3-aminopyrazolopyrazine derivatives as spleen tyrosine kinase inhibitors.
Spleen tyrosine kinase is a new promising target for drug discovery to treat human cancer and inflammatory disorders. A series of pyrazolopyrazine-3-amine and pyrazolopyrimidine-3-amine derivatives was designed and synthesized as new spleen tyrosine kinase inhibitors. The efforts yielded compound 6h with promising spleen tyrosine kinase inhibition in both enzymatic and B-lymphoma cell proliferation assays. Additionally, compound 6h dose dependently inhibited the activation of spleen tyrosine kinase signal in human B-cell lymphoma cells. Compound 6h might serve as a lead for further development of new spleen tyrosine kinase inhibitors.
College of Pharmacy, Jilin University, Changchun, China.
Jiayi
J
Shen
College of Pharmacy, Jilin University, Changchun, China.
Xiaokai
X
Li
State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Zhang
Z
Zhang
State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Jingfeng
J
Luo
State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Huoyou
H
Long
State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Zhengchao
Z
Tu
College of Pharmacy, Jilin University, Changchun, China. zhouxp@jlu.edu.cn.
Xiaoping
X
Zhou
State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. ding_ke@gibh.ac.cn.|School of Pharmacy, Jinan University, Guangzhou, China. ding_ke@gibh.ac.cn.
Ke
K
Ding
School of Pharmacy, Jinan University, Guangzhou, China. lu_xiaoyun@gibh.ac.cn.
Xiaoyun
X
Lu
D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D017434:Protein Structure, Tertiary; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000201:enzymology*; D013329:Structure-Activity Relationship; D000072377:Syk Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism
C000620493:1-(3-(2H-1,2,3-triazol-2-yl)phenyl)-N-6-(2-aminocyclohexyl)-1H-pyrazolo(3,4-b)pyrazine-3,6-diamine; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D011720:Pyrazoles; D011725:Pyridines; C118531:pyrazolopyridine; D000072377:Syk Kinase
design and synthesis; inhibitors; pyrazolopyrazine-3-amine; pyrazolopyrimidine-3-amine; spleen tyrosine kinase