Van Draanen N A, Freeman G A, Short S A, Harvey R, Jansen R, Szczech G, Koszalka G W
Division of Experimental Therapy, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709, USA.
J Med Chem. 1996 Jan 19;39(2):538-42. doi: 10.1021/jm950701k.
A series of 2'-deoxy-4'-thioribo purine nucleosides was prepared by trans-N-deoxyribosylase-catalyzed reaction of 2'-deoxy-4'-thiouridine with a variety of purine bases. This synthetic procedure is an improvement over methods previously used to prepare purine 4'-thio nucleosides. The compounds were tested against hepatitis B virus (HBV), human cytomegalovirus (HCMV), herpes simplex virus (HSV-1 and HSV-2), varicella zoster virus (VZV), and human immunodeficiency virus (HIV-1). Cytotoxicity was determined in a number of cell lines. Several compounds were extremely potent against HBV and HCMV and had moderate to severe cytotoxicity in vitro. The lead compound from the series, 2-amino-6-(cyclopropylamino)purine 2'-deoxy-4'-thioriboside, was the most potent and selective agent against HCMV and HBV replication in vitro; however, this analogue was nephrotoxic when tested in vivo.
通过反式-N-脱氧核糖基酶催化2'-脱氧-4'-硫代尿苷与多种嘌呤碱的反应，制备了一系列2'-脱氧-4'-硫代核糖嘌呤核苷。该合成方法是对先前用于制备嘌呤4'-硫代核苷的方法的改进。对这些化合物针对乙型肝炎病毒（HBV）、人巨细胞病毒（HCMV）、单纯疱疹病毒（HSV-1和HSV-2）、水痘带状疱疹病毒（VZV）和人类免疫缺陷病毒（HIV-1）进行了测试。在多种细胞系中测定了细胞毒性。几种化合物对HBV和HCMV具有极强的活性，并且在体外具有中度至重度细胞毒性。该系列中的先导化合物2-氨基-6-（环丙基氨基）嘌呤2'-脱氧-4'-硫代核糖苷是体外针对HCMV和HBV复制最有效和最具选择性的药物；然而，该类似物在体内测试时具有肾毒性。
