Discovery of a N '-hydroxyphenylformamidine derivative HET0016 as a potentand selective 20-HETE synthase inhibitor

Citation
M. Sato et al., Discovery of a N '-hydroxyphenylformamidine derivative HET0016 as a potentand selective 20-HETE synthase inhibitor, BIOORG MED, 11(23), 2001, pp. 2993-2995
Citations number
12
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960-894X → ACNP
Volume
11
Issue
23
Year of publication
2001
Pages
2993 - 2995
Database
ISI
SICI code
0960-894X(200112)11:23<2993:DOAN'D>2.0.ZU;2-A
Abstract
N-(4-Butyl-2-methylphenyl)-N'-hydroxyformamidine (HET0016) was evaluated as the first potent and selective inhibitor of 20-hydroxy-5,8,11,14-eicosatet raenoic acid (20-HETE) synthase. The IC50 value of HET0016 for the producti on of 20-HETE from arachidonic acid (AA) by human renal microsomes was 8.9 +/- 2.7 nM, with over 200 times the selectivity of xenobiotic-metabolizing cytochrome P450 enzymes. An examination of the structure-activity relations hip revealed that the unsubstituted hydroxyformamidine moiety and the subst ituent at the para-position of the N-hydroxyformamidine moiety are necessar y for the potent activity of HET0016. (C) 2001 Elsevier Science Ltd. All ri ghts reserved.