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

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 IC 50 values in the nanomolar range and inhibit tumor cell proliferation...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010, Vol.20 (1), p.294-298
Main Authors: Angibaud, Patrick, Emelen, Kristof Van, Decrane, Laurence, Brandt, Sven van, Holte, Peter ten, Pilatte, Isabelle, Roux, Bruno, Poncelet, Virginie, Speybrouck, David, Queguiner, Laurence, Gaurrand, Sandrine, Mariën, Ann, Floren, Wim, Janssen, Lut, Verdonck, Marc, Dun, Jacky van, Gompel, Jacky van, Gilissen, Ron, Mackie, Claire, Jardin, Marc Du, Peeters, Jozef, Noppe, Marc, Hijfte, Luc Van, Freyne, Eddy, Page, Martin, Janicot, Michel, Arts, Janine
Format: Article
Language:English
Subjects:
Animals
Anti-cancer agents
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation
Drug Design
General aspects
HDAC inhibitors
Histone deacetylase
Histone Deacetylase Inhibitors - chemical synthesis
Histone Deacetylase Inhibitors - chemistry
Histone Deacetylase Inhibitors - pharmacology
Histone Deacetylases - chemistry
Histone Deacetylases - metabolism
Hydroxamic Acids - chemical synthesis
Hydroxamic Acids - chemistry
Hydroxamic Acids - pharmacology
Medical sciences
Mice
Mice, Nude
Petasis
Pharmacology. Drug treatments
Pyrimidylhydroxamic acid
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
Xenograft Model Antitumor Assays
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Summary: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 IC 50 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.10.118