N-Hydroxy-1,2-disubstituted-1H-benzimidazol-5-yl acrylamides as novel histone deacetylase inhibitors: design, synthesis, SAR studies, and in vivo antitumor activity.

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Wang H, Yu N, Song H, Chen D, Zou Y, Deng W, Lye PL, Chang J, Ng M, Sun ET, Sangthongpitag K, Wang X, Wu X, Khng HH, Fang L, Goh SK, Ong WC, Bonday Z, Stunkel W, Poulsen A, Entzeroth M

N-Hydroxy-1,2-disubstituted-1H-benzimidazol-5-yl acrylamides as novel histone deacetylase inhibitors: design, synthesis, SAR studies, and in vivo antitumor activity.

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1403-8. doi: 10.1016/j.bmcl.2009.01.041. Epub 2009 Jan 19.

PubMed ID

19181524 [ View in PubMed

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Abstract

A series of N-hydroxy-1,2-disubstituted-1H-benzimidazol-5-yl acrylamides were designed and synthesized as novel HDAC inhibitors. General SAR has been established for the substituents at positions 1 and 2, as well as the importance of the ethylene group and its attachment to position 5. Optimized compounds are much more potent than SAHA in both enzymatic and cellular assays. A representative compound, 23 (SB639), has demonstrated antitumor activity in a colon cancer xenograft model.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Vorinostat	Histone deacetylase 1	IC 50 (nM)	120	N/A	N/A	Details