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. Issue 2 (15th January 2017)

• Record Type: Journal Article
• Authors: Ge, Yang; Yang, Haijun; Wang, Changyuan; Meng, Qiang; Li, Lei; Sun, Huijun; Zhen, Yuhong; Liu, Kexin; Li, Yanxia; Ma, Xiaodong
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 2(2017)
• Page Start: 765
• Page End: 772
• Publication Date: 2017-01-15
• Subjects: Leukemia -- BTK -- DPPY -- Phosphoryl -- Inhibitor; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.11.054
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A family of phosphoryl-substituted diphenylpyrimidine derivatives (Pho-DPPYs) were synthesized and biologically evaluated as potent BTK inhibitors in this study. Compound7b 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 that7b promoted cell apoptosis to a substantial degree. In a word, compound7b is a promising BTK inhibitor for the treatment of B-cell lymphoblastic leukemia.