Design and synthesis of phthalimide-type histone deacetylase inhibitors

Chihiro Shinji; Takanori Nakamura; Satoko Maeda; Minoru Yoshida; Yuichi Hashimoto; Hiroyuki Miyachi

doi:10.1016/j.bmcl.2005.07.048

Design and synthesis of phthalimide-type histone deacetylase inhibitors

Bioorg Med Chem Lett. 2005 Oct 15;15(20):4427-31. doi: 10.1016/j.bmcl.2005.07.048.

Authors

Chihiro Shinji¹, Takanori Nakamura, Satoko Maeda, Minoru Yoshida, Yuichi Hashimoto, Hiroyuki Miyachi

Affiliation

¹ Institute of Molecular and Cellular Biosciences, The University of Tokyo Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

PMID: 16137884
DOI: 10.1016/j.bmcl.2005.07.048

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Histone Deacetylase Inhibitors*
Phthalimides / chemical synthesis
Phthalimides / chemistry*
Phthalimides / pharmacology
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Histone Deacetylase Inhibitors
Phthalimides