Design and synthesis of aryl ether and sulfone hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.
A series of novel hydroxamic acid based histone deacetylases (HDAC) inhibitors with aryl ether and aryl sulfone residues at the terminus of a substituted, unsaturated 5-carbon spacer moiety have been synthesized for the first time and evaluated. Compounds with meta- and para-substitution on the aryl ring of ether hydroxamic acids 19c, 20c, 19e, 19f and 19g are potent HDAC inhibitors with activities at low nanomolar levels.
AMRI, Medicinal Chemistry Department, 30 Corporate Circle, PO Box 15098, Albany, NY 12212, USA. brian.gregg@amriglobal.com
Chittari
C
Pabba
Brian T
BT
Gregg
Douglas B
DB
Kitchen
Zhen Jia
ZJ
Chen
Angela
A
Judkins
D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D004987:Ethers / Q000737:chemistry*; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry*
D004987:Ethers; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013450:Sulfones; D006655:Histone Deacetylases