Thyroid disorders, dementia and Down syndrome
Vee P. Prasher in Down Syndrome and Alzheimer’s Disease, 2018
This is treated by one of three modalities, namely antithyroid medications, subtotal or total thyroidectomy, or radioactive iodine ablation.135,137,184 In many cases these treatments can render the patient euthyroid, but they all have potential adverse effects. Drug treatment may not eliminate recurrences. Pregnant women with hyperthyroidism should be treated with drugs or surgery and not with radioactive iodine, as the latter may have adverse effects on the neonate, such as prematurity, intrauterine growth retardation and fetal or neonatal thyrotoxicosis. Antithyroid medications include the thionamide drugs thiamazole and propylthiouracil. Rare side-effects include rash, itching, fever, liver inflammation or white-blood-cell deficiency. When these drugs are discontinued the problem usually recurs. Radioactive iodine treatment for hyperthyroidism can be administered by mouth without the need for hospitalisation. The majority of patients are cured, but they may end up hypothyroid. Surgical removal of all or part of the thyroid gland as warranted is a permanent cure. This is highly suitable for removing nodules, but not for treating Graves’ disease, which affects the whole thyroid. With removal of much or all of the gland comes the need for permanent hypothyroid medication. Surgery also carries the risk of injury to the recurrent laryngeal nerve (the nerve to the voice box).
Hyperthyroidism
Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner in Endocrine Surgery, 2017
The major agents for treating thyrotoxicosis are drugs of the thionamide class, most commonly methimazole (Tapazole) and less commonly propylthiouracil (PTU). These agents inhibit the oxidation and organic binding of thyroid iodide. In addition, large doses of PTU (400 mg) impair the conversion of T4 to T3 by deiodinase type I in the thyroid and peripheral tissues [8]. The half-life of methimazole is about 6 hours, whereas that of PTU is about 1½ hours. Hence, a single daily dose of methimazole may be sufficient. Thionamide drugs may also directly influence the immune response within the thyroid gland of patients with Graves’ disease, where the drugs are concentrated [9]. The clinical importance of this immunosuppression and coincidental induction of apoptosis is unclear.
Autoimmune endocrine disease
Philip E. Harris, Pierre-Marc G. Bouloux in Endocrinology in Clinical Practice, 2014
Thioamides have been used since the early 1940s. Propylthiouracil (PTU) and methimazole (MMI) were previously preferred in Europe, Asia, and North America. However, increasing focus on PTU-related adverse effects, especially in childhood GD, has resulted in the recommendation of replacing PTU as a first-line drug, with the exception of the first trimester of pregnancy.18–20 Carbimazole (CBZ), a precursor of MMI, is preferred in the United Kingdom. The major action of ATDs is to inhibit thyroid hormone synthesis by interfering with thyroid peroxidase–mediated iodination of tyrosine residues in thyroglobulin. PTU inhibits the type 1 deiodinase enzyme that converts T4 to T3.
Safety of antithyroid drugs in pregnancy: update and therapy implications
Published in Expert Opinion on Drug Safety, 2020
Thanuya Francis, Niroshan Francis, John H. Lazarus, Onyebuchi E. Okosieme
The thionamide antithyroid drugs are 5–6 ringed sulfur containing thiourea derivatives that inhibit thyroid hormone synthesis by preventing thyroid peroxidize (TPO) catalyzed iodination and coupling of thyroglobulin-linked tyrosine residues [22,23]. The thionamides also have immunosuppressive effects which over time leads to a reduction in TRAb levels but it is unclear whether these immunosuppressive effects are as a result of direct actions on humoral and cellular mechanisms or an indirect effect of hyperthyroidism control [22]. In addition, PTU in large doses blocks peripheral thyroxine (T4) to triiodothyronine (T3) conversion through inhibition of the type 1 deiodinase [22,23]. Lastly, the thionamides may exhibit antioxidant properties but it is also unclear if this action occurs through direct effects or through control of hyperthyroidism.
Synthesis, antiasthmatic, and insecticidal/antifungal activities of allosamidins
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Gangliang Huang, Hualiang Huang
The synthesis of disaccharide and trisaccharide thiazolines 24 and 25 began with octaacetylchitobiose 26 and undecaacetylchitotriose 27 in turn (Scheme 6)56. The α-configuration of acetoxy groups of compounds 26 and 27 was reversed to give the corresponding β-anomers, the anomeric chlorides were obtained by the initial treatment with HCl and AcOH, and then treated with AgOAc/AcOH. After treatment with Lawesson reagent, thiazolines 28 and 29 were obtained by affecting both the conversion of amides to thioamides and the intramolecular substitution of adjacent thioamide sulfur atom to the anomeric β-acetoxy group. The partial deacetylation of per-O-acetylated thiazolines 28 and 29 gave two additional chitinase inhibitors, namely the chitobiose thiazoline thioamide 30 in a yield of 89% and chitotriose thiazoline dithioamide 31 in a yield of 80%. To synthesize target compounds 24 and 25, thioamides 28 and 29 were converted to diacetylimides 32 and 33 (81% and 60% yields in turn) with silver acetate/dichloromethane without destroying the thiazoline part. Finally, chitobiose thiazoline 24 (69% yield) and chitotriose thiazoline 25 (78% yield) were obtained by O-deacylation and mono-N-deacylation of imides 32 and 33 with sodium methanol/methanol.
Synthesis, antitumor activity, and molecular docking study of 2-cyclopentyloxyanisole derivatives: mechanistic study of enzyme inhibition
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Walaa M. El-Husseiny, Magda A.-A. El-Sayed, Adel S. El-Azab, Nawaf A. AlSaif, Mohammed M. Alanazi, Alaa A.-M. Abdel-Aziz
The synthesis of imidazole via multicomponent reactions (MCRs) was achieved through the cyclocondensation of 1,2-diketone, an aldehyde, and ammonium acetate using a catalytic amount of ceric ammonium sulphate (CAS) or molecular iodine47,48 (Scheme 2). Thus, a one-pot synthesis achieved phenanthroimidazole derivatives 7a–e in good yield via the cyclocondensation of 9,10-phenanthraquinone, 3-cyclopentyloxy-4-methoxybenzaldehyde (2), and ammonium acetate in the presence of 5% mole of iodine or CAS. Furthermore, acridinedione 8 was prepared by a one-pot, three-component cyclocondensation reaction of 3-cyclopentyloxy-4-methoxybenzaldehyde (2), 1,3-dicarbonyl compound (dimedone), and ammonium acetate in the presence of a catalytic amount of 5% CAS using polyethylene glycol (PEG) as a solvent49. Thioamides 9a–c, 10, and 11 were synthesised50 by the reaction of elemental sulphur (S8), 3-cyclopentyloxy-4-methoxybenzaldehyde (2), and secondary amines, such as piperidine, morpholine, N-Boc-piperazine, and dimethylamine, or primary amines, such as 4-fluoroaniline in dimethylformamide (DMF), under heating condition.
Related Knowledge Centers
- Functional Group
- Organyl Group
- Hydrogen
- Amide
- Thioacetamide
- Sulfide
- Medication
- Hyperthyroidism
- Phosphorus Pentasulfide
- Lawesson'S Reagent