2. Academic Validation
  3. Aminopyridyl/Pyrazinyl Spiro[indoline-3,4'-piperidine]-2-ones As Highly Selective and Efficacious c-Met/ALK Inhibitors

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

  • ACS Med Chem Lett. 2013 Jul 12;4(8):806-10. doi: 10.1021/ml400203d.
Jingrong Li 1,  Nan Wu 2,  Yuanxin Tian 1,  Jiajie Zhang 1,  Shuguang Wu 1
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Southern Medical University , 1838 North Guangzhou Boulevard, Guangzhou 510515, China.
  • 2 Department of Neurosurgery, Southwest Hospital, Third Military Medical University , Chongqing 400038, China.
PMID: 24900750 DOI: 10.1021/ml400203d
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-[(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.

Keywords

Hepatocyte growth factor receptor (HGFR or c-Met); aminopyrazine; aminopyridine; anaplastic lymphoma kinase (ALK); cancer; inhibitor; small molecule; spiro[indoline-3,4′-piperidine]-2-one.

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