Beauchamp L M, Serling B L, Kelsey J E, Biron K K, Collins P, Selway J, Lin J C, Schaeffer H J
Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
J Med Chem. 1988 Jan;31(1):144-9. doi: 10.1021/jm00396a021.
A series of pyrimidines related to the potent antiherpetic agent 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (1, BW B759U), all containing the same acyclic chain, have been synthesized. Some of the compounds were derivatives of the naturally occurring bases, cytosine, uracil, and thymine; others included compounds in which the 5-position of the cytosine and uracil moieties were substituted by bromo, iodo, fluoro, methyl, and amino groups. Other variations of the cytosine derivatives were the 5-aza, 2-mercapto, 4-methylamino, 4-dimethylamino, and isocytosine congeners. A 4-aminopyrimidine adduct was also made. Antiviral testing showed that 1-[(1,3-dihydroxy-2-propoxy)methyl]cytosine (18, BW A1117U) was equivalent to the guanine analogue in potency against human cytomegalovirus and Epstein Barr virus. Other compounds in the series were largely inactive in antiviral screening against the herpesviruses.
已经合成了一系列与强效抗疱疹剂9-[(1,3-二羟基-2-丙氧基)甲基]鸟嘌呤（1，BW B759U）相关的嘧啶，它们都含有相同的无环链。其中一些化合物是天然存在的碱基胞嘧啶、尿嘧啶和胸腺嘧啶的衍生物；其他化合物包括胞嘧啶和尿嘧啶部分的5位被溴、碘、氟、甲基和氨基取代的化合物。胞嘧啶衍生物的其他变体包括5-氮杂、2-巯基、4-甲基氨基、4-二甲基氨基和异胞嘧啶类似物。还制备了一种4-氨基嘧啶加合物。抗病毒测试表明，1-[(1,3-二羟基-2-丙氧基)甲基]胞嘧啶（18，BW A1117U）在抗人巨细胞病毒和爱泼斯坦-巴尔病毒的效力上与鸟嘌呤类似物相当。该系列中的其他化合物在针对疱疹病毒的抗病毒筛选中大多无活性。
