在胸腺嘧啶的(,)-3-羟基-2-(膦酰甲氧基)丙基(HPMP)衍生物的2位引入氰基可引发选择性抗乙肝病毒活性。
Introduction of a cyano group at the 2-position of an (,)-3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) derivative of thymine elicits selective anti-HBV activity.
作者信息
Tan Shuai, Groaz Elisabetta, Prichard Mark N, Kalkeri Raj, Ptak Roger, Herdewijn Piet
机构信息
KU Leuven, Rega Institute for Medical Research, Medicinal Chemistry Herestraat 49-Box 1041 3000 Leuven Belgium
Department of Pharmaceutical and Pharmacological Sciences, University of Padova Via Marzolo 5 35131 Padova Italy.
出版信息
RSC Med Chem. 2021 Apr 29;12(5):804-808. doi: 10.1039/d1md00086a. eCollection 2021 May 26.
Abstract
The substantial impact of acyclic nucleoside phosphonates (ANPs) on human medicine encourages the synthesis of new ANP analogues with a potentially differentiated antiviral spectrum. Herein, we demonstrate the functionalization of the 2-position of the (,)-3-hydroxy-2-(phosphonomethoxy)propyl side-chain of an inactive ANP with a polar cyano group to generate a thymine analogue with selective inhibition of hepatitis B virus (HBV) replication (SI > 302; EC = 0.33 μM), without significant antiretroviral activity. These findings suggest new strategies to synthesize unique ANPs with a targeted antiviral profile.
摘要
无环核苷膦酸酯（ANPs）对人类医学的重大影响促使人们合成具有潜在不同抗病毒谱的新型ANP类似物。在此，我们展示了用极性氰基对一种无活性ANP的（±）-3-羟基-2-（膦酰甲氧基）丙基侧链的2-位进行官能化，以生成一种对乙型肝炎病毒（HBV）复制具有选择性抑制作用的胸腺嘧啶类似物（SI>302；EC = 0.33μM），且无显著抗逆转录病毒活性。这些发现为合成具有靶向抗病毒特性的独特ANPs提供了新策略。
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