Discovery of Novel c-Met Inhibitors Bearing a 3-Carboxyl Piperidin-2-one Scaffold

Abstract

A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC 50 values of 8.6−81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC 50 s ranging from 0.57−16 μM.

Highly diastereoselective synthesis of piperidine-2-one-substituted pyridinium salts from pyridinium ylides, aldehydes, Michael acceptors and ammonium acetate

“…The location and type of substituents in the heterocyclic ring signi cantly affect its biological properties. A preliminary study showes that piperidin-2one derivatives are promising compounds for the development of new c-Met protein inhibitors (lung cancer), as well as for the treatment of Alzheimer's disease [17][18]. There are many examples of compounds, that include chiral piperidines, among the drugs approved by the Food and Drug Administration (FDA) [19].…”

Palladium-catalyzed decarboxylative α-allylation of thiazolidinones and azlactones with sulfonamido-substituted acyclic allylic carbonates

“…1 Among these, 5-alkylated thiazolidinones and 2-piperidones are more interesting core structural elements as they are usually encountered in numerous bioactive compounds. 2 As shown in Fig. 1, compounds I and II have been found in follicle-stimulating hormone (FSH) receptor agonists.…”