Design and synthesis of phthalimide-type histone deacetylase inhibitors.
Several hydroxamic acid derivatives with a substituted phthalimide group as a linker and/or cap structure, prepared during structural development studies based on thalidomide, were found to have histone deacetylase (HDAC)-inhibitory activity. Structure-activity relationship studies indicated that nature of the substituent introduced at the phthalimide nitrogen atom, introduction of a hydroxamic acid structure, and distance between the N-hydroxyl group and the cap structure are important for HDAC-inhibitory activity.
Shinji
Chihiro
C
Institute of Molecular and Cellular Biosciences, The University of Tokyo Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Nakamura
Takanori
T
Maeda
Satoko
S
Yoshida
Minoru
M
Hashimoto
Yuichi
Y
Miyachi
Hiroyuki
H
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D010797:Phthalimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010797:Phthalimides