TY - JOUR
T1 - 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
AU - Woo, L.W.L.
AU - Wood, P.M.
AU - Bubert, C.
AU - Thomas, M.P.
AU - Purohit, A.
AU - Potter, B.V.L.
PY - 2013/5
Y1 - 2013/5
N2 - 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 invitro DASI discovered is an imidazole derivative with IC50 values against aromatase and steroid sulfatase in a JEG-3 cell preparation of 0.2 and 2.5nM, respectively. The parent phenol of this compound inhibits aromatase with an IC value of 0.028nM in the same assay.
AB - 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 invitro DASI discovered is an imidazole derivative with IC50 values against aromatase and steroid sulfatase in a JEG-3 cell preparation of 0.2 and 2.5nM, respectively. The parent phenol of this compound inhibits aromatase with an IC value of 0.028nM in the same assay.
UR - http://www.scopus.com/inward/record.url?scp=84877074103&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1002/cmdc.201300015
U2 - 10.1002/cmdc.201300015
DO - 10.1002/cmdc.201300015
M3 - Article
AN - SCOPUS:84877074103
SN - 1860-7179
VL - 8
SP - 779
EP - 799
JO - ChemMedChem
JF - ChemMedChem
IS - 5
ER -