Drug Therapy in Laryngology and Head and Neck Surgery
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
Antithyroid drugs are used for hyperthyroidism either preoperatively or for long-term management. Carbimazole (Neo-Mercazole) is the most commonly used in the UK; propyluracil is used in patients sensitive to carbimazole. Both are thionamides containing a thiocarbamide group (S = C – N) that is essential for their activity. Carbimazole is rapidly converted to methimazole in vivo. Methimazole is available in the USA. Thioamides prevent the synthesis of thyroid hormones by competitive inhibition of I– to I2 by peroxidase and also block the coupling of the iodotyrosine, especially in forming diiodothyronine. More controversial is the possibility that the thionamides have immunosuppressive properties. These drugs are administered orally and accumulate within the thyroid gland. Their delayed onset of action of 3 to 4 weeks results from the need of preformed hormones to be depleted first.
Third Histamine Receptor: From Discovery to Clinics, Long-Lasting Love Story at INSERM and Bioprojet
Divya Vohora in The Third Histamine Receptor, 2008
Thioperamide rather rapidly showed its hepatotoxicity in rats, a deceiving observation that we could have, probably, anticipated from the presence of a thioamide group in its structure that had been introduced for synthesis commodity. On its side, R-α-methylhistamine, which displays acceptable pharmacokinetics in rodents, revealed its unacceptably short half-life in medical students, that is, healthy human volunteers. Hence these two failures led us to interrupt the development of both compounds, which, nevertheless, continued their long and successful lives as prototypic pharmacological tools (more than 600 and nearly 300 Pubmed citations for thioperamide and R-α-methylhistamine, respectively, during their first 20 years of existence).
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.
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.
Exploring structure-activity relationship of S-substituted 2-mercaptoquinazolin-4(3H)-one including 4-ethylbenzenesulfonamides as human carbonic anhydrase inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Adel S. El-Azab, Alaa A.-M. Abdel-Aziz, Hany E. A. Ahmed, Sivia Bua, Alessio Nocentini, Nawaf A. AlSaif, Ahmad J. Obaidullah, Mohamed M. Hefnawy, Claudiu T. Supuran
4-(2-(4-Oxo-2-thioxo-1,4-dihydroquinazolin-3(2H)-yl)ethyl)benzenesulfonamide (1) was obtained through the reaction between anthranilic acid, 4-(2-isothiocyanatoethyl)benzenesulfonamide and triethylamine in ethanol40,54 (Scheme 1). Its yield was 93%. Stirring of compound 1 with potassium carbonate in acetone and different alkyl-halides or aralkyl-halides produced the corresponding 4-(2-(2-(substituted-thio)-4-oxoquinazolin-3(4H)-yl)ethyl)benzenesulfonamides 2–13 with 90–95% yield. Various spectral analyses were performed to confirm the structures of compounds 2–13. The formation of target compounds was assessed by the disappearance of thioamide proton (NH–C = S) at 13.03 ppm in 1H NMR and thione moiety (NH–C = S) at 175.29 ppm in the 13C NMR spectra, together with presence of the new thio-substituted moieties (S–R), that were confirmed by 1H NMR and 13C NMR spectra.
Related Knowledge Centers
- Functional Group
- Organyl Group
- Hydrogen
- Amide
- Thioacetamide
- Sulfide
- Medication
- Hyperthyroidism
- Phosphorus Pentasulfide
- Lawesson'S Reagent