AN EFFICIENT SYNTHESIS OF (3S,5S)-5-[3,3-DIMETHYL-1-(o-TOLYL)-6-OXO-2H-PYRIDIN-4-YL]PIPERIDINE-3-CARBOXAMIDE AS POTENT RENIN INHIBITOR

We report synthesis and biological evaluation of (3S,5S)-5-[3,3-dimethyl-1-(o-tolyl)-6-oxo-2H-pyridin-4-yl]piperidine-3-carboxamide as renin inhibitor. This effective synthetic route involves a zinc mediated Barbier reaction and an intramolecular Horner-Wadsworth-Emmons reaction of sterically hindered ketone as key reactions. The prepared compound 4 exhibited both potent renin inhibitory activity and significant in vivo efficacy in furosemide pretreated cynomolgus monkeys.