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Synthesis and Structure–Activity Relationship Studies of Derivatives of the Dual Aromatase–Sulfatase Inhibitor 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate

4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (F, Cl, Br) derivatives are first-generation dual aromatase and sulfatase inhibitors (DASIs). Structure–activity relationship studies were performed on these compounds, and various modifications were ma...

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Autores principales: Woo, L W Lawrence, Wood, Paul M, Bubert, Christian, Thomas, Mark P, Purohit, Atul, Potter, Barry V L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743159/
https://www.ncbi.nlm.nih.gov/pubmed/23495205
http://dx.doi.org/10.1002/cmdc.201300015
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author Woo, L W Lawrence
Wood, Paul M
Bubert, Christian
Thomas, Mark P
Purohit, Atul
Potter, Barry V L
author_facet Woo, L W Lawrence
Wood, Paul M
Bubert, Christian
Thomas, Mark P
Purohit, Atul
Potter, Barry V L
author_sort Woo, L W Lawrence
collection PubMed
description 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (F, Cl, Br) derivatives are first-generation dual aromatase and sulfatase inhibitors (DASIs). Structure–activity relationship studies were performed on these compounds, and various modifications were made to their structures involving relocation of the halogen atom, introduction of more halogen atoms, replacement of the halogen with another group, replacement of the methylene linker with a difluoromethylene linker, replacement of the para-cyanophenyl ring with other ring structures, and replacement of the triazolyl group with an imidazolyl group. The most potent in vitro DASI discovered is an imidazole derivative with IC(50) values against aromatase and steroid sulfatase in a JEG-3 cell preparation of 0.2 and 2.5 nm, respectively. The parent phenol of this compound inhibits aromatase with an IC(50) value of 0.028 nm in the same assay.
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spelling pubmed-37431592013-08-15 Synthesis and Structure–Activity Relationship Studies of Derivatives of the Dual Aromatase–Sulfatase Inhibitor 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate Woo, L W Lawrence Wood, Paul M Bubert, Christian Thomas, Mark P Purohit, Atul Potter, Barry V L ChemMedChem Full Papers 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (F, Cl, Br) derivatives are first-generation dual aromatase and sulfatase inhibitors (DASIs). Structure–activity relationship studies were performed on these compounds, and various modifications were made to their structures involving relocation of the halogen atom, introduction of more halogen atoms, replacement of the halogen with another group, replacement of the methylene linker with a difluoromethylene linker, replacement of the para-cyanophenyl ring with other ring structures, and replacement of the triazolyl group with an imidazolyl group. The most potent in vitro DASI discovered is an imidazole derivative with IC(50) values against aromatase and steroid sulfatase in a JEG-3 cell preparation of 0.2 and 2.5 nm, respectively. The parent phenol of this compound inhibits aromatase with an IC(50) value of 0.028 nm in the same assay. WILEY-VCH Verlag 2013-05 2013-03-11 /pmc/articles/PMC3743159/ /pubmed/23495205 http://dx.doi.org/10.1002/cmdc.201300015 Text en Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Full Papers
Woo, L W Lawrence
Wood, Paul M
Bubert, Christian
Thomas, Mark P
Purohit, Atul
Potter, Barry V L
Synthesis and Structure–Activity Relationship Studies of Derivatives of the Dual Aromatase–Sulfatase Inhibitor 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate
title Synthesis and Structure–Activity Relationship Studies of Derivatives of the Dual Aromatase–Sulfatase Inhibitor 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate
title_full Synthesis and Structure–Activity Relationship Studies of Derivatives of the Dual Aromatase–Sulfatase Inhibitor 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate
title_fullStr Synthesis and Structure–Activity Relationship Studies of Derivatives of the Dual Aromatase–Sulfatase Inhibitor 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate
title_full_unstemmed Synthesis and Structure–Activity Relationship Studies of Derivatives of the Dual Aromatase–Sulfatase Inhibitor 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate
title_short Synthesis and Structure–Activity Relationship Studies of Derivatives of the Dual Aromatase–Sulfatase Inhibitor 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate
title_sort synthesis and structure–activity relationship studies of derivatives of the dual aromatase–sulfatase inhibitor 4-{[(4-cyanophenyl)(4h-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743159/
https://www.ncbi.nlm.nih.gov/pubmed/23495205
http://dx.doi.org/10.1002/cmdc.201300015
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