the ethoxy group of the carbamate 2 by amino acids and a variety of amines and by a reaction of 4-aminopyrazolo[3,4-d]pyrimidine (1) with isocyanates. N4-Alkylaminopyrazolo[3,4-d]pyrimidines were generally prepared by displacement of the chlorine from 4-chloropyrazolo[3,4-d]pyrimidine with various amines. Several analogs exhibited moderate to very good growth inhibitory activities against cultured L1210 leukemia and 6410 human leukemic myeloblasts.
描述了26种N4-取代的4-氨基吡唑并[3,4-d]嘧啶作为天然存在的修饰核酸碱基N-(嘌呤-6-基氨基甲酰基)-L-苏氨酸和N6-(δ2-异戊烯基)腺嘌呤类似物的合成及其生物活性。4-氨基吡唑并[3,4-d]嘧啶转化为所需的中间体吡唑并[3,4-d]嘧啶-4-氨基甲酸乙酯(2)。4-脲基吡唑并[3,4-d]嘧啶(6-26)通过用氨基酸和各种胺取代氨基甲酸酯2的乙氧基以及通过4-氨基吡唑并[3,4-d]嘧啶(1)与异氰酸酯反应制备。N4-烷基氨基吡唑并[3,4-d]嘧啶通常通过用各种胺取代4-氯吡唑并[3,4-d]嘧啶中的氯来制备。几种类似物对培养的L1210白血病细胞和6410人白血病髓母细胞表现出中等至非常好的生长抑制活性。
