Synthesis and CYP24A1 inhibitory activity of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides

被引：16

作者：

Aboraia, Ahmed S. ^{[1
]}

Yee, Sook Wah ^{[1
]}

Gomaa, Mohamed Sayed ^{[1
]}

Shah, Nikhil ^{[1
]}

Robotham, Anna C. ^{[2
]}

Makowski, Bart ^{[2
]}

Prosser, David ^{[2
]}

Brancale, Andrea ^{[1
]}

Jones, Glenville ^{[2
]}

Simons, Claire ^{[1
]}

机构：

[1] Cardiff Univ, Welsh Sch Pharm, Cardiff CF10 3NB, S Glam, Wales

[2] Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 14期

关键词：

N-(2-(1H-Imidazol-1-yl)-2-phenylethyl)arylamides; Benzofuran-2-carboxamides; CYP24A1; Enzyme inhibition; Molecular modelling; PROSTATE-CANCER CELLS; HORMONE; 1-ALPHA; 25-DIHYDROXYVITAMIN D-3; VITAMIN-D ANALOGS; DERIVATIVES; VDR;

D O I：

10.1016/j.bmc.2010.06.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides were prepared, using an efficient three-to five-step synthesis, and evaluated for their inhibitory activity against human cytochrome P450C24A1 (CYP24A1) hydroxylase. Inhibition ranged from IC50 0.3-72 mu M compared with the standard ketoconazole IC50 0.52 mu M, with the styryl derivative (11c) displaying enhanced activity (IC50 = 0.3 mu M) compared with the standard, providing a useful preliminary lead for drug development. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4939 / 4946

页数：8

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