N-羟基-1,2-二取代-1H-苯并咪唑-5-基丙烯酰胺作为新型组蛋白去乙酰化酶抑制剂：设计、合成、构效关系研究及体内抗肿瘤活性
N-Hydroxy-1,2-disubstituted-1H-benzimidazol-5-yl acrylamides as novel histone deacetylase inhibitors: design, synthesis, SAR studies, and in vivo antitumor activity.
作者信息
Wang Haishan, Yu Niefang, Song Hongyan, Chen Dizhong, Zou Yong, Deng Weiping, Lye Pek Ling, Chang Joyce, Ng Melvin, Sun Eric T, Sangthongpitag Kanda, Wang Xukun, Wu Xiaofeng, Khng Hwee Hoon, Fang Lijuan, Goh Siok Kun, Ong Wai Chung, Bonday Zahid, Stünkel Walter, Poulsen Anders, Entzeroth Michael
机构信息
S *BIO Pte Ltd, 1 Science Park Road, #05-09 The Capricorn, Singapore Science Park II, Singapore 117528, Singapore.
出版信息
Bioorg Med Chem Lett. 2009 Mar 1;19(5):1403-8. doi: 10.1016/j.bmcl.2009.01.041. Epub 2009 Jan 19.
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.
设计并合成了一系列N-羟基-1,2-二取代-1H-苯并咪唑-5-基丙烯酰胺作为新型组蛋白去乙酰化酶（HDAC）抑制剂。已确定了1位和2位取代基的一般构效关系，以及乙烯基及其与5位连接的重要性。在酶促和细胞试验中，优化后的化合物比SAHA活性更强。代表性化合物23（SB639）在结肠癌异种移植模型中已显示出抗肿瘤活性。
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