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

Autor:	Hong Yan Song, Melvin Ng, Zou Yong, Eric T. Sun, Michael Entzeroth, Anders Poulsen, Dizhong Chen, Kee Chuan Goh, Joyce Wei Wei Chang, Kanda Sangthongpitag, Walter Stünkel, Niefang Yu, Zahid Bonday, Haishan Wang, Weiping Deng, Lye Pek Ling, Stéphanie Blanchard, Hwee Hoon Khng, Wai Chung Ong, Lijuan Fang, Xiaofeng Wu, Xukun Wang, Siok Kun Goh
Rok vydání:	2009
Předmět:	Benzimidazole Ethylene Stereochemistry Clinical Biochemistry Mice Nude Pharmaceutical Science Antineoplastic Agents Crystallography X-Ray Biochemistry Histone Deacetylases Mice Structure-Activity Relationship chemistry.chemical_compound In vivo Cell Line Tumor Drug Discovery Animals Humans Structure–activity relationship Molecular Biology chemistry.chemical_classification Acrylamides Hydroxamic acid Organic Chemistry HCT116 Cells Xenograft Model Antitumor Assays Histone Deacetylase Inhibitors Enzyme chemistry Cell culture Molecular Medicine Benzimidazoles Female Histone deacetylase Drug Screening Assays Antitumor
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 19:1403-1408
ISSN:	0960-894X
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a3e376a61c5bc6b4d1fe18f5fae12e01 https://doi.org/10.1016/j.bmcl.2009.01.041 Zobrazit plný text záznamu Full Text from ScienceDirect