Synthesis and biological evaluation of acyclic neplanocin analogues.
Synthesis and biological evaluation of acyclic neplanocin analogues.
复制标题
无环奈普拉诺星类似物的合成和生物学评价。
DOI：
10.1021/jm00384a033
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发表时间：
1987
影响因子：
7.3
通讯作者：
Vince,R
中科院分区：
文献类型：
--
作者：
Hua,M;Korkowski,PM;Vince,R
通过腺嘌呤或N，N-乙酰基鸟嘌呤与（E）-1，4-二氯丁-2-烯缩合并随后水解来制备无环奈普拉诺星类似物。以腺嘌呤为起始嘌呤，得到N-9-取代的产物9-[（E）-4-羟基丁-2-烯基]腺嘌呤（5），而N，N-乙酰基鸟嘌呤得到N-7和N-9异构体。细胞培养研究表明，只有氯取代的中间体9-[（E）-4-氯丁-2-烯基]腺嘌呤（4）对P-388小鼠淋巴白血病细胞表现出显著的细胞毒性，而N-9-取代的鸟嘌呤类似物9-[（E）-4-羟基丁-2-烯基]鸟嘌呤（10）抑制单纯疱疹病毒1型和2型的复制。
Acyclic neplanocin analogues were prepared by condensation of adenine or JV^-acetylguanine with (E)-l, 4-di-chlorobut-2-ene and subsequent hydrolysis. The N-9-substituted product 9-[(E)-4-hydroxybut-2-enyl] adenine (5) was obtained when adenine was employed as the starting purine, while A^-acetylguanine yielded both the N-7 and N-9 isomers. Cell-culture studies revealed that only the chloro-substituted intermediate 9-[(E)-4-chlorobut-2-enyl] adenine (4) exhibited significant cytotoxicity againstP-388 mouse lymphoid leukemia cells, while the N-9-substituted guanine analogue 9-[(E)-4-hydroxybut-2-enyl] guanine (10) inhibited replication of herpes simplex viruses type 1 and type 2.