title: Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors.
abstract: A series of novel 3,5-diamino-1,2,4-triazole benzyl ureas was identified as having potent anaplastic lymphoma kinase (ALK) inhibition exemplified by 15a, 20a, and 23a, which exhibited antiproliferative IC(50) values of 70, 40, and 20 nM in Tel-ALK transformed Ba/F3 cells, respectively. Moreover, 15a and 23a potently inhibited the growth and survival of NPM-ALK positive anaplastic large cell lymphoma cell (SU-DHL-1) and neuroblastoma cell lines (KELLY, SH-SY5Y) containing the F1174L ALK mutation. These compounds provide novel leads for the development of small-molecule ALK inhibitors for cancer therapy.
authors.forename: Xianming
authors.initials: X
authors.lastname: Deng
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Jianming
authors.initials: J
authors.lastname: Zhang
authors.forename: Taebo
authors.initials: T
authors.lastname: Sim
authors.forename: Nam Doo
authors.initials: ND
authors.lastname: Kim
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sasaki
authors.forename: William
authors.initials: W
authors.lastname: Luther
authors.forename: Rani E
authors.initials: RE
authors.lastname: George
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Nathanael S
authors.initials: NS
authors.lastname: Gray