title: Synthesis and structures of Se analogues of the antithyroid drug 6-n-propyl-2-thiouracil and its alkyl derivatives: formation of dimeric Se-Se compounds and deselenation reactions of charge-transfer adducts of diiodine.
abstract: Four selenium analogues of the antithyroid drug 6-n-propyl-2-thiouracil (PTU), of formulae RSeU, (R = methyl (Me) (1), ethyl (Et) (2), n-propyl (nPr) (3), and isopropyl (iPr) 4), have been synthesized. Reaction of 1-4 with diiodine in a 1:1 molar ratio in dichloromethane results in the formation of [(RSeU)I(2)] (R = methyl (5), ethyl (6), n-propyl (7) and isopropyl (8)). All compounds have been characterized by elemental analysis, FT-Raman, FT-IR, UV/Vis, (1)H-, (13)C-, (77)Se-1D and -2D NMR spectroscopy, and ESI-MS spectrometric techniques. Recrystallization of 4 from dichloromethane afforded (4CH(2)Cl(2)). Crystals of [(nPrSeU)I(2)] (7), a charge-transfer complex, were obtained from chloroform solutions, while crystallization of 6 and 7 from acetone afforded the diselenides [N-(6-Et-4-pyrimidone)(6-EtSeU)(2)] (92 H(2)O) and [N-(6-nPr-4-pyrimidone)(6-nPrSeU)(2)] (10) as oxidation products. Recrystallization of 7 from methanol/acetonitrile solutions led to deselenation with the formation of 6-n-propyl-2-uracil (nPrU) (11). [(nPrSeU)I(2)] (7) was found to be a charge-transfer complex with a Se--I bond. These results are discussed in relation to the mechanism of action of antithyroid drugs.
authors.affiliation: Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Constantinos D
authors.initials: CD
authors.lastname: Antoniadis
authors.forename: Sotiris K
authors.initials: SK
authors.lastname: Hadjikakou
authors.forename: Nick
authors.initials: N
authors.lastname: Hadjiliadis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papakyriakou
authors.forename: Martin
authors.initials: M
authors.lastname: Baril
authors.forename: Ian S
authors.initials: IS
authors.lastname: Butler
mesh_terms: D013956:Antithyroid Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D007455:Iodine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011441:Propylthiouracil / Q000031:analogs & derivatives* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
chemical_list: D013956:Antithyroid Agents; D016566:Organoselenium Compounds; D011441:Propylthiouracil; D007455:Iodine