Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors
© The Royal Society of Chemistry 2018. 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)...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
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Royal Society of Chemistry
2018
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| Online Access: | http://hdl.handle.net/20.500.11937/65805 |
| _version_ | 1848761207716052992 |
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| author | Shi, Y. Wu, Y. Su, M. Shen, D. Gunosewoyo, Hendra Yang, F. Li, J. Tang, J. Zhou, Y. Yu, L. |
| author_facet | Shi, Y. Wu, Y. Su, M. Shen, D. Gunosewoyo, Hendra Yang, F. Li, J. Tang, J. Zhou, Y. Yu, L. |
| author_sort | Shi, Y. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © The Royal Society of Chemistry 2018. 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. |
| first_indexed | 2025-11-14T10:28:00Z |
| format | Journal Article |
| id | curtin-20.500.11937-65805 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:28:00Z |
| publishDate | 2018 |
| publisher | Royal Society of Chemistry |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-658052019-07-08T06:40:35Z Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors Shi, Y. Wu, Y. Su, M. Shen, D. Gunosewoyo, Hendra Yang, F. Li, J. Tang, J. Zhou, Y. Yu, L. © The Royal Society of Chemistry 2018. 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/65805 10.1039/c7ra13097j http://creativecommons.org/licenses/by/3.0/ Royal Society of Chemistry fulltext |
| spellingShingle | Shi, Y. Wu, Y. Su, M. Shen, D. Gunosewoyo, Hendra Yang, F. Li, J. Tang, J. Zhou, Y. Yu, L. Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors |
| title | Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors |
| title_full | Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors |
| title_fullStr | Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors |
| title_full_unstemmed | Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors |
| title_short | Novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (LSD1) inhibitors |
| title_sort | novel spirocyclic tranylcypromine derivatives as lysine-specific demethylase 1 (lsd1) inhibitors |
| url | http://hdl.handle.net/20.500.11937/65805 |