Design, synthesis, and structure-activity relationship (SAR) of N-[7-(4-hydroxyphenoxy)-6-methylindan-4-yl]malonamic acids as thyroid hormone receptor beta (TRbeta) selective agonists.

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Shiohara H, Nakamura T, Kikuchi N, Ozawa T, Matsuzawa A, Nagano R, Ohnota H, Miyamoto T, Ichikawa K, Hashizume K

Design, synthesis, and structure-activity relationship (SAR) of N-[7-(4-hydroxyphenoxy)-6-methylindan-4-yl]malonamic acids as thyroid hormone receptor beta (TRbeta) selective agonists.

Bioorg Med Chem. 2013 Feb 1;21(3):592-607. doi: 10.1016/j.bmc.2012.12.002. Epub 2012 Dec 11.

PubMed ID

23276448 [ View in PubMed

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Abstract

Highly TRbeta selective thyromimetics have several potential therapeutic applications. Based on the novel indane derivative KTA-439 with high receptor (TRbeta) 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 TRbeta selectivity than KTA-439. KTA-574, a representative 2-arylethyl derivative, had TRbeta specificity in a binding assay and exhibited full agonism in a reporter cell assay.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Liothyronine	Thyroid hormone receptor alpha	Ki (nM)	2.3	N/A	N/A	Details
Liothyronine	Thyroid hormone receptor beta	Ki (nM)	2.3	N/A	N/A	Details