Synthesis and pharmacological evaluation of 2-(1-alkylpiperidin-4-yl)-n-[(1r)-1-(4-fluorophenyl)-2-methylpropyl]acetamide Derivatives as Novel Antihypertensive Agents.

摘要: We synthesized and evaluated the inhibitory activity of a series 2-(1-alkylpiperidin-4-yl)-N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]acetamide derivatives against T-type Ca2+ channels. Structure–activity relationship studies revealed that position amide structure was important for potent toward In addition, introduction an appropriate substituent on pendant benzene ring played crucial role selectivity towards channels over L-type bradycardic these derivatives. Oral administration N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]-2-(1-{2-[2-(2-methoxyethoxy)phenyl]ethyl}piperidin-4-yl)acetamide (4f), which had superior channels, lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, is often caused by traditional channel blockers.