Portal de Periódicos da CAPES

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

2009; Elsevier BV; Volume: 19; Issue: 5 Linguagem: Inglês

10.1016/j.bmcl.2009.01.041

1464-3405

Haishan Wang, Niefang Yu, Hongyan Song, Dizhong Chen, Yong Zou, Weiping Deng, Pek Ling Lye, Joyce Wei Wei Chang, Melvin Ng, Stéphanie Blanchard, Eric T. Sun, Kanda Sangthongpitag, Xukun Wang, Kee Chuan Goh, Xiaofeng Wu, Hwee Hoon Khng, Lijuan Fang, Siok Kun Goh, Wai Chung Ong, Zahid Bonday, Walter Stünkel, Anders Poulsen, Michael Entzeroth,

Click Chemistry and Applications

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.