2. Academic Validation
  3. 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

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

  • Bioorg Med Chem. 2017 Jan 15;25(2):765-772. doi: 10.1016/j.bmc.2016.11.054.
Yang Ge 1,  Haijun Yang 1,  Changyuan Wang 1,  Qiang Meng 1,  Lei Li 1,  Huijun Sun 1,  Yuhong Zhen 1,  Kexin Liu 1,  Yanxia Li 2,  Xiaodong Ma 3
Affiliations

Affiliations

  • 1 College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
  • 2 Department of Respiratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.
  • 3 College of Pharmacy, Dalian Medical University, Dalian 116044, PR China. Electronic address: xiaodong.ma@139.com.
PMID: 27956037 DOI: 10.1016/j.bmc.2016.11.054
Abstract

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 0.82nmol/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 3.17μM and 6.69μM. 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.

Keywords

BTK; DPPY; Inhibitor; Leukemia; Phosphoryl.

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