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新型螺环反苯环丙胺衍生物作为赖氨酸特异性去甲基化酶1（LSD1）抑制剂

Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors.

作者信息

Shi Ying, Wu Yan-Ran, Su Ming-Bo, Shen Dong-Hao, Gunosewoyo Hendra, Yang Fan, Li Jia, Tang Jie, Zhou Yu-Bo, Yu Li-Fang

机构信息

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University 3663 North Zhongshan Road Shanghai 200062 China

CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences 189 Guo Shou Jing Road Shanghai 201203 China

出版信息

RSC Adv. 2018 Jan 5;8(3):1666-1676. doi: 10.1039/c7ra13097j. eCollection 2018 Jan 2.

DOI:10.1039/c7ra13097j
PMID:35540911
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9077246/
Abstract

Herein we describe the design, synthesis, and biological evaluation of a novel series of tranylcypromine-based LSD1 inhibitors conformational restriction using spiro ring systems. A simple, direct spirocyclic analog of tranylcypromine (compounds 8a and 8b) was shown to be a 28- to 129-fold more potent inhibitor of LSD1 enzyme compared to tranylcypromine. Further incorporation of various substituted benzyl groups to the amino group resulted in a suite of 2',3'-dihydrospiro[cyclopropane-1,1'-inden]-2-amines that are potent LSD1 inhibitors with excellent selectivity profiles (14a, 15b, 16a, 19a and 20b) against closely related enzymes such as MAO-A, MAO-B, and LSD2.

摘要

在此，我们描述了一系列基于反苯环丙胺的新型LSD1抑制剂的设计、合成及生物学评价，这些抑制剂利用螺环系统进行构象限制。与反苯环丙胺相比，一种简单、直接的反苯环丙胺螺环类似物（化合物8a和8b）对LSD1酶的抑制活性高28至129倍。在氨基上进一步引入各种取代苄基，得到了一系列2',3'-二氢螺[环丙烷-1,1'-茚]-2-胺，它们是强效的LSD1抑制剂，对密切相关的酶如MAO-A、MAO-B和LSD2具有优异的选择性（14a、15b、16a、19a和20b）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/b2965d50740b/c7ra13097j-s3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/acb98cc26b61/c7ra13097j-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/29a463b4a8be/c7ra13097j-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/6ccd563764a5/c7ra13097j-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/aa409a1b0cb4/c7ra13097j-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/35c71c3de0be/c7ra13097j-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/b2965d50740b/c7ra13097j-s3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/acb98cc26b61/c7ra13097j-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/29a463b4a8be/c7ra13097j-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/6ccd563764a5/c7ra13097j-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/aa409a1b0cb4/c7ra13097j-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/35c71c3de0be/c7ra13097j-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/186c/9077246/b2965d50740b/c7ra13097j-s3.jpg

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2
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3
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ACS Med Chem Lett. 2020 May 6;11(6):1213-1220. doi: 10.1021/acsmedchemlett.0c00060. eCollection 2020 Jun 11.
4
Investigating the Binding Mode of Reversible LSD1 Inhibitors Derived from Stilbene Derivatives by 3D-QSAR, Molecular Docking, and Molecular Dynamics Simulation.通过 3D-QSAR、分子对接和分子动力学模拟研究源于二苯乙烯衍生物的可逆 LSD1 抑制剂的结合模式。
Molecules. 2019 Dec 6;24(24):4479. doi: 10.3390/molecules24244479.
J Med Chem. 2016 Jan 14;59(1):253-263. doi: 10.1021/acs.jmedchem.5b01361. Epub 2015 Dec 24.
4
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Curr Opin Pharmacol. 2015 Aug;23:52-60. doi: 10.1016/j.coph.2015.05.009. Epub 2015 Jun 5.
5
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Bioorg Med Chem Lett. 2014 Aug 15;24(16):3673-82. doi: 10.1016/j.bmcl.2014.06.081. Epub 2014 Jul 5.
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