Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors.
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.
Nakamura
Toshio
T
Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 330-8530, Yoshino-cho, Ohmiya, Saitama, Japan. toshio.nakamura@po.rd.taisho.co.jp
Kakinuma
Hiroyuki
H
Umemiya
Hiroki
H
Amada
Hideaki
H
Miyata
Noriyuki
N
Taniguchi
Kazuo
K
Bando
Kagumi
K
Sato
Masakazu
M
D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology
D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D007093:Imidazoles; D007527:Isoenzymes; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D019389:Cytochrome P-450 CYP2D6