4-(Heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs as a novel class of histone deacetylase inhibitors

doi:10.1016/j.bmcl.2007.12.057

Bioorganic & Medicinal Chemistry Letters

Volume 18, Issue 4, 15 February 2008, Pages 1502-1506

https://doi.org/10.1016/j.bmcl.2007.12.057 Get rights and content

Abstract

The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs is described. Some of these compounds were shown to inhibit HDAC1 with IC₅₀ values below the micromolar range, induce hyperacetylation of histones, upregulate expression of the tumor suppressor p21^WAF1/Cip1, and inhibit proliferation of human cancer cells. In addition, certain compounds of this class were active in several human tumor xenograft models in vivo.

Graphical abstract

The synthesis and biological evaluation as histone deacetylase (HDAC) inhibitors of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides of general structure 5 is described.

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^†: Present address: Auspex Pharmaceuticals, 1261 Liberty Way, Vista, CA 92081-8356, USA.

^‡: Present address: Takeda San Diego, 10410 Science Center Drive, San Diego, CA 92121, USA.

^§: Present address: Neurochem Inc., 275 Armand-Frappier Blvd., Laval, QC, Canada H7V 4A7.

View full text

4-(Heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs as a novel class of histone deacetylase inhibitors

Abstract

Graphical abstract

Annu. Rev. Pharmacol. Toxicol.

Curr. Med. Chem. Anti-Cancer Agents

Nat. Rev. Cancer

Nat. Rev. Drug Discovery

Top. Med. Chem.

J. Cancer Res.

Cancer Chemother. Pharmacol.

Biol. Pharm. Bull.

J. Med. Chem.

Nat. Rev. Cancer

Curr. Opin. Chem. Biol.

Curr. Opin. Genet. Dev.