阿哌沙班衍生物的合成及Ⅹa因子抑制活性  

Synthesis and factor Xa inhibitory activity of apixaban derivatives

作　　者：邢峻豪 张媛[1] 胡晓雯[2] 周金培[1] 张惠斌[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009 [2]南京医科大学基础医学院,南京210029

出　　处：《中国药科大学学报》2013年第4期289-295,共7页Journal of China Pharmaceutical University

基　　金：国家"重大新药创制"科技重大专项资助项目(No.2013ZX09301303-002);江苏省产学研联合创新资金-前瞻性联合研究项目资助(No.BY2011158);中央高校基本科研业务费专项基金资助项目(No.JKY2011092)~~

摘　　要：在阿哌沙班的结构基础上,保持其P1部分不变,对其P4部分进行结构改造,用一系列芳香酰胺基团代替2-氮己酮,合成了一系列未见报道的吡唑并吡啶酮类化合物。所合成化合物结构均经IR,1H NMR和MS确证,并对这些化合物的Ⅹa因子抑制活性进行了测定,结果表明所有化合物均表现出一定的Ⅹa因子抑制活性,但活性均低于阳性药阿哌沙班。Based on the current structure-activity relationship of apixaban,keeping P1 portions unchanged and replace δ-valerolactam in P4 portions with aromatic amide group,a series of dihydropyrazolopyridinones not reported were designed and synthesized.The structures of all the synthesized derivatives were identified by IR,1H NMR and MS.And then their anti-factor Xa activity was tested.The results showed that all the tested compounds exhibited factor Xa inhibitory activity,but with less potency than that of apixaban.

关 键 词：阿哌沙班 衍生物 合成 Ⅹa因子抑制剂 

分 类 号：R914.5[医药卫生—药物化学]