氯吡格雷类似物的合成及其抗血小板聚集活性

Synthesis of Clopidogrel Analogues and Their Anti-platelet Aggregation Activities

α-溴代邻氯苯乙酸经酯化反应后再与4,5,6,7-四氢噻吩并[3,2-c]吡啶发生取代反应合成氯吡格雷类似物(4b^4e);2-(2-氯苯基)-2-(4,5,6,7-四氢噻吩并[3,2-c]吡啶-5-基)乙酸(4a)经酯化反应合成4f^4k;4f与AgNO3反应制得4l;4a经酰胺化制得另外两个氯吡格雷类似物(5c和5m)。4和5的其结构经1HNMR,IR和MS表征。初步生物活性测试结果表明:4和5均有一定的抗血小板聚集作用,其中4g和4b尤其突出,对大鼠血小板聚集的抑制百分率分别为46.1%和38.2%。

Clopidogrel analogues（4b^4e） were synthesized by esterification of α-bromo-o-chlorophenylacetic acid with ROH,and then substitution reaction with 4,5,6,7-tetrahydro-thienopyridyl.4f^4k were synthesized by esterification of α-（4,5,6,7-tetrahydro-thieno-5-pyridyl）-2-chlorophenylacetic acid（4a） with ROH.4f reacted with AgNO3 to give 4l.Another clopidogrel analogues（5c,5m） were prepared by amidation of 4a with RNH2.The structures of 4 and 5 were characterized by 1H NMR,IR and MS.The biological actiyity tests showed that all of 4 and 5 exhibited significant anti-platelet aggregation.For anti-platelet aggregation of rats,the inhibition rate of 4g and 4b were 46.1% and 38.2%,respectively.