title: Design, synthesis, and structure-activity relationship (SAR) of N-[7-(4-hydroxyphenoxy)-6-methylindan-4-yl]malonamic acids as thyroid hormone receptor β (TRβ) selective agonists.
abstract: Highly TRβ selective thyromimetics have several potential therapeutic applications. Based on the novel indane derivative KTA-439 with high receptor (TRβ) and organ (liver) selectivity, a series of thyroid hormone analogues were prepared, in which the isopropyl at the 3'-position was replaced with alkyl and aralkyl moieties of variable lengths and branches. Binding assays for these human TRs and reporter cell assays showed that 2-arylethyl derivatives had higher TRβ selectivity than KTA-439. KTA-574, a representative 2-arylethyl derivative, had TRβ specificity in a binding assay and exhibited full agonism in a reporter cell assay.
authors.affiliation: Central Research Laboratory, Kissei Pharmaceutical Co., Ltd, 4365-1, Kashiwabara, Hotaka, Azumino-city, Nagano 399-8304, Japan. hiroaki_shiohara@pharm.kissei.co.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiohara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kikuchi
authors.forename: Tomonaga
authors.initials: T
authors.lastname: Ozawa
authors.forename: Akane
authors.initials: A
authors.lastname: Matsuzawa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nagano
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohnota
authors.forename: Takahide
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hashizume
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008314:Malonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D037042:Thyroid Hormone Receptors beta / Q000819:agonists*
chemical_list: D008314:Malonates; D037042:Thyroid Hormone Receptors beta; C013098:malonamic acid