title: Discovery of Novel Bruton's Tyrosine Kinase (BTK) Inhibitors Bearing aN,9-Diphenyl-9H-purin-2-amine Scaffold.
abstract: Based on the pyrimidine skeleton of EGFRT790Minhibitors, a series ofN,9-diphenyl-9H-purin-2-amine derivatives were identified as effective BTK inhibitors. Among these compounds, inhibitors10d,10i, and10j, possessing IC50values of 0.5, 0.5, and 0.4 nM, displayed anti-BTK kinase activity that was as potent as the reference compounds. In particular, compound10jsuppressed the proliferation of two typical B-cell leukemia cell lines expressing high levels of BTK with concentrations of 7.75 and 12.6 μM. The activity of the subject compound as determined by the CCK-8 method and apoptosis analysis validated that inhibitor 10jis slightly more potent than AVL-292 and ibrutinib. The results of these experimental explorations suggested that10jcould serve as a valuable molecule for control of leukemia pending further developments.
authors.affiliation: College of Pharmacy, Dalian Medical University , Dalian 116044, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ge
authors.affiliation: College of Pharmacy, Dalian Medical University , Dalian 116044, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Dalian Medical University , Dalian 116044, P. R. China.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Dalian Medical University , Dalian 116044, P. R. China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Dalian Medical University , Dalian 116044, P. R. China.
authors.forename: Zeyao
authors.initials: Z
authors.lastname: Tang
authors.affiliation: College of Pharmacy, Dalian Medical University , Dalian 116044, P. R. China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
authors.affiliation: College of Pharmacy, Dalian Medical University , Dalian 116044, P. R. China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
authors.affiliation: Respiratory Department, The First Affiliated Hospital of Dalian Medical University , Dalian 116011, P. R. China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia , Vancouver, BC V5Z 4E8, Canada.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: College of Pharmacy, Dalian Medical University , Dalian 116044, P. R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Ma
keywords: BTK inhibitor; Leukemia; activity; purin; synthesis