Author/Authors :
Han-Cheng Zhang، نويسنده , , Hong Ye، نويسنده , , Bruce R. Conway، نويسنده , , Claudia K. Derian، نويسنده , , Michael F. Addo، نويسنده , , Gee-Hong Kuo، نويسنده , , Leonard R. Hecker، نويسنده , , Diane R. Croll، نويسنده , , Jian Li، نويسنده , , Lori Westover، نويسنده , , Jun Z. Xu، نويسنده , , Richard Look، نويسنده , , Keith T. Demarest، نويسنده , , Patricia Andrade-Gordon، نويسنده , , Bruce P. Damiano، نويسنده , , Bruce E. Maryanoff، نويسنده ,
Abstract :
A novel series of acyclic 3-(7-azaindolyl)-4-(aryl/heteroaryl)maleimides was synthesized and evaluated for activity against GSK-3β and selectivity versus PKC-βII, as well as a broad panel of protein kinases. Compounds 14 and 17c potently inhibited GSK-3β (IC50=7 and 26 nM, respectively) and exhibited excellent selectivity over PKC-βII (325 and >385-fold, respectively). Compound 17c was also highly selective against 68 other protein kinases. In a cell-based functional assay, both 14 and 17c effectively increased glycogen synthase activity by inhibiting GSK-3β.
Keywords :
Azaindolylmaleimides.* Corresponding author. Tel.: +1-215-628-5988 , e-mail: hzhang@prdus.jnj.com , fax: +1-215-628-4985 , GSK-3 inhibitors , Kinases
