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

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

Faculty of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

51 Citations (Scopus)

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.

Original language	English
Pages (from-to)	4427-4431
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	20
DOIs	https://doi.org/10.1016/j.bmcl.2005.07.048
Publication status	Published - Oct 15 2005

Keywords

HDAC inhibitor
Phthalimide
Thalidomide

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2005.07.048

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title = "Design and synthesis of phthalimide-type histone deacetylase inhibitors",

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.",

keywords = "HDAC inhibitor, Phthalimide, Thalidomide",

author = "Chihiro Shinji and Takanori Nakamura and Satoko Maeda and Minoru Yoshida and Yuichi Hashimoto and Hiroyuki Miyachi",

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AU - Shinji, Chihiro

AU - Nakamura, Takanori

AU - Maeda, Satoko

AU - Yoshida, Minoru

AU - Hashimoto, Yuichi

AU - Miyachi, Hiroyuki

N1 - Funding Information: The authors thank Screening Committee of New Anticancer Agents supported by Grant-in-Aid for Scientific Research on Priority Area ‘Cancer’ from The Ministry of Education, Culture, Sports, Science and Technology, Japan. The work described in this paper was partially supported by a Grant-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology, Japan.

PY - 2005/10/15

Y1 - 2005/10/15

N2 - 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.

AB - 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.

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KW - Phthalimide

KW - Thalidomide

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Design and synthesis of phthalimide-type histone deacetylase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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