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

页码：765 / 772

页数：8

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