gsk-1363089 and 1-4-dihydroquinoline

A series of 4-(2-fluorophenoxy)quinoline derivatives bearing the 4-oxo-1,4-dihydroquinoline-3-carboxamide moiety were designed, synthesized, and evaluated for their in vitro antitumor activity against the H460, HT-29, MKN-45, U87MG, and SMMC-7721 cancer cell lines. Most of the tested compounds showed potent activity and high selectivity toward the HT-29 and MKN-45 cell lines. Furthermore, compounds 21b, 21c, and 21i were further examined for their c-Met kinase activity and exhibited strong efficacy with IC50 values in the single-digit nanomolar range, which was comparable with the positive control foretinib. The most promising compound 21c showed excellent cytostatic activity with IC50 values from 0.01 to 0.53 µM against all tested cell lines, thus being 1.7-2.2 times more active than foretinib.

Topics: Anilides; Antineoplastic Agents; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; HT29 Cells; Humans; Inhibitory Concentration 50; Molecular Structure; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Quinolines; Structure-Activity Relationship