Thyroid receptor ligands. Part 7: Indirect antagonists of the thyroid hormone receptor with improved affinity.
Based on the concept of 'indirect antagonism' of nuclear receptors, a series of thyroid hormone receptor (TR) antagonists were prepared with improved affinity compared with what was previously described. The results of a binding assay for the human TR and reporter cell assay revealed, within this series, that an m-bromobenzoyl substituent (11f) was optimal in terms of affinity and antagonist activity. Compared with already reported TR antagonists, their affinities are within the same range, thus potentially representing useful approach to novel and high-affinity TR-antagonists.
Malm
Johan
J
Karo Bio AB, Novum, Huddinge S-141 57, Sweden. johanm@excite.com
Gordon
Sandra
S
Brandt
Peter
P
Carlsson
Bo
B
Agback
Peter
P
Bäckbro Saeidi
Anna
A
Sandberg
Johnny
J
D001965:Bromides / Q000138:chemical synthesis*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D011485:Protein Binding; D020033:Protein Isoforms; D013329:Structure-Activity Relationship; D037021:Thyroid Hormone Receptors alpha / Q000037:antagonists & inhibitors* / Q000737:chemistry; D037042:Thyroid Hormone Receptors beta / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015533:Transcriptional Activation
D001965:Bromides; D008024:Ligands; D020033:Protein Isoforms; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta