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

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.
Susumu Watanuki 1,  Keisuke Matsuura,  Yuichi Tomura,  Minoru Okada,  Toshio Okazaki,  Mitsuaki Ohta,  Shin-Ichi Tsukamoto
Affiliations

Affiliation

  • 1 Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. susumu.watanuki@jp.astellas.com
PMID: 21875808 DOI: 10.1016/j.bmc.2011.07.030
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.

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