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  • Title: N-Hydroxy-1,2-disubstituted-1H-benzimidazol-5-yl acrylamides as novel histone deacetylase inhibitors: design, synthesis, SAR studies, and in vivo antitumor activity.
    Author: 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, Stünkel W, Poulsen A, Entzeroth M.
    Journal: Bioorg Med Chem Lett; 2009 Mar 01; 19(5):1403-8. PubMed ID: 19181524.
    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.
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