Bioorganic & Medicinal Chemistry 2011-09-15

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

Susumu Watanuki, Keisuke Matsuura, Yuichi Tomura, Minoru Okada, Toshio Okazaki, Mitsuaki Ohta, Shin-Ichi Tsukamoto

文献索引：Bioorg. Med. Chem. 19(18) , 5628-5638, (2011)

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摘要

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.Copyright © 2011 Elsevier Ltd. All rights reserved.