New Thieno-[2,3-d]pyrimidine-Based Functional Antagonist for the Receptor of Thyroid Stimulating Hormone

Abstract

Thyroid stimulating hormone (TSH) receptor antagonists are required for the treatment of TSH-dependent tumors and Graves disease. We developed the compound 5-amino-N-(tert-butyl)-4-(4-iodophenyl)-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxamide (TP48) and showed that it reduces the TSH-stimulated adenylate cyclase activity in rat thyroid membranes. Pretreatment of rats with compound TP48 (ip, 40 mg/kg) reduced the increase in the levels of total and free thyroxin in blood and the increase in the expression of thyroglobulin and D2 deiodinase genes in the thyroid gland, which are responsible for the synthesis of thyroid hormones, which were caused by intranasal administration of thyroliberin to animals (300 μg/kg). These data indicate that compound TP48 is a functional antagonist of the TSH receptor and can be used to correct the thyroid status in hyperthyroidism.

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Funding

This work was supported by the Russian Science Foundation (no. 19-75-20122). The NMR and mass spectrometric studies were carried out using the resource centers of St. Petersburg State University “Magnetic resonance research methods” and “Methods of analysis of the composition of the substance.”

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Correspondence to A. O. Shpakov.

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Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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The authors declare that they have no conflict of interest.

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Derkach, K.V., Bakhtyukov, A.A., Sorokoumov, V.N. et al. New Thieno-[2,3-d]pyrimidine-Based Functional Antagonist for the Receptor of Thyroid Stimulating Hormone. Dokl Biochem Biophys 491, 77–80 (2020). https://doi.org/10.1134/S1607672920020064

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Keywords:

  • thyroid stimulating hormone receptor, antagonist, thienopyrimidine, thyroid gland