Structural characterization of selenium and selenium-diiodine analogues of the antithyroid drug 6-n-propyl-2-thiouracil and its alkyl derivatives

Abstract

The structures of four selenium analogues of the antithyroid drug 6-n-propyl-2-thiouracil [systematic name: 2,3-dihydro-6-n-propyl-2-thioxopyrimidin-4(1H)-one], namely 6-methyl-2-selenouracil, C(5)H(6)N(2)OSe (1), 6-ethyl-2-selenouracil, C(6)H(8)N(2)OSe (2), 6-n-propyl-2-selenouracil, C(7)H(10)N(2)OSe (3), and 6-isopropyl-2-selenouracil, C(7)H(10)N(2)OSe (4), are described, along with that of the dichloromethane monosolvate of 6-isopropyl-2-selenouracil, C(7)H(10)N(2)OSe.CH(2)Cl(2) (4.CH(2)Cl(2)). The extended structure of (1) is a two-dimensional sheet of topology 6(3) with a brick-wall architecture. The extended structures of (2) and (4) are analogous, being based on a chain of eight-membered R(8)(6)(32) hydrogen-bonded rings. In (3) and (4.CH(2)Cl(2)), R(2)(2)(8) hydrogen bonding links molecules into chains. 6-n-Propyl-2-selenouracil.I(2), C(7)H(10)N(2)OSe.I(2) (7), is a charge-transfer complex with a ;spoke' structure, the extended structure of which is based on a linear chain formed principally by intermolecular N-H...O hydrogen bonds. Re-crystallization of 6-ethyl-2-selenouracil or (7) from acetone gave crystals of the diselenides [N-(6'-ethyl-4'-pyrimidone)(6-ethyl-2-selenouracil)(2)(Se-Se)].2H(2)O (9.2H(2)O) or [N-(6'-n-propyl-4'-pyrimidone)(6-n-propyl-2-selenouracil)(2)(Se-Se)] (10), respectively: these have similar extended chain structures formed via N-H...O and C-H...O hydrogen bonds, stacked to give two-dimensional sheets. Re-crystallization of (7) from methanol/acetonitrile led via deselenation to the formation of crystals of 6-n-propyl-2-uracil (11), in which six symmetry-related molecules combine to form a six-membered R(6)(6)(24) hydrogen-bonded ring, with each pair of molecules linked by an R(2)(2)(8) motif.

Halogen Bonding with Dihalogens and Interhalogens

“…Since then, a large number of such complexes have been studied. This interest has been driven in large part by research in two areas: the unusual electric properties imparted to materials when doped with dihalogens (particularly iodine) [55], and the study of dihalogen and interhalogen complexes with potential antithyroid drugs and related derivatives, including dithiole thiones [56][57][58][59][60][61][62][63][64][65], imidazole thiones [19,[66][67][68][69][70][71][72][73] and selones [68,[74][75][76], thiazole thiones [77] and selones [78][79][80], oxazole thiones [81], and various thiourea derivatives [77,82]. Additional activity has involved the fundamental study of halogen bonding in particular classes of compounds, such as aromatic nitrogen heterocycles [31,[83][84][85][86][87][88][89][90][91][92][93][94]96], thioether...…”

Cocrystals of 6-propyl-2-thiouracil: N—H...OversusN—H...S hydrogen bonds

“…Dashed lines indicate hydrogen bonds. thiouracil (refcode PELHEU; Antoniadis et al, 2006), the molecules are hydrogen bonded into chains by R 2 2 (8) interactions involving either N-HÁ Á ÁSe or N-HÁ Á ÁO hydrogen bonds. We therefore undertook crystallization experiments with 6-propyl-2-thiouracil alone to study whether similar interactions can be observed.…”

Factors affecting drug-induced liver injury: antithyroid drugs as instances

“…The selenium-containing analogues of antithyroid drugs are synthesized, and seems to have some advantages in comparison to their sulfur containing counterparts. 48 , 49 These compounds could be newer antithyroid drug candidates. Since some investigations mentioned a potential role for "sulfur" atom in antithyroid agents to induce toxicity during metabolism, 50 substituting "sulfur" with "selenium" might reduce the risk of antithyroid drugs-induced liver injury.…”