Design, syntheses, and SAR of 2,8-diazaspiro[4.5]decanones as T-type calcium channel antagonists

It was hypothesized that an appropriately substituted 2,8-diazaspiro4.5]decan-1-one could effectively approximate a 5-feature T-type pharmacophore model published in the literature. Compounds were designed and synthesized to test our hypothesis and were found to be potent T-type calcium channel inhibitors with modest selectivity over L-type calcium channels. The synthesis and SAR of the series is described.