TY - JOUR
T1 - Inhibitors of the interaction of a thyroid hormone receptor and coactivators
T2 - Preliminary structure-activity relationships
AU - Arnold, Leggy A.
AU - Kosinski, Aaron
AU - Estébanez-Perpiñá, Eva
AU - Fletterick, Robert J.
AU - Guy, R. Kiplin
PY - 2007/11/1
Y1 - 2007/11/1
N2 - The modulation of gene regulation by blocking the interaction between the thyroid receptor (TR) and obligate coregulators has been reported recently with the discovery of the lead compound 3-(dimethylamino)-1-(4-hexylphenyl)propan-1- one). Herein we report studies aimed at optimization of this initial hit to determine the basic parameters of the structure-activity relationships and clarify the mechanism of action. These studies provided new insights, showing that activity and TRβ isoform selectivity is highly correlated with the structural composition of these covalent inhibitors.
AB - The modulation of gene regulation by blocking the interaction between the thyroid receptor (TR) and obligate coregulators has been reported recently with the discovery of the lead compound 3-(dimethylamino)-1-(4-hexylphenyl)propan-1- one). Herein we report studies aimed at optimization of this initial hit to determine the basic parameters of the structure-activity relationships and clarify the mechanism of action. These studies provided new insights, showing that activity and TRβ isoform selectivity is highly correlated with the structural composition of these covalent inhibitors.
UR - https://www.scopus.com/pages/publications/35848969820
UR - https://www.scopus.com/pages/publications/35848969820#tab=citedBy
U2 - 10.1021/jm070556y
DO - 10.1021/jm070556y
M3 - Article
C2 - 17918822
AN - SCOPUS:35848969820
SN - 0022-2623
VL - 50
SP - 5269
EP - 5280
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 22
ER -