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Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors

Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors
Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors
Asymmetric cyclopropanation of styrenes by tert-butyl diazoacetate followed by ester hydrolysis and Curtius rearrangement gave a series of tranylcypromine analogues as single enantiomers. The o,- m- and p-bromo analogues were all more active than tranylcypromine in a LSD1 enzyme assay. The m- and p-bromo analogues were micromolar growth inhibitors of the LNCaP prostate cancer cell line as were the corresponding biphenyl analogues prepared from the bromide by Suzuki crosscoupling.
epigenetics, prostate cancer, lysine demethylase, enzyme inhibitors
0968-0896
Benelkebir, Hanae
6b4a6913-02de-4700-aba3-939968130c51
Hodgkinson, Christopher
3eb04933-369d-460e-a0e0-b36b322d1e9b
Duriez, Patrick J.
4cf499bc-007a-43b3-b180-d6e5dc3d151b
Hayden, Annette L.
80301564-d83f-404c-abd0-0f8acf6c2e60
Bulleid, Rosemary A.
b8f023d3-dae8-4226-b4e9-c30e2ad35199
Crabb, Simon J.
bcd1b566-7677-4f81-8429-3ab0e85f8373
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Ganesan, A.
62aa5a87-9308-4383-8686-99726b6bcfb9
Benelkebir, Hanae
6b4a6913-02de-4700-aba3-939968130c51
Hodgkinson, Christopher
3eb04933-369d-460e-a0e0-b36b322d1e9b
Duriez, Patrick J.
4cf499bc-007a-43b3-b180-d6e5dc3d151b
Hayden, Annette L.
80301564-d83f-404c-abd0-0f8acf6c2e60
Bulleid, Rosemary A.
b8f023d3-dae8-4226-b4e9-c30e2ad35199
Crabb, Simon J.
bcd1b566-7677-4f81-8429-3ab0e85f8373
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Ganesan, A.
62aa5a87-9308-4383-8686-99726b6bcfb9

Benelkebir, Hanae, Hodgkinson, Christopher, Duriez, Patrick J., Hayden, Annette L., Bulleid, Rosemary A., Crabb, Simon J., Packham, Graham and Ganesan, A. (2011) Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors. Bioorganic & Medicinal Chemistry. (doi:10.1016/j.bmc.2011.02.017). (PMID:21382717)

Record type: Article

Abstract

Asymmetric cyclopropanation of styrenes by tert-butyl diazoacetate followed by ester hydrolysis and Curtius rearrangement gave a series of tranylcypromine analogues as single enantiomers. The o,- m- and p-bromo analogues were all more active than tranylcypromine in a LSD1 enzyme assay. The m- and p-bromo analogues were micromolar growth inhibitors of the LNCaP prostate cancer cell line as were the corresponding biphenyl analogues prepared from the bromide by Suzuki crosscoupling.

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More information

Published date: 13 February 2011
Keywords: epigenetics, prostate cancer, lysine demethylase, enzyme inhibitors

Identifiers

Local EPrints ID: 180129
URI: http://eprints.soton.ac.uk/id/eprint/180129
ISSN: 0968-0896
PURE UUID: 61fb91ad-5748-4b58-9f42-b0ed549c2eb0
ORCID for Patrick J. Duriez: ORCID iD orcid.org/0000-0003-1814-2552
ORCID for Simon J. Crabb: ORCID iD orcid.org/0000-0003-3521-9064
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 06 Apr 2011 09:20
Last modified: 15 Mar 2024 03:16

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Contributors

Author: Hanae Benelkebir
Author: Christopher Hodgkinson
Author: Patrick J. Duriez ORCID iD
Author: Annette L. Hayden
Author: Rosemary A. Bulleid
Author: Simon J. Crabb ORCID iD
Author: Graham Packham ORCID iD
Author: A. Ganesan

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