Aminopyridyl/Pyrazinyl Spiro[indoline-3,4′-piperidine]-2-ones As Highly Selective and Efficacious c‑Met/ALK Inhibitors

Abstract

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-[(1<i>R</i>)-1-(2,6-dichloro-3-fluorophenyl)­ethoxy]-3-pyridyl]-1′-methylspiro­[indoline-3,4′-piperidine]-2-one (compound <b>5b</b> or <b>SMU-B</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