Aminopyridyl/pyrazinyl spiro[indoline-3,4′-piperidine]-2-ones as highly selective and efficacious c-met/ALK inhibitors

Article abstract of DOI:10.1021/ml400203d

A series of novel aminopyridyl/pyrazinyl-substituted spiro[indoline-3, 4′-piperidine]-2-ones were designed, synthesized, and tested in various in vitro/in vivo pharmacological and antitumor assays. 6-[6-Amino-5-[(1R)-1-(2,6- dichloro-3-fluorophenyl)ethoxy]-3-pyridyl]-1′-methylspiro[indoline-3, 4′-piperidine]-2-one (compound 5b or SMU-B) was identified as a potent, highly selective, well-tolerated, and orally efficacious c-Met/ALK dual inhibitor, which showed pharmacodynamics effect by inhibiting c-Met phosphorylation in vivo and significant tumor growth inhibitions (>50%) in GTL-16 human gastric carcinoma xenograft models.