Synthesis and evaluation of lysine derived sulfamides as histone deacetylase inhibitors

被引：21

作者：

Manku, Sukhdev ^{[1
]}

Allan, Martin ^{[1
]}

Nguyen, Natalie ^{[1
]}

Ajamian, Alain ^{[1
]}

Rodrigue, Jacques ^{[1
]}

Therrien, Eric ^{[1
]}

Wang, James

Guo, Tim

Rahil, Jubrail ^{[2
]}

Petschner, Andrea J. ^{[2
]}

Nicolescu, Alina ^{[2
]}

Lefebvre, Sylvain

Li, Zuomei

Fournel, Marielle

Besterman, Jeffrey M.

Deziel, Robert ^{[1
]}

Wahhab, Amal ^{[1
]}

机构：

[1] MethylGene Inc, Dept Med Chem, Montreal, PQ H4S 2A1, Canada

[2] Lead Discovery, Montreal, PQ H4S 2A1, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 07期

关键词：

Sulfamides; HDAC inhibitors; HDAC1; HDAC6; POTENT; CANCER; SERIES;

D O I：

10.1016/j.bmcl.2009.02.075

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have recently reported on a novel class of histone deacetylase (HDAC) inhibitors bearing a sulfamide group as the zinc-binding unit. Herein, we report on the synthesis of sulfamide based inhibitors designed around a lysine scaffold and their structure-activity relationships against HDAC1 and HDAC6 isotypes as well as 293T cells. Our efforts led us to an improvement of the originally disclosed lysine-based sulfamide, 2a to compound 12h which has equal potency in enzyme and cell-based assays as well as enhanced metabolic stability and PK profile. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1866 / 1870

页数：5

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