Orr G F, Musso D L, Kelley J L, Joyner S S, Davis S T, Baccanari D P
Division of Organic Chemistry, Glaxo Wellcome Inc., Research Triangle Park, North Carolina 27709, USA.
J Med Chem. 1997 Apr 11;40(8):1179-85. doi: 10.1021/jm960688j.
Structure-activity relationship studies on a series of 1-((2-hydroxyethoxy)methyl)-5-(3-(substituted-phenoxy)benzyl)uracils as inhibitors of murine liver uridine phosphorylase have led to compounds with IC50s as low as 1.4 nM. The two most potent compounds, 10j (3-cyanophenoxy) and 11f (3-chlorophenoxy) were tested in vivo for effects on steady-state concentrations of circulating uridine in mice and rats. Both compounds were substantially more efficacious than BAU (5-benzylacyclouridine) both in vitro and in vivo.
对一系列1-((2-羟基乙氧基)甲基)-5-(3-(取代苯氧基)苄基)尿嘧啶作为小鼠肝脏尿苷磷酸化酶抑制剂的构效关系研究已得到IC50低至1.4 nM的化合物。两种最有效的化合物，10j（3-氰基苯氧基）和11f（3-氯苯氧基），在体内测试了对小鼠和大鼠循环尿苷稳态浓度的影响。这两种化合物在体外和体内均比BAU（5-苄基阿糖脲苷）有效得多。
