RESUMEN
This Letter describes the continued SAR exploration of small molecule Legumain inhibitors with the aim of developing a potent and selective in vitro tool compound. Work continued in this Letter explores the use of alternative P2-P3 linker units and the P3 group SAR which led to the identification of 10t, a potent, selective and cellularly active Legumain inhibitor. We also demonstrate that 10t has activity in both cancer cell viability and colony formation assays.
Asunto(s)
Cisteína Endopeptidasas , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacocinética , Supervivencia Celular/efectos de los fármacos , Cisteína Endopeptidasas/química , Inhibidores Enzimáticos/farmacología , Concentración 50 Inhibidora , Estructura MolecularRESUMEN
The tandem ene/intramolecular Sakurai cyclisation (IMSC) reaction has been successfully applied to the synthesis of a range of C-glycosides, with key intermediates offering opportunities for functionalisation of the glycon moiety. To demonstrate the versatility of the approach to access the 2-deoxy-C-glycoside series, we synthesised diastereomerically pure C-glucoside and galactoside derivatives incorporating functionalised aromatic, heteroaromatic and bicyclic aromatic moieties, in addition to the C-homologue of (±)-ß-2-deoxy-glucose 6-phosphate.