title: Thyroid receptor ligands. Part 5: novel bicyclic agonist ligands selective for the thyroid hormone receptor beta.
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.
authors.affiliation: Karo Bio AB, Novum, Huddinge SE-141 57, Sweden.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Garcia Collazo
authors.forename: Konrad F
authors.initials: KF
authors.lastname: Koehler
authors.forename: Neeraj
authors.initials: N
authors.lastname: Garg
authors.forename: Mathias
authors.initials: M
authors.lastname: Färnegårdh
authors.forename: Bolette
authors.initials: B
authors.lastname: Husman
authors.forename: Liu
authors.initials: L
authors.lastname: Ye
authors.forename: Jan
authors.initials: J
authors.lastname: Ljunggren
authors.forename: Karin
authors.initials: K
authors.lastname: Mellström
authors.forename: Johnny
authors.initials: J
authors.lastname: Sandberg
authors.forename: Marlena
authors.initials: M
authors.lastname: Grynfarb
authors.forename: Harri
authors.initials: H
authors.lastname: Ahola
authors.forename: Johan
authors.initials: J
authors.lastname: Malm
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D003500:Cyclization; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D051381:Rats; D013379:Substrate Specificity; D037042:Thyroid Hormone Receptors beta / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism*; D013974:Thyroxine / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D007211:Indoles; D008024:Ligands; D037042:Thyroid Hormone Receptors beta; D013974:Thyroxine