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吡咯并[3,4-c]吡唑衍生的Aurora激酶抑制剂是具有良好开发前景的新型抗肿瘤药物之一.采用电喷雾-四级杆飞行时间串联质谱技术,对4种吡咯并[3,4-c]吡唑衍生的Aurora激酶抑制剂在电喷雾质谱中的裂解途径及其碎片离子结构进行研究.实验结果表明:吡咯并[3,4-c]吡唑衍生物拥有4个可能的质子化模式,不同的质子化作用会产生不同的碎片离子,且吡咯并[3,4-c]吡唑衍生物N(5)—CO键断裂所产生的碎片离子相对丰度较高,可以作为药物代谢动力学及酶学水平研究中质谱的特征性碎片离子.需要指出的是,化合物3,4能够分别丢失一分子水形成碎片离子[M+H-H2O]+,根据高分辨质谱和理论计算结果我们推测该过程是由质子化作用发生在酰胺氧原子上引发的,而CID条件下N(5)—CO键的进一步断裂可产生相对丰度较高的碎片离子.
Pyrazolo [3,4-c] pyrazole-derived Aurora kinase inhibitors are one of the promising antitumor drugs with good development prospects.Analysis of four kinds of pyrrolo [3] pyrazolones by electrospray-quadrupole time of flight tandem mass spectrometry , 4-c] Pyrazole Derivative Aurora Kinase Inhibitors in Electrospray Ionization Mass Spectrometry and Their Fragment Ion Structures The experimental results show that pyrrolo [3,4-c] pyrazole derivatives have four possible Different protonation results in different fragment ions, and the fragment ions produced by the cleavage of the N (5) -CO bond of pyrrolo [3,4-c] pyrazole derivatives have higher relative abundance, It can be used as a characteristic fragment ion for mass spectrometry in pharmacokinetic and enzymatic studies.It needs to be pointed out that compounds 3,4 can lose one molecule of water respectively to form fragment ions [M + H-H2O] +, and according to high resolution mass spectrometry And theoretical calculation results we speculate that this process is caused by the protonation of amide oxygen atoms induced, and CID conditions N (5) -CO bond further rupture can produce relatively high abundance of fragment ions.