Thyroid receptor ligands. 3. Design and synthesis of 3,5-dihalo-4-alkoxyphenylalkanoic acids as indirect antagonists of the thyroid hormone receptor.
Based on the recently described concept of "indirect antagonism" of nuclear receptors, a series of thyroid hormone receptor (TR) antagonists were prepared, in which the outer ring of a thyromimetic was replaced with alkyl chains of variable length and branch. The results of a binding assay for the human TR and reporter cell assay revealed, within this series, a positive correlation between increasing bulk of the alkyl group and affinity to TRs. Compared with already reported TR antagonists, their affinities are within the same range, thus potentially representing a useful approach to novel and high affinity TR-antagonists.
Hedfors
Asa
A
Karo Bio AB, Novum, Huddinge SE-141 57, Sweden.
Appelqvist
Theresa
T
Carlsson
Bo
B
Bladh
Lars-Göran
LG
Litten
Chris
C
Agback
Peter
P
Grynfarb
Marlena
M
Koehler
Konrad F
KF
Malm
Johan
J
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017930:Genes, Reporter; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D010636:Phenols / Q000737:chemistry; D017433:Protein Structure, Secondary; D011869:Radioligand Assay; D051381:Rats; D013329:Structure-Activity Relationship; D037021:Thyroid Hormone Receptors alpha / Q000037:antagonists & inhibitors* / Q000737:chemistry; D037042:Thyroid Hormone Receptors beta / Q000037:antagonists & inhibitors* / Q000737:chemistry
D004987:Ethers; D008024:Ligands; D010636:Phenols; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta