Abstract
Based on the examination of the crystal structure of rat TRbeta complexed with 3,5,3'-triiodo-l-thyronine (2) a novel TRbeta-selective indole derivative 6b was prepared and tested in vitro. This compound was found to be 14 times selective for TRbeta over TRalpha in binding and its beta-selectivity could be rationalized through the comparison of the X-ray crystallographic structures of 6b complexed with TRalpha and TRbeta.
MeSH terms
-
Animals
-
Crystallography, X-Ray
-
Cyclization
-
Humans
-
Indoles / chemistry*
-
Indoles / metabolism
-
Indoles / pharmacology*
-
Inhibitory Concentration 50
-
Ligands
-
Molecular Structure
-
Rats
-
Substrate Specificity
-
Thyroid Hormone Receptors beta / agonists*
-
Thyroid Hormone Receptors beta / chemistry
-
Thyroid Hormone Receptors beta / metabolism*
-
Thyroxine / chemical synthesis
-
Thyroxine / chemistry
Substances
-
Indoles
-
Ligands
-
Thyroid Hormone Receptors beta
-
Thyroxine