Synthesis and antiviral properties of (+/-)-5'-noraristeromycin and related purine carbocyclic nucleosides. A new lead for anti-human cytomegalovirus agent design.
Synthesis and antiviral properties of (+/-)-5'-noraristeromycin and related purine carbocyclic nucleosides. A new lead for anti-human cytomegalovirus agent design.
复制标题
(l-)-5-去甲雷斯特霉素和相关嘌呤碳环核苷的合成和抗病毒特性。
DOI：
10.1021/jm00096a012
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发表时间：
1992
影响因子：
7.3
通讯作者：
DeClercq,E
中科院分区：
文献类型：
--
作者：
Patil,SD;Schneller,SW;Hosoya,M;Snoeck,R;Andrei,G;Balzarini,J;DeClercq,E
从（±）-(la, 2/3, 3/ 3,4 <*)-4-氨基- 1,2,3 -环戊三醇(7)的2,3 - o-异丙基衍生物开始，分三步制备（±）-5'-去甲马霉素(3)。同样的原料还制备了相关的次黄嘌呤(4)、鸟嘌呤(5)和2,6 -二氨基嘌呤(6)类似物。化合物3 ~ 6对多种病毒的抗病毒活性进行了评价，其中3对牛痘病毒、人巨细胞病毒、水疱性口炎病毒、副流感（3型）病毒、麻疹病毒、呼吸道合胞病毒、呼肠孤病毒（1型）和沙粒病毒Junin和Tacaribe有显著的抗病毒活性。这些化合物对抗病毒研究中使用的宿主细胞单层均无细胞毒性。3和6都被发现是s -腺苷- l-同型半胱氨酸水解酶（AdoHcy水解酶）的抑制剂，这可能是它们抗病毒活性的原因。抑制adhcy水解酶是人类巨细胞病毒药物设计的新途径。此外，在治疗痘病毒、横纹肌病毒、副腮腺炎病毒、reo病毒和沙粒病毒感染时，应进一步研究3的活性。
(±)-5'-Noraristeromycin (3) has been prepared in three steps beginning with the 2, 3-O-isopropylidene derivative of (±)-(la, 2/3, 3/3, 4<*)-4-amino-1, 2, 3-cyclopentanetriol (7). Also prepared from the same starting material were the related hypoxanthine (4), guanine (5), and 2, 6-diaminopurine (6) analogues. Compounds 3-6 were evaluated for antiviral activity against a large number of viruses with marked activity being observed for 3 towards vaccinia virus, human cytomegalovirus, vesicular stomatitis virus, parainfluenza (type 3) virus, measles virus, respiratory syncytial virus, reovirus (type 1), andthe arenaviruses Junin and Tacaribe. None of the compounds showed cytotoxicity to the host cell monolayers used in the antiviral studies. Both 3 and 6 have been found to be inhibitors of S-adenosyl-L-homocysteine hydrolase (AdoHcy hydrolase), which likely accounts for their antiviral activity. Inhibition of AdoHcy hydrolase represents a new approach to human cytomegalovirus drug design that should be pursued. Also, the activity of 3 should be further scrutinized for the treatment of pox-, rhabdo-, paramyxo-, reo-, and arenavirus infections.