Golankiewicz Bozenna, Ostrowski Tomasz
Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12/14,61-704 Poznan, Poland.
Antiviral Res. 2006 Sep;71(2-3):134-40. doi: 10.1016/j.antiviral.2006.05.004. Epub 2006 May 30.
Tricyclic (T) guanine analogues are a class of compounds in which the N1 and N(2) atoms of the guanine system are linked by etheno bridge to form the 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine system. Almost 70 tricyclic derivatives of guanine-type potent antiherpetic agents acyclovir (ACV), ganciclovir (GCV) and 9-{[cis-1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl}guanine were synthesized and evaluated for activity against viruses of the herpes family. Here, we review the most successful compounds in terms of their antiviral activity and physico-chemical properties. These features are modulated by the kind and position of additional substituents present in the appended third ring of aglycone. The best antiherpetic activity-fluorescence combinations as well as activity of compounds in comparison to parent congeners are summarized. The data presented indicate that compounds of the 6-(4-RPh) family are of particular importance because of their advantageous antiviral potency, increased lipophilicity and good or moderate fluorescence properties.
三环（T）鸟嘌呤类似物是一类化合物，其中鸟嘌呤系统的N1和N(2)原子通过亚乙基桥连接，形成3,9-二氢-9-氧代-5H-咪唑并[1,2-a]嘌呤系统。合成了近70种鸟嘌呤型强效抗疱疹病毒药物阿昔洛韦（ACV）、更昔洛韦（GCV）和9-{[顺式-1',2'-双（羟甲基）环丙-1'-基]甲基}鸟嘌呤的三环衍生物，并评估了它们对疱疹病毒家族病毒的活性。在此，我们根据其抗病毒活性和物理化学性质，对最成功的化合物进行综述。这些特性受苷元附加第三环中存在的其他取代基的种类和位置调节。总结了最佳抗疱疹活性-荧光组合以及与母体同系物相比化合物的活性。所呈现的数据表明，6-(4-RPh)家族的化合物因其有利的抗病毒效力、增加的亲脂性和良好或中等的荧光性质而尤为重要。
