Discovery of novel tetrahydroisoquinoline-containing pyrimidines as ALK inhibitors.

Basic Information

ID: ALA4715694

Journal: Bioorg Med Chem

Title: Discovery of novel tetrahydroisoquinoline-containing pyrimidines as ALK inhibitors.

Authors: Achary R,Yun JI,Park CM,Mathi GR,Lee JY,Ha JD,Chae CH,Ahn S,Park CH,Lee CO,Hwang JY,Yun CS,Jung HJ,Cho SY,Kim HR,Kim P

Abstract: Exploration of the two-position side chain of pyrimidine in LDK378 with tetrahydroisoquinolines (THIQs) led to discovery of 8 and 17 as highly potent ALK inhibitors. THIQs 8 and 17 showed encouraging in vitro and in vivo xenograft efficacies, comparable with those of LDK378. Although THIQ analogs (8a-o and 17a-i) prepared were not as active as their parent compounds, both 8 and 17 have significant inhibitory activities against various ALK mutant enzymes including G1202R, indicating that this series of compounds could be further optimized as useful ALK inhibitors overcoming the resistance issues found from crizotinib and LDK378.

CiteXplore: 26712094

DOI: 10.1016/j.bmc.2015.12.004

Patent ID: ┄