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

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• 作者：Yang Ge^a ; ¹ ; Haijun Yang^a ; ¹ ; Changyuan Wang^a ; Qiang Meng^a ; Lei Li^a ; Huijun Sun^a ; Yuhong Zhen^a ; Kexin Liu^a ; Yanxia Li^b ; Xiaodong Ma^a ; ^{xiaodong.ma@139.com}
• 关键词：Leukemia ; BTK ; DPPY ; Phosphoryl ; Inhibitor
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：25
• 期：2
• 页码：765-772
• 全文大小：2348 K
• 卷排序：25

文摘

A family of phosphoryl-substituted diphenylpyrimidine derivatives (Pho-DPPYs) 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 μM and 6.69 μM. 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.