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CC BY 4.0 · Pharmaceutical Fronts 2023; 05(02): e91-e100
DOI: 10.1055/s-0043-1768613
Original Article

Synthesis and Crystal Structure Analysis of Histone Deacetylase Inhibitor Chidamide

Bo Han   #
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Xin-Yan Peng   #
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Yan-Qing Gong
2   State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Jia-Liang Zhong
2   State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Qing-Wei Zhang
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
› Institutsangaben Funding We gratefully acknowledge financial support from the National Science and Technology Major Project (Grant No. 2018ZX09711002-002-009), the National Natural Science Foundation of China (Grant No. 81703358), Science and Technology Commission of Shanghai Municipality (Grant No. 17431903900, 18QB1404200, 21S11908000, and 22ZR1460300), and Graduate Innovation Fund Project of China State Institute of Pharmaceutical Industry (Grant No. YJS2021013 and YJS2021011).
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Abstract

Chidamide is the first oral subtype-selective histone deacetylase inhibitor approved in China for the treatment of relapsed and refractory peripheral T cell lymphoma. Due to the existence of isomers, many articles or patents have mistaken its structure. Herein we explored the synthesis of the key intermediate (E)-4-((3-(pyridin-3-yl)acrylamido)methyl)benzoic acid (A-3) and chidamide, using the condensing agent HBTU, instead of the unstable N,N'-carbonyldiimidazole. The single crystal of chidamide was determined by X-ray diffraction study. The optimized preparation process was easy to operate, and the purity of the final product can be up to 99.76%. Moreover, the structure of chidamide was established to be (E)-N-(2-amino-4-fluorophenyl)-4-((3-(pyridin-3-yl)acrylamido)methyl)benzamide.

Keywords

histone deacetylase - chidamide - synthesis - HBTU - single crystal

# These authors contributed equally to this work.




Publikationsverlauf

Eingereicht: 03. September 2022

Angenommen: 31. März 2023

Artikel online veröffentlicht:
24. Mai 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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