title: 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.
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.
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ge
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Meng
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhen
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Respiratory, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, PR China. Electronic address: xiaodong.ma@139.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Ma
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human
keywords: BTK; DPPY; Inhibitor; Leukemia; Phosphoryl