Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors.
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.
Anandan
Sampath-Kumar
SK
Miikana Therapeutics Inc, 6519 Dumbarton Circle, Fremont, CA 94555, USA. skumar@miikana.com <skumar@miikana.com>
Ward
John S
JS
Brokx
Richard D
RD
Bray
Mark R
MR
Patel
Dinesh V
DV
Xiao
Xiao-Xi
XX
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*
D000577:Amides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013438:Sulfhydryl Compounds