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

Hanae Benelkebir; Christopher Hodgkinson; Patrick J. Duriez; Annette L. Hayden; Rosemary A. Bulleid; Simon J. Crabb; Graham Packham; A Ganesan

doi:10.1016/j.bmc.2011.02.017

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

Hanae Benelkebir, Christopher Hodgkinson, Patrick J. Duriez, Annette L. Hayden, Rosemary A. Bulleid, Simon J. Crabb, Graham Packham, A Ganesan

Research output: Contribution to journal › Article › peer-review

84 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3709-3716
Number of pages	8
Journal	Bioorganic & Medicinal Chemistry
Volume	19
Issue number	12
DOIs	https://doi.org/10.1016/j.bmc.2011.02.017
Publication status	Published - 15 Jun 2011

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10.1016/j.bmc.2011.02.017

Cite this

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title = "Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors",

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.",

author = "Hanae Benelkebir and Christopher Hodgkinson and Duriez, {Patrick J.} and Hayden, {Annette L.} and Bulleid, {Rosemary A.} and Crabb, {Simon J.} and Graham Packham and A Ganesan",

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T1 - Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors

AU - Benelkebir, Hanae

AU - Hodgkinson, Christopher

AU - Duriez, Patrick J.

AU - Hayden, Annette L.

AU - Bulleid, Rosemary A.

AU - Crabb, Simon J.

AU - Packham, Graham

AU - Ganesan, A

PY - 2011/6/15

Y1 - 2011/6/15

N2 - 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.

AB - 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.

U2 - 10.1016/j.bmc.2011.02.017

DO - 10.1016/j.bmc.2011.02.017

M3 - Article

VL - 19

SP - 3709

EP - 3716

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

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ER -