Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors

Toshio Nakamura; Hiroyuki Kakinuma; Hiroki Umemiya; Hideaki Amada; Noriyuki Miyata; Kazuo Taniguchi; Kagumi Bando; Masakazu Sato

doi:10.1016/j.bmcl.2003.11.005

Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors

Bioorg Med Chem Lett. 2004 Jan 19;14(2):333-6. doi: 10.1016/j.bmcl.2003.11.005.

Authors

Toshio Nakamura¹, Hiroyuki Kakinuma, Hiroki Umemiya, Hideaki Amada, Noriyuki Miyata, Kazuo Taniguchi, Kagumi Bando, Masakazu Sato

Affiliation

¹ Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 330-8530, Yoshino-cho, Ohmiya, Saitama, Japan. toshio.nakamura@po.rd.taisho.co.jp

PMID: 14698153
DOI: 10.1016/j.bmcl.2003.11.005

Abstract

In a previous paper, we reported that an imidazole derivative 1 exhibited a potent inhibitory activity of 20-HETE synthase (1; IC(50) value of 5.7 nM), but this compound also exhibited little selectivity for cytochrome P450s (CYPs). We examined some derivatives of imidazole 1 which had an amino group on the side chain, and found that a dimethylaminohexyloxy derivative (3g; IC(50) value of 8.8 nM) showed potent and selective inhibitory activity.

MeSH terms

Cytochrome P-450 CYP2D6 / metabolism
Cytochrome P-450 CYP2D6 Inhibitors
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Humans
Hydroxyeicosatetraenoic Acids / antagonists & inhibitors*
Hydroxyeicosatetraenoic Acids / metabolism
Imidazoles / chemistry*
Imidazoles / pharmacology
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Microsomes / drug effects
Microsomes / enzymology

Substances

Cytochrome P-450 CYP2D6 Inhibitors
Enzyme Inhibitors
Hydroxyeicosatetraenoic Acids
Imidazoles
Isoenzymes
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Cytochrome P-450 CYP2D6