Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers

Morpholin-2-one-5-carboxamide derivatives were prepared by using the one-pot Ugi multicomponent reaction and evaluated for blocking effects on T- and N-type Ca2+ channels. Among them, compound 5i produced the highest potency (IC50 = 0.45 ± 0.02 μM), while compounds 5d, 5f, 5k, 5n, 5o, and 6m produced relatively high potency as well as selectivity on T-type Ca2+ channels. These novel scaffolds showed potent and selective T-type Ca2+ channel blocking activities.

Graphical abstractMorpholin-2-one-5-carboxamide derivatives were prepared by using a one-pot Ugi multicomponent reaction and showed potent and selective T-type calcium channel blocking activities.Figure optionsDownload full-size imageDownload as PowerPoint slide