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Issue 3, 2018
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Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors

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Abstract

Herein we describe the design, synthesis, and biological evaluation of a novel series of tranylcypromine-based LSD1 inhibitors via 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 (e.g.14a, 15b, 16a, 19a and 20b) against closely related enzymes such as MAO-A, MAO-B, and LSD2.

Graphical abstract: Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors

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Supplementary files

Article information


Submitted
06 Dec 2017
Accepted
21 Dec 2017
First published
05 Jan 2018

This article is Open Access

RSC Adv., 2018,8, 1666-1676
Article type
Paper

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

Y. Shi, Y. Wu, M. Su, D. Shen, H. Gunosewoyo, F. Yang, J. Li, J. Tang, Y. Zhou and L. Yu, RSC Adv., 2018, 8, 1666
DOI: 10.1039/C7RA13097J

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