Yingjie Zhang - Design, synthesis and preliminary activity assay of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as novel Histone deacetylases (HDACs) inhibitors.

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      Publication Details (including relevant citation   information):

      Bioorg.   Med. Chem.,   2010, 18 (5), 1761-1772.


      Histone   deacetylases (HDACs) are enzymes involved in tumor genesis and   development. Herein we report a novel series of   1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as   HDACs inhibitors. The preliminary biological screening showed   that most of our compounds exhibited potent inhibitory activity   against HDACs. Within this series, five compounds,   13a (IC50=0.58±0.10 μM),   7d (IC50=1.00±0.16 μM),   8l (IC50=1.06±0.14 μM),   7i (IC50=1.17±0.19 μM) and   7a (IC50=1.29±0.15 μM) possessed   better HDACs inhibitory activity than Vorinostat   (IC50=1.48±0.20 μM). So these five compounds could be   used as novel lead compounds for further design of HDACs   inhibitors. The anti-proliferative activities of a few compounds   and the structure-activity relationships are also briefly   discussed.

      Address (URL): http://www.sciencedirect.com/science/article/pii/S096808961000091X