Bobek M, Kavai I, Sharma R A, Grill S, Dutschman G, Cheng Y C
Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.
J Med Chem. 1987 Nov;30(11):2154-7. doi: 10.1021/jm00394a039.
5-Ethynyl-1-beta-D-arabinofuranosylcytosine (EAC) was prepared from 1-(2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)cytosine by iodination followed by coupling with (trimethylsilyl)acetylene and deblocking. At 50 microM, EAC was found to inhibit the in vitro replication of herpes simplex virus type 1 and type 2 by greater than 99%. EAC also showed activity against a strain of HSV-1 resistant to (E)-5-(2-bromovinyl)-2'-deoxyuridine which has an alteration of the virus-induced thymidine kinase (TK). At 100 microM, EAC did not inhibit the in vitro growth of leukemia L1210 and HeLa cells. EAC was resistant to the action of dCR-CR deaminase, its rate of deamination being approximately 2% that of dCR. The compound was a poor substrate for dCR kinase, but it was phosphorylated by HSV-1- and HSV-2-induced TKs at 50% and 30%, respectively, the rate of thymidine.
5-乙炔基-1-β-D-阿拉伯呋喃糖基胞嘧啶（EAC）由1-(2,3,5-三-O-乙酰基-β-D-阿拉伯呋喃糖基)胞嘧啶经碘化、与(三甲基硅基)乙炔偶联及脱保护制备而成。在50微摩尔浓度下，发现EAC对1型和2型单纯疱疹病毒的体外复制抑制率超过99%。EAC对一株对（E）-5-（2-溴乙烯基）-2'-脱氧尿苷耐药的HSV-1毒株也有活性，该毒株的病毒诱导胸苷激酶（TK）发生了改变。在100微摩尔浓度下，EAC不抑制白血病L1210细胞和HeLa细胞的体外生长。EAC对dCR-CR脱氨酶的作用具有抗性，其脱氨速率约为dCR的2%。该化合物是dCR激酶的不良底物，但分别被HSV-1和HSV-2诱导的TK磷酸化，磷酸化率分别为50%和30%，与胸苷的速率相同。
