Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors

被引：77

作者：

Benelkebir, Hanae ^{[1
]}

Hodgkinson, Christopher ^{[1
]}

Duriez, Patrick J. ^{[2
]}

Hayden, Annette L. ^{[3
]}

Bulleid, Rosemary A. ^{[3
]}

Crabb, Simon J. ^{[3
]}

Packham, Graham ^{[3
]}

Ganesan, A. ^{[1
]}

机构：

[1] Univ Southampton, Sch Chem, Southampton SO17 1BJ, Hants, England

[2] Univ Southampton, Southampton Gen Hosp, Canc Res UK Prot Core Facil, Fac Med, Southampton SO16 6YD, Hants, England

[3] Univ Southampton, Southampton Gen Hosp, Canc Res UK Ctr, Fac Med, Southampton SO16 6YD, Hants, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 12期

关键词：

Epigenetics; Prostate cancer; Lysine demethylase; Enzyme inhibitors; HISTONE DEMETHYLASE; CYCLOPROPANATION; OXIDASE; TRANS-2-PHENYLCYCLOPROPYLAMINE; EPIGENETICS; TARGET; DNA;

D O I：

10.1016/j.bmc.2011.02.017

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：

Asymmetric cyclopropanation of styrenes by tert-butyl diazoacetate followed by ester hydrolysis and Curtius rearrangement gave a series of tranylcypromine analogues as single enantiomers. The o - m-and p-bromo analogues were all more active than tranylcypromine in a LSD1 enzyme assay. The m-and p-bromo analogues were micromolar growth inhibitors of the LNCaP prostate cancer cell line as were the corresponding biphenyl analogues prepared from the bromide by Suzuki crosscoupling. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：3709 / 3716

页数：8

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