- Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.
Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.
Journal of medicinal chemistry (2016-05-25)
Zhen Wang, Huan Bian, Sergio G Bartual, Wenting Du, Jinfeng Luo, Hu Zhao, Shasha Zhang, Cheng Mo, Yang Zhou, Yong Xu, Zhengchao Tu, Xiaomei Ren, Xiaoyun Lu, Rolf A Brekken, Libo Yao, Alex N Bullock, Jin Su, Ke Ding
PMID27219676
ZUSAMMENFASSUNG
The structure-based design of 1, 2, 3, 4-tetrahydroisoquinoline derivatives as selective DDR1 inhibitors is reported. One of the representative compounds, 6j, binds to DDR1 with a Kd value of 4.7 nM and suppresses its kinase activity with an IC50 value of 9.4 nM, but it is significantly less potent for a panel of 400 nonmutated kinases. 6j also demonstrated reasonable pharmacokinetic properties and a promising oral therapeutic effect in a bleomycin-induced mouse pulmonary fibrosis model.
MATERIALIEN