Design and synthesis of phosphoryl-substituted diphenylpyrimidines (Pho-DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors: Targeted treatment of B lymphoblastic leukemia cell lines

被引：19
|
作者：
Ge, Yang [1 ]
Yang, Haijun [1 ]
Wang, Changyuan [1 ]
Meng, Qiang [1 ]
Li, Lei [1 ]
Sun, Huijun [1 ]
Zhen, Yuhong [1 ]
Liu, Kexin [1 ]
Li, Yanxia [2 ]
Ma, Xiaodong [1 ]
机构：
[1] Dalian Med Univ, Coll Pharm, Dalian 116044, Peoples R China
[2] Dalian Med Univ, Affiliated Hosp 1, Dept Resp, Dalian 116011, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 02期
基金：
中国国家自然科学基金;
关键词：
Leukemia; BTK; DPPY; Phosphoryl; Inhibitor; CHRONIC LYMPHOCYTIC-LEUKEMIA; TEC FAMILY KINASES; IRREVERSIBLE INHIBITORS; ACTIVATION; DISCOVERY; RECEPTOR; DRUG; LYMPHOMA; PRODRUGS; TRIAL;
D O I：
10.1016/j.bmc.2016.11.054
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A family of phosphoryl-substituted diphenylpyrimidine derivatives (Pho-DPPY5) were synthesized and biologically evaluated as potent BTK inhibitors in this study. Compound 7b was found to markedly inhibit BTK activity at concentrations of 0.82 nmol/L, as well as to suppress the proliferations of B-cell leukemia cell lines (Ramos and Raji) expressing high levels of BTK at concentrations of 3.17 mu M and 6.69 mu M. Moreover, flow cytometry analysis results further indicated that 7b promoted cell apoptosis to a substantial degree. In a word, compound 7b is a promising BTK inhibitor for the treatment of B-cell lymphoblastic leukemia. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码：765 / 772
页数：8
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