title: Thyroid receptor ligands. Part 7: Indirect antagonists of the thyroid hormone receptor with improved affinity.
abstract: 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.
authors.affiliation: Karo Bio AB, Novum, Huddinge S-141 57, Sweden. johanm@excite.com
authors.forename: Johan
authors.initials: J
authors.lastname: Malm
authors.forename: Sandra
authors.initials: S
authors.lastname: Gordon
authors.forename: Peter
authors.initials: P
authors.lastname: Brandt
authors.forename: Bo
authors.initials: B
authors.lastname: Carlsson
authors.forename: Peter
authors.initials: P
authors.lastname: Agback
authors.forename: Anna
authors.initials: A
authors.lastname: Bäckbro Saeidi
authors.forename: Johnny
authors.initials: J
authors.lastname: Sandberg
mesh_terms: 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
chemical_list: D001965:Bromides; D008024:Ligands; D020033:Protein Isoforms; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta