title: Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors.
abstract: Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. A mercaptoamide functionality was designed as a bidentate zinc chelator and incorporated into the hydroxamic acid based SAHA (1) scaffold in order to identify non-hydroxamate compounds as potential inhibitors of histone deacetylases. Two sets of mercaptoamides 2 and 3 with varying spacer length were synthesized and their HDAC inhibitory activity was evaluated. Low micromolar inhibition was observed for mercaptoamides 2e, 3b, and 3d.
authors.affiliation: Miikana Therapeutics Inc, 6519 Dumbarton Circle, Fremont, CA 94555, USA. skumar@miikana.com <skumar@miikana.com>
authors.forename: Sampath-Kumar
authors.initials: SK
authors.lastname: Anandan
authors.forename: John S
authors.initials: JS
authors.lastname: Ward
authors.forename: Richard D
authors.initials: RD
authors.lastname: Brokx
authors.forename: Mark R
authors.initials: MR
authors.lastname: Bray
authors.forename: Dinesh V
authors.initials: DV
authors.lastname: Patel
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Xiao
mesh_terms: D000577:Amides / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000145:classification* / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013438:Sulfhydryl Compounds