Design, synthesis, and structure-activity relationship (SAR) of N-[7-(4-hydroxyphenoxy)-6-methylindan-4-yl]malonamic
Hiroaki Shiohara1, Tetsuya Nakamura, Norihiko Kikuchi
1Central Research Laboratory, Kissei Pharmaceutical Co., Ltd, 4365-1, Kashiwabara, Hotaka, Azumino-city, Nagano 399-8304, Japan. hiroaki_shiohara@pharm.kissei.co.jp
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.
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