Synthesis and pharmacological evaluation of 1-alkyl-N-[2-ethyl-2-(4-fluorophenyl)butyl]piperidine-4-carboxamide derivatives as novel antihypertensive agents.

Article Details

Citation

Copy to clipboard

Watanuki S, Matsuura K, Tomura Y, Okada M, Okazaki T, Ohta M, Tsukamoto S

Synthesis and pharmacological evaluation of 1-alkyl-N-[2-ethyl-2-(4-fluorophenyl)butyl]piperidine-4-carboxamide derivatives as novel antihypertensive agents.

Bioorg Med Chem. 2011 Sep 15;19(18):5628-38. doi: 10.1016/j.bmc.2011.07.030. Epub 2011 Jul 29.

PubMed ID

21875808 [ View in PubMed

]

Abstract

We synthesized and evaluated inhibitory activity against T-type Ca(2+) channels for a series of 1-alkyl-N-[2-ethyl-2-(4-fluorophenyl)butyl]piperidine-4-carboxamide derivatives. Structure-activity relationship studies have revealed that dialkyl substituents at the benzylic position play an important role in increasing inhibitory activity. Oral administration of N-[2-ethyl-2-(4-fluorophenyl)butyl]-1-(2-phenylethyl)piperidine-4-carboxamide (20d) lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, which is often caused by traditional L-type Ca(2+) channel blockers.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Mibefradil	Voltage-dependent T-type calcium channel subunit alpha-1G	IC 50 (nM)	200	N/A	N/A	Details