申请人:Ortho Pharmaceutical Corporation
公开号:US05464865A1
公开(公告)日:1995-11-07
The invention provides novel 5-hydroxy-4-aryl- and 5-hydroxy-4-(arylthio)-2(5H)-furanones of the following structure: ##STR1## wherein R contains from about five to about twenty carbon atoms and is defined herein; X is oxygen, sulfur, SO.sub.2, NH, N(lower alkyl), N(lower acyl), aminocarbonyl, carbonyl, carbonylamino, CH.sub.2 or a carbon-carbon bond; Y is hydrogen, halogen, lower alkyl, nitro, alkylthio, perfluoroalkyl, hydroxy, or lower alkoxy(C.sub.1 -C.sub.8); Z is sulfur or a carbon-carbon bond; and Q is H, an alkyl of from 1-20 carbon atoms, COR', COOR', CONHR', PO(OR')2, PO(OR')R" wherein R' and R" are independently selected from the group consisting of H, an alkyl of from 1-20 carbon atoms, phenyl, and substituted phenyl and prodrugs thereof and pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprising these compounds, methods of using these compounds as inhibitors of inflammation and for treating other diseases characterized by the overproduction of arachidonic acid metabolites, intermediates and methods of preparing these compounds are also provided.
本发明提供了以下结构的新型5-羟基-4-芳基-和5-羟基-4-(芳
硫基)-
2(5H)-呋喃酮:其中R含有约五至约二十个
碳原子并在此处定义;X是
氧、
硫、SO.sub.2、NH、N(较低烷基)、N(较低酰基)、
氨基甲酰、甲酰、甲酰
氨基、CH.sub.2或
碳-
碳键;Y是
氢、卤素、较低烷基、硝基、烷基
硫、
全氟烷基、羟基或较低烷
氧基(C.sub.1 -C.sub.8);Z是
硫或
碳-
碳键;Q是H、由1-20个
碳原子组成的烷基、COR'、COOR'、CONHR'、PO(OR')2、PO(OR')R",其中R'和R"分别独立选择自H、由1-20个
碳原子组成的烷基、
苯基和取代
苯基及其前药和其药用盐。还提供了包含这些化合物的制药组合物,使用这些化合物作为炎症
抑制剂和用于治疗由
花生四烯酸代谢产物过度产生所表征的其他疾病的方法,以及制备这些化合物的
中间体和方法。