Elliott R D, Pruett P S, Brockman R W, Montgomery J A
J Med Chem. 1987 May;30(5):927-30. doi: 10.1021/jm00388a031.
5'-(Bromoacetamido)-2',5'-dideoxyuridine (3) and derivatives (8, 10, 12, and 14) substituted at the 5-position with bromo, iodo, fluoro, and ethyl groups have been synthesized as potential inhibitors of enzymes that metabolize pyrimidine nucleosides. Also prepared were 2',5'-dideoxyuridine derivatives (4-6) substituted at the 5'-position with 2-bromopropionamido, iodoacetamido, and 4-(fluorosulfonyl)benzamido groups. Compounds 3, 5, 8, 12, and 14 were examined for effect on macromolecular synthesis in L1210 leukemia cells in culture and compared with 5'-(bromoacetamido)-5'-deoxythymidine (1, BAT), a compound with demonstrated cytotoxicity and activity in vivo against P388 murine leukemia. Compounds 3, 8, 12, and 14 inhibited DNA synthesis without significant inhibition of RNA synthesis, and protein synthesis was affected less than DNA synthesis. Compounds 3, 5, 6, 8, 10, 12, and 14 were cytotoxic to H.Ep.-2 and L1210 cells in culture, and 3, 5, 8, and 12 showed activity in the P388 mouse leukemia screen.
5'-(溴乙酰氨基)-2',5'-二脱氧尿苷(3)以及在5-位被溴、碘、氟和乙基取代的衍生物(8、10、12和14)已被合成出来，作为代谢嘧啶核苷的酶的潜在抑制剂。还制备了在5'-位被2-溴丙酰氨基、碘乙酰氨基和4-(氟磺酰基)苯甲酰氨基取代的2',5'-二脱氧尿苷衍生物(4 - 6)。检测了化合物3、5、8、12和14对培养的L1210白血病细胞中大分子合成的影响，并与5'-(溴乙酰氨基)-5'-脱氧胸苷(1，BAT)进行比较，BAT是一种在体内对P388小鼠白血病具有细胞毒性和活性的化合物。化合物3、8、12和14抑制DNA合成，但对RNA合成无明显抑制，蛋白质合成受影响程度小于DNA合成。化合物3、5、6、8、10、12和14对培养的H.Ep.-2和L1210细胞具有细胞毒性，并且3、5、8和12在P388小鼠白血病筛选中显示出活性。
