Synthesis and biological evaluation of novel 1-substituted 3-(3-phenoxyprop-1-yn-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amines as potent Bruton's tyrosine kinase (BTK) inhibitors

被引：12
|
作者：
Zheng, Nan [1 ,2 ]
Hao, Qun [1 ]
Lin, Kuaile [1 ]
Pan, Jing [1 ,2 ]
Li, Yingxia [2 ]
Zhou, Weicheng [1 ]
机构：
[1] China State Inst Pharmaceut Ind, Shanghai Key Lab Antiinfect, State Key Lab New Drug & Pharmaceut Proc, Shanghai Inst Pharmaceut Ind, 285 Gebaini Rd, Shanghai 201203, Peoples R China
[2] Fudan Univ, Sch Pharm, 826 Zhangheng Rd, Shanghai 201203, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 02期
关键词：
BTK inhibitors; 1-Substituted pyrazolo[3,4-d]pyrimidine; Inhibitory activity; B-cell lymphoblastic leukemia; Cytotoxicity; B-CELL; DISCOVERY; IBRUTINIB;
D O I：
10.1016/j.bmcl.2018.11.051
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A new series of 1-substituted pyrazolopyrimidine derivatives were synthesized as potent BTK inhibitors and they were evaluated by enzyme-based assay and anti-proliferation against multiple B-cell lymphoma cell lines in vitro. Among these compounds, 9h exhibited the highest potency against BTK enzyme, with IC50 value of 4.2 nM. In particular, 8 and 9f performed better inhibition against the proliferation of B lymphoma cell lines DOHH2 and WSU-DLCL2 than the clinical drug ibrutinb. In addition, the test toward the normal PBMC cells showed that 8 possessed low cell cytotoxicity. All these explorations indicated that 8 could serve as a valuable anti-tumor agent for B-cell lymphoblastic leukemia treatment.
引用
收藏
页码：225 / 229
页数：5
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