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

共 7 条

[1] Design and synthesis of sulfonamide-substituted diphenylpyrimidines (SFA-DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B-cell lymphoblastic leukemia
Liu, He
Qu, Menghua
Xu, Lina
Han, Xu
Wang, Chanyuan
Shu, Xiaohong
Yao, Jihong
Liu, Kexin
Peng, Jinyong
Li, Yanxia
Ma, Xiaodong
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 135 : 60 - 69
[2] Structural optimization of diphenylpyrimidine derivatives (DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B leukemia cell lines
Zhao, Dan
Huang, Shanshan
Qu, Menghua
Wang, Changyuan
Liu, Zhihao
Li, Zhen
Peng, Jinyong
Liu, Kexin
Li, Yanxia
Ma, Xiaodong
Shu, Xiaohong
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 126 : 444 - 455
[3] Design, synthesis and biological evaluation of novel 3-substituted pyrazolopyrimidine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors
Zheng, Nan
Pan, Jing
Hao, Qun
Li, Yingxia
Zhou, Weicheng
BIOORGANIC & MEDICINAL CHEMISTRY, 2018, 26 (08) : 2165 - 2172
[4] Design, synthesis and evaluation of novel 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as potent, selective and reversible Bruton's tyrosine kinase (BTK) inhibitors for the treatment of rheumatoid arthritis
Zhang, Chufeng
Pei, Heying
He, Jun
Zhu, Jiali
Li, Weimin
Niu, Ting
Xiang, Mingli
Chen, Lijuan
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 169 : 121 - 143
[5] Design, Synthesis, and In Vitro and In Vivo Evaluation of Cereblon Binding Bruton's Tyrosine Kinase (BTK) Degrader CD79b Targeted Antibody-Drug Conjugates
Zhang, Alan
Seiss, Katherine
Laborde, Laurent
Palacio-Ramirez, Sebastian
Guthy, Daniel
Lanter, Mylene
Lorber, Julien
Vulpetti, Anna
Arista, Luca
Zoller, Thomas
Radimerski, Thomas
Thoma, Claudio
Hebach, Christina
Tschantz, William R.
Karpov, Alexei
Hollingworth, Gregory J.
D'Alessio, Joseph A.
Ferretti, Stephane
Burger, Matthew T.
BIOCONJUGATE CHEMISTRY, 2024, 35 (02) : 140 - 146
[6] Synthesis and biological evaluation of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c] pyridin-4-amines as potent Bruton's tyrosine kinase (BTK) inhibitors
Xin, Minhang
Zhao, Xinge
Huang, Wei
Jin, Qiu
Wu, Gang
Wang, Yazhou
Tang, Feng
Xiang, Hua
BIOORGANIC & MEDICINAL CHEMISTRY, 2015, 23 (19) : 6250 - 6257
[7] 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
Zheng, Nan
Hao, Qun
Lin, Kuaile
Pan, Jing
Li, Yingxia
Zhou, Weicheng
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2019, 29 (02) : 225 - 229

← 1 →