McGuigan Christopher, Blewett Sally, Siccardi Dario, Erichsen Jonathan T, Andrei Graciela, Snoek Robert, De Clercq Erik, Balzarini Jan
Welsh School of Pharmacy, Cardiff University, UK.
Antivir Chem Chemother. 2002 Mar;13(2):91-9. doi: 10.1177/095632020201300203.
We have previously reported bicyclic furanopyrimidines as potent and selective inhibitors of varicella zoster virus (VZV) with subnanomolar activity for p-alkylphenyl substituted analogues. These compounds are highly lipophilic and of limited water solubility. In an effort to address this issue, and with a view to oral dosing, we have sought to enhance water solubility whilst retaining high antiviral potency and we herein report a novel series of p-alkyloxyphenyl compounds which contain a phenolic ether atom intended to boost hydrophilicity. We report the synthesis, characterisation and antiviral evaluation of this series and note the retention of extremely high antiviral potency, with EC50 values as low as 1 nanomolar.
我们之前曾报道过双环呋喃嘧啶作为水痘带状疱疹病毒（VZV）的强效和选择性抑制剂，对对烷基苯基取代类似物具有亚纳摩尔活性。这些化合物具有高度脂溶性且水溶性有限。为了解决这个问题，并考虑到口服给药，我们试图提高水溶性，同时保持高抗病毒效力，在此我们报告了一系列新型的对烷氧基苯基化合物，它们含有一个酚醚原子以增强亲水性。我们报告了该系列化合物的合成、表征和抗病毒评估，并注意到其保留了极高的抗病毒效力，EC50值低至1纳摩尔。
