吡咯并嘧啶类化合物的合成及其抑制JAK3激酶活性的研究  

Synthesis of pyrrolopyrimidines and their JAK3 inhibitory activities

作　　者：支爽[1,2] 杨妙[3] 商倩[4] 陶遵威[1] 刘登科[4] 

机构地区：[1]天津市医药科学研究所,天津300020 [2]天津大学化工学院,天津300072 [3]天津医科大学总医院,天津300052 [4]天津药物研究院,天津300193

出　　处：《现代药物与临床》2017年第4期557-561,共5页Drugs & Clinic

摘　　要：目的设计合成吡咯并嘧啶类化合物并研究其抑制JAK3激酶的活性。方法以4-氯-7H-吡咯并[2,3-d]嘧啶为原料,经过取代、氨基脱保护和N-酰化反应合成两类(Ⅰa和Ⅰb)吡咯并嘧啶类化合物,经体外细胞试验测定其对JAK3激酶的抑制活性。结果设计并合成了8个新化合物,结构经1H-NMR和HR-MS确证。初步活性测试结果显示Ⅰa-1和Ⅰb-3对JAK3的抑制强度与阳性对照药tofacitinib相近。结论目标化合物对JAK3依赖的DAUDI细胞抑制活性较好,对非JAK3依赖的BT-20细胞抑制作用弱。Objective To design and synthesize pyrrolopyrimidines and study their JAK3 inhibitory activities.Methods The two kinds of pyrrolopyrimidines （Ia and Ib）were synthesized from 4-chloro-7H-pyrrolo[2,3-d]pyrimidine via substitution reaction, amino deprotection, and N-acetylation reaction. Their JAK3 inhibitory activities were tested by in vitro cell assay.Results Eight novel compounds were synthesized and their structures were confirmed by 1H-NMR and HR-MS. The in vitro activity experiments showed that compounds Ia-1 and Ib-3 had good inhibition against JAK3, and it was near to control drug tofacitinib.Conclusion Target compounds had good inhibition on JAK3-depended DAUDI cells, and rarely inhibition on non-JAK3-depended BT-20 cells.

关 键 词：JAK3激酶抑制剂 吡咯并嘧啶 合成 

分 类 号：R914[医药卫生—药物化学]