Identification of a series of substituted 2-piperazinyl-5-pyrimidylhydroxamic acids as potent histone deacetylase inhibitors

被引：17

作者：

Angibaud, Patrick ^{[1
]}

Van Emelen, Kristof

Decrane, Laurence ^{[1
]}

van Brandt, Sven

ten Holte, Peter

Pilatte, Isabelle ^{[1
]}

Roux, Bruno ^{[1
]}

Poncelet, Virginie ^{[1
]}

Speybrouck, David ^{[1
]}

Queguiner, Laurence ^{[1
]}

Gaurrand, Sandrine ^{[1
]}

Marien, Ann ^{[3
]}

Floren, Wim ^{[3
]}

Janssen, Lut ^{[3
]}

Verdonck, Marc

van Dun, Jacky ^{[3
]}

van Gompel, Jacky ^{[2
]}

Gilissen, Ron ^{[2
]}

Mackie, Claire ^{[2
]}

Du Jardin, Marc ^{[2
]}

Peeters, Jozef ^{[2
]}

Noppe, Marc ^{[2
]}

Van Hijfte, Luc ^{[1
]}

Freyne, Eddy ^{[3
]}

Page, Martin ^{[3
]}

Janicot, Michel ^{[3
]}

Arts, Janine ^{[3
]}

机构：

[1] Orthobiotech Oncol Res & Dev, Dept Med Chem, F-27106 Val De Reuil, France

[2] J&JPRD, ADME Tox Dept, B-2340 Beerse, Belgium

[3] Orthobiotech Oncol R&D, B-2340 Beerse, Belgium

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 01期

关键词：

HDAC inhibitors; Histone deacetylase; Anti-cancer agents; Petasis; Pyrimidylhydroxamic acid; CLASS-I; DISCOVERY; THERAPY; SAHA;

D O I：

10.1016/j.bmcl.2009.10.118

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Pursuing our efforts in designing 5-pyrimidylhydroxamic acid anti-cancer agents, we have identified a new series of potent histone deacetylase (HDAC) inhibitors. These compounds exhibit enzymatic HDAC inhibiting properties with IC50 values in the nanomolar range and inhibit tumor cell proliferation at similar levels. Good solubility, moderate bioavailability, and promising in vivo activity in xenograft model made this series of compounds interesting starting points to design new potent HDAC inhibitors. (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：294 / 298

页数：5

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