(+-)-carbocyclic 5'-nor-2'-deoxyguanosine and related purine derivatives: synthesis and antiviral properties.
(+-)-carbocyclic 5'-nor-2'-deoxyguanosine and related purine derivatives: synthesis and antiviral properties.
复制标题
(-)-碳环 5-nor-2-脱氧鸟苷和相关嘌呤衍生物：合成和抗病毒特性。
DOI：
10.1021/jm00090a007
复制
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;Koga,M;Schneller,SW;Snoeck,R;DeClercq,E
从3-环戊烯-1-基胺盐酸盐开始，制备了碳环2'-脱氧鸟苷(2)、2'-脱氧腺苷(3)和2, 6-二氨基嘌呤2'-脱氧呋喃核苷(4)的5'-去甲衍生物。评估了这些化合物相对于单纯疱疹病毒、水痘带状疱疹病毒、巨细胞病毒、牛痘病毒、水泡性口炎病毒和人类免疫缺陷病毒的抗病毒潜力，发现缺乏活性。此外，化合物 2-4 对宿主（人二倍体成纤维细胞 ESM 和 HEL）细胞几乎无毒。这些生物学特性可能是由于 2-4 无法磷酸化至所需的核苷酸水平，而该水平可能是生物活性所必需的，与碳环 2'-脱氧鸟苷 (1) 相关，碳环 2'-脱氧鸟苷 (1) 因转化为其 5'-三磷酸衍生物而具有显着的抗病毒特性。Racemic1 和 D-碳环 2,-脱氧鸟苷（表示为 1）因此显示出显着的抗病毒活性选择性转化为其S'-三磷酸衍生物。 3 最近的研究4"" 3 重点关注缺乏 C-5' 碳的核苷衍生的抗病毒药物的开发，促进了 (±)-2 作为 1 的 5'-去甲衍生物的合成和评估。本报告介绍了这项研究的结果，其中还包括腺嘌呤 (3) 9 和 2, 6-二氨基嘌呤 (4) 衍生物。
Beginning with 3-cyclopenten-l-ylaminehydrochloride, the 5'-nor derivatives of carbocyclic 2'-deoxyguanosine (2), 2'-deoxyadenosine (3), and 2, 6-diaminopurine 2'-deoxyribofuranoside (4) have been prepared. These compounds were evaluated for antiviral potential versus herpes simplex virus, varicella-zoster virus, cytomegalovirus, vaccinia virus, vesicular stomatitis virus, and human immunodeficiency virus and found to lack activity. Also, compounds 2-4 were virtually nontoxic towardthe host (human diploid fibroblast ESM and HEL) cells. These biologicalproperties may be dueto the inability of 2-4 to be phosphorylated to the requisite nucleotide level that is likely to be necessary for biological activity by correlation to carbocyclic 2'-deoxyguanoeine (1), which possesses significant antiviral properties as a result of conversion to its 5'-triphosphate derivative.Racemic1 and D-carbocyclic2 2,-deoxyguanosine (represented as 1) have shown significant antiviral activity as a result of selective conversion to their S'-triphosphate de-rivatives. 3 Recent studies4"" 3 focusing on the development of antiviral agents derived from nucleosides lacking the C-5'carbon prompted a synthesis and evaluation of (±)-2 as the 5'-nor derivative of 1. The results of this investigation, which also included the adenine (3) 9 and 2, 6-di-aminopurine (4) derivatives, are presented in this report.