Synthesis of sulfonamides and evaluation of their histone deacetylase (HDAC) activity.
A simple synthesis of sulfonamides 4-22 as novel histone deacetylase (HDAC) inhibitors is described. The key synthetic strategies involve N-sulfonylation of L-proline benzyl ester hydrochloride (2) and coupling reaction of N-sulfonyl chloride 3 with amines in high yields. It was found that several compounds showed good cellular potency with the most potent compound 20 exhibiting an IC50 = 2.8 microM in vitro.
Oh
Seikwan
S
Department of Neuroscience and Medical Research Institute, College of Medicine, Ewha Womans University, Seoul 158-710, South Korea.
Moon
Hyung-In
HI
Son
Il-Hong
IH
Jung
Jae-Chul
JC
Avery
Mitchell A
MA
D045744:Cell Line, Tumor; D002855:Chromatography, Thin Layer; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D013449:Sulfonamides