依布硒啉衍生物对白三烯B_4生物合成抑制作用及其构效关系  

INHIBITORY EFFECT AND STRUCTURE ACTIVITY RELATIONSHIP OF EBSELEN DERIVATIVES ON LEUKOTRIENE B 4 BIOSYNTHESIS

作　　者：郭颖[1] 肖颖歆[1] 郭宗儒[1] 程桂芳[1] 

机构地区：[1]中国医学科学院,中国协和医科大学药物研究所,北京100050

出　　处：《药学学报》1999年第9期652-654,共3页Acta Pharmaceutica Sinica

基　　金：国家医药局新药基金

摘　　要：目的：研究一系列依布硒啉衍生物对白三烯 Ｂ４ 生物合成的影响，并探讨其构效关系。方法：高效液相色谱法测定白三烯 Ｂ４ 。结果：依布硒啉的磺酰胺类似物以及 Ｎ芳香环取代的磺酰胺衍生物对白三烯 Ｂ４ 生物合成具有抑制作用，其 Ｉ Ｃ５ ０ 在１０ － ５ ～１０ － ６ ｍｏｌ· Ｌ－ １ 之间，并存在一定的构效关系。结论：磺酰胺基团上的酸性氢原子是关键因素，它的存在可以形成分子内氢键，从而使化合物具有活性。AIM: A series of ebselen derivatives were synthesized for studying their effects on LTB 4 biosynthesis. Preliminary analysis of structure activity relationship(SAR) of these compounds were conducted. METHODS: High performance liquid chromatography(HPLC) was used to determine LTB 4. RESULTS: Sulfonamide analogues of ebselen and N aryl substituted derivatives of ebselen showed significant inhibitory effects on LTB 4 biosynthesis with IC 50 of 10 -5 mol·L -1 to 10 -6 mol·L -1 .CONCLUSION: According to SAR, the presence of an acidic hydrogen atom on the sulfonamido group seemed to be a critical factor for the activity. In the absence of the hydrogen or loss of the ability to form intermolecular hydrogen bonding compounds would abolish the activity.

关 键 词：白三烯B4 生物合成 有机硒化合物 依布硒啉 

分 类 号：R971.1[医药卫生—药品] R914.5[医药卫生—药学]