Synthesis and biochemical evaluation of a range of (4-substituted phenyl) sulfonate derivatives of 4-hydroxybenzyl imidazole-based compounds as potent inhibitors of 17α-hydroxylase/17,20-lyase (P45017α) derived from rat testicular microsomes

被引：6

作者：

Owen, Caroline P. ^{[1
]}

Shahid, Imran

Lee, Wai-Yee

Ahmed, Sabbir ^{[1
]}

机构：

[1] Univ W Scotland, Fac Sci & Technol, Sch Sci, Paisley PA1 2BE, Renfrew, Scotland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 17期

关键词：

Synthesis; Inhibition; Enzyme; 17; alpha-Hydroxylase; 17,20-Lyase; PROSTATE-CANCER; ENZYME; RATIONALIZATION; P-450(17-ALPHA); CYP17;

D O I：

10.1016/j.bmcl.2010.02.100

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a range of (4-substituted phenyl)sulfonate derivatives of 4-hydroxybenzyl imidazole against the two components of 17 alpha-hydroxylase/17,20-lyase (P450(17 alpha)), namely, 17 alpha-hydroxylase (17 alpha-OHase) and 17,20-lyase (lyase). The results show the compounds to be highly potent inhibitors with limited selectivity towards the lyase component [e.g., toluene-4-sulfonic acid 4-imidazol-1-ylmethyl-phenyl ester (4) possessed an IC50 value of 40 nM against 17 alpha-OHase and 30 nM against lyase]. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：5345 / 5348

页数：4

共 8 条

[1] Synthesis and biochemical evaluation of a range of sulfonated derivatives of 4-hydroxybenzyl imidazole as highly potent inhibitors of rat testicular 17α-hydroxylase/17,20-lyase (P-45017α)
Ahmed, Sabbir
Shahid, Imran
Dhanani, Sachin
Owen, Caroline P.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (16) : 4698 - 4701
[2] Synthesis, biochemical evaluation of a range of potent 4-substituted phenyl alkyl imidazole-based inhibitors of the enzyme complex 17α-hydroxylase/17,20-Lyase (P45017α)
Shahid, Imran
Patel, Chirag H.
Dhanani, Sachin
Owen, Caroline P.
Ahmed, Sabbir
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2008, 110 (1-2) : 18 - 29
[3] Synthesis and Biochemical Evaluation of a Range of 2-, 3-and 4-Substituted Derivatives of Benzyl Imidazole-Based Compounds as Probes of the Active Site of 17α-hydroxylase/17,20-Lyase (P45017α)
Ahmed, Sabbir
Shahid, Imran
Bhatti, Kishore K.
Lee, Wai-Yee
Owen, Caroline P.
LETTERS IN DRUG DESIGN & DISCOVERY, 2009, 6 (07) : 524 - 530
[4] Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a range of 4-substituted phenyl alkyl imidazole-based inhibitors of the enzyme complex 17α-hydroxylase/17,20-lyase (P45017α)
Patel, Chirag H.
Dhanani, Sachin
Owen, Caroline P.
Ahmed, Sabbir
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (18) : 4752 - 4756
[5] Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a range of phenyl alkyl imidazole-based compounds as potent inhibitors of the enzyme complex 17α-hydroxlase/17,20-lyase (P45017α)
Owen, Caroline P.
Shahid, Imran
Olusanjoa, Moniola S.
Patel, Chirag H.
Dhanani, Sachin
Ahmed, Sabbir
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2008, 111 (1-2) : 117 - 127
[6] Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a series of 4-substituted phenyl alkyl triazole-based compounds as potential inhibitors of 17α-hydroxylase/17,20-lyase (P45017α)
Owen, Caroline P.
Dhanani, Sachin
Patel, Chirag H.
Ahmed, Sabbir
LETTERS IN DRUG DESIGN & DISCOVERY, 2007, 4 (07) : 479 - 483
[7] Synthesis and Biochemical Evaluation of a Range of 4-(n-alkanesul-fonate)benzyl Imidazole-Based Compounds as Inhibitors of Rat Testicular 17α-hydroxylase/17,20-lyase (P45017α) in the Treatment of Hormone-Dependent Prostate Cancer
Shah, Pallav S.
Shahid, Imran
Lee, Wai-Yee
Owen, Caroline P.
Ahmed, Sabbir
LETTERS IN DRUG DESIGN & DISCOVERY, 2014, 11 (08) : 1000 - 1009
[8] Synthesis, Biochemical Evaluation and Rationalisation of the Inhibitory Activity of a Range of Derivatives of 2-imidazol-1-yl-1-phenyl-ethanone as Potential Novel Inhibitors of 17α-hydroxylase/17,20-lyase (P-45017α)
Shah, Kruti
Jandu, Baljeet
Abdullah, Ammara
Ahmed, Sabbir
LETTERS IN DRUG DESIGN & DISCOVERY, 2011, 8 (06) : 516 - 522

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