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.
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.
authors.affiliation: S *BIO Pte Ltd, 1 Science Park Road, #05-09 The Capricorn, Singapore Science Park II, Singapore 117528, Singapore.
authors.forename: Haishan
authors.initials: H
authors.lastname: Wang
authors.forename: Niefang
authors.initials: N
authors.lastname: Yu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Song
authors.forename: Dizhong
authors.initials: D
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Zou
authors.forename: Weiping
authors.initials: W
authors.lastname: Deng
authors.forename: Pek Ling
authors.initials: PL
authors.lastname: Lye
authors.forename: Joyce
authors.initials: J
authors.lastname: Chang
authors.forename: Melvin
authors.initials: M
authors.lastname: Ng
authors.forename: Eric T
authors.initials: ET
authors.lastname: Sun
authors.forename: Kanda
authors.initials: K
authors.lastname: Sangthongpitag
authors.forename: Xukun
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wu
authors.forename: Hwee Hoon
authors.initials: HH
authors.lastname: Khng
authors.forename: Lijuan
authors.initials: L
authors.lastname: Fang
authors.forename: Siok Kun
authors.initials: SK
authors.lastname: Goh
authors.forename: Wai Chung
authors.initials: WC
authors.lastname: Ong
authors.forename: Zahid
authors.initials: Z
authors.lastname: Bonday
authors.forename: Walter
authors.initials: W
authors.lastname: Stünkel
authors.forename: Anders
authors.initials: A
authors.lastname: Poulsen
authors.forename: Michael
authors.initials: M
authors.lastname: Entzeroth
mesh_terms: D000178:Acrylamides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases