Synthesis of ligands for nuclear receptors of thyroid hormones

Synthesis of ligands for nuclear receptors of thyroid hormones

Castro, Guilherme V. de; Sanches, Vitor Lacerda; Donate, Paulo M.; Polikarpov, Igor; Sairre, Mirela I. de

Abstract:

The thyroid hormones (TH) (Figure 1), thyroxine (T4) and triiodo L-thyronine (T3), influence growth, development and homeostasis, with important effects on general metabolism, lipid levels, heart rate and mood. Pharmacologic thyroid hormone treatment could be used to combat obesity, lower cholesterol and triglyceride levels but fails in practice because of associated symptoms of hyperthyroidism, in particular, elevated heart rate and arrhythmia. The TH effects are mediated by the thyroid hormone receptors (TRs), transcription factors that bind to DNA via specific sequences, in promoters of target genes. The TRs are present in cells in two isoforms, TRα and TRβ, and several lines of evidence showed that the development of ligands that bind to TRβ could lead to safer therapies for the disorders cited above. In this work, we report a synthetic route, shown in scheme 1, which allows the obtaining of two new ligands to TRs planned by structure-activity relationship (SAR) studies.

The thyroid hormones (TH) (Figure 1), thyroxine (T4) and triiodo L-thyronine (T3), influence growth, development and homeostasis, with important effects on general metabolism, lipid levels, heart rate and mood. Pharmacologic thyroid hormone treatment could be used to combat obesity, lower cholesterol and triglyceride levels but fails in practice because of associated symptoms of hyperthyroidism, in particular, elevated heart rate and arrhythmia. The TH effects are mediated by the thyroid hormone receptors (TRs), transcription factors that bind to DNA via specific sequences, in promoters of target genes. The TRs are present in cells in two isoforms, TRα and TRβ, and several lines of evidence showed that the development of ligands that bind to TRβ could lead to safer therapies for the disorders cited above. In this work, we report a synthetic route, shown in scheme 1, which allows the obtaining of two new ligands to TRs planned by structure-activity relationship (SAR) studies.

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DOI: 10.5151/chempro-15bmos-BMOS2013_2013818233325

Referências bibliográficas

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Como citar:

Castro, Guilherme V. de; Sanches, Vitor Lacerda; Donate, Paulo M.; Polikarpov, Igor; Sairre, Mirela I. de; "Synthesis of ligands for nuclear receptors of thyroid hormones", p-165-165. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_2013818233325