Thiourea Compounds Research Articles

Cyanide Sensing with Organic Dyes: Studies in Solution and on Nanostructured Al2O3 Surfaces

The synthesis of two new azo phenyl thiourea compounds and their optical response to different anions is reported herein. Solution studies in methanol indicate that cyanide induces a colour change in these dyes (whereas no changes are observed in the presence of other anions, such as F(-), Cl(-), Br(-), CH(3)COO(-), H(2)PO(4) (-), HSO(4) (-)). Interestingly, in DMSO these dyes are responsive not only to cyanide, but also to fluoride, acetate and dihydrogen phosphate. Each of these anions induces a different colour change. In the second part of the paper, we report the attachment of one of these dyes onto nanostructured TiO(2) and Al(2)O(3) films. The stability of these sensitised films to pH was studied and we concluded that the sensitised Al(2)O(3) films are more robust, and hence, better than the TiO(2) for anion sensing. The dye-sensitised Al(2)O(3) films were immersed in solutions of different anions and their response studied. The films can detect cyanide down to 3 ppm in aqueous solution with relatively good selectivity over other anions.

ChemInform Abstract: Synthesis of Substituted Heterocyclic Thiourea Compounds.

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High pressure liquid chromatographic analysis ofin vivo metabolites ofN(substituted phenyl)-N′-(1,3,5-trimethyl pyrazole-4-yl)thioureas in rats

The aim of this study was to investigate the in vivo metabolism of N-(substituted phenyl)-N'-(1,3,5-trimethylpyrazole-4-yl)thioureas (substrate) as model compounds in rats via HPLC. The substrates, N-(4-fluoro/chlorophenyl)-N'-(1,3,5-trimethylpyrazole-4-yl)thioureas (T2 and T3), and their possible metabolites were synthesized and the structures of the compounds were elucidated both by spectral and elemental analysis. Substrates were dissolved in 5% gum arabic and administered 100 mg/kg intraperitoneally (i.p.) in a volume of 0.1 ml/100 g. Blood samples were withdrawn before and at 30 min, 1, 2, 4, 8, 12 and 24 h post-dose. Chromatographic separation of the substrate and its metabolites was performed using a Hichrom chromasil C18 column (150 mm x 4.6 mm i.d., 5 microm particle size). The optimal composition of the mobile phase was achieved by using different mixtures of pure methanol and water. From the biotransformation of these thiourea compounds, N-dealkylation metabolites N-(4-fluoro/chloro-phenyl)-N'-(3,5-dimethylpyrazole-4-yl)thioureas (TI and T4) were identified together with unchanged substrate (T2 and T3) in the plasma by comparing them to reference standards via HPLC UV/DAD.

Synthesis of Substituted Heterocyclic Thiourea Compounds

Heterocyclic thioureas having multiple substitutions were prepared in two steps with overall yields of 60–80%. Condensation of a substituted heterocyclic amine with thiocarbonyldiimidazole, followed by treatment with a disubstituted phenylethylamine in dimethyl formamide (DMF), yielded the desired heterocyclic thioureas as crystalline solids.

Stereochemistry as a Determinant of the Anti-Leukemic Potency of Halopyridyl and Thiazolyl Thiourea Compounds

Stereochemistry as a Determinant of the Anti-Leukemic Potency of Halopyridyl and Thiazolyl Thiourea Compounds

Thiourea Based Tweezer Anion Receptors for Selective Sensing of Fluoride Ions

AbstractThree 3,3′‐di(4‐substituted‐phenyl)‐1,1′‐isophthaloylbis(thiourea) compounds were designed as novel neutral anion receptors, and synthesized by simple steps in good yields. The single crystal structure of receptor 1 shows that a solvent molecule was captured by the host molecule through intermolecular hydrogen bonding. Moreover, it was self‐assembled as a supramolecular system for the presence of abundant inter‐ and intramolecular hydrogen bonding and π‐π interactions between phenyl groups. Their application as anion receptors has been examined by UV‐Vis and 1H NMR spectroscopy, showing that they had a higher selectivity for fluoride than other halides. The host and guest formed a 1:1 stoichiometry complex through hydrogen bonding interactions in the first step, then following a process of deprotonation in presence of an excess of F− in the solvent of DMF.

In vivo fitness and virulence of a drug-resistant herpes simplex virus 1 mutant

Two important issues regarding a virus mutant that is resistant to an antiviral drug are its ability to replicate in animal hosts (in vivo fitness) relative to other genetic variants, including wild type, and its ability to cause disease. These issues have been investigated for a herpes simplex virus 1 mutant that is resistant to thiourea compounds, which inhibit encapsidation of viral DNA. Following corneal inoculation of mice, the mutant virus replicated very similarly to its wild-type parent in the eye, trigeminal ganglion and brain. The mutant virus was as lethal to mice as its wild-type parent following this route of inoculation. Indeed, it exhibited increased virulence. Thus, unlike most drug-resistant virus mutants, this mutant retained in vivo fitness and virulence.

Synthesis of Heterocyclic Thiourea Compounds with Amino Acid Side Chain as Nonnucleoside Inhibitors of HIV‐1 Reverse Transcriptase.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of Heterocyclic Thiourea Compounds with Amino Acid Side Chain as Nonnucleoside Inhibitors of HIV‐1 Reverse Transcriptase

Heterocyclic thioureas having an amino acid ester side chain were prepared in two steps with overall yields of 65–85%. Condensation of a substituted heterocyclic amine with thiocarbonyldiimidazole, followed by treatment with an amino acid methyl ester hydrochloride in DMF, yielded the desired heterocyclic thioureas as crystalline solids. Amino acid esters such as glycine, leucine, valine, phenyl alanine, and tryptophan were used to prepare these thioureas.

Pyrrolylamidourea based anion receptors

The anion binding behaviour of a number of pyrrolylamidourea and thiourea compounds have been studied in DMSO solution. Mono-amidothioureapyrrole compounds were found to be deprotonated by basic anions such as fluoride, acetate, benzoate or dihydrogenphosphate with the structure of the deprotonated species elucidated by X-ray crystallography. 2,5-Bis-amidoureapyrroles were synthesized and found to be effective anion receptors for a range of putative anionic guests.

Synthesis of Symmetrical and Asymmetrical Phenethyl Thiourea Compounds as Nonnucleoside Inhibitors of HIV‐1 Reverse Transcriptase.

Synthesis of Symmetrical and Asymmetrical Phenethyl Thiourea Compounds as Nonnucleoside Inhibitors of HIV‐1 Reverse Transcriptase.

Synthesis of Symmetrical and Asymmetrical Phenethyl Thiourea Compounds as Nonnucleoside Inhibitors of HIV‐1 Reverse Transcriptase

Synthesis of symmetrical and asymmetrical phenethyl thioureas was accomplished in two steps with an overall yield of 75–80%. Condensation of a substituted phenethyl amine with thiocarbonyldiimidazole, followed by treatment with one more equivalent of the phenethylamine in DMF, yielded the desired symmetrical phenethyl thiourea compound as a crystalline solid. In the case of asymmetrical thiourea derivatives, different amines were selected and condensed using a similar procedure. A series of 45 thioureas was synthesized.

Structural influence on the solid state intermolecular hydrogen bonding of substituted thioureas

Several thiourea derivatives have been found to possess biological activity. In particular, phenethyl thiazolyl thiourea derivatives with a heterocyclic ring exhibit potent antiviral activity. These thiourea derivatives were also found to inhibit RT, the reverse transcriptase enzyme, by binding the non-nucleoside inhibitor site of RT. To better understand the nature of the binding of these compounds a detailed crystal structure analysis on these thiourea compounds was undertaken. Here, we report, the results of our X-ray crystal structure study of substituted thiourea compounds. Comparison of the hydrogen bonding characteristics exhibited by structurally distinct thiourea analogs was informative concerning their inter- and intramolecular hydrogen bonding. Additionally, we found that among the thioureas studied, the 2,5-dimethoxy substituted phenethyl thiourea had strong intramolecular hydrogen bonding forming a nine-member ring in the crystal lattice that was absent in the other methoxy substituted phenethyl thioureas examined. Comparison of the structures demonstrated that the presence of a heterocyclic nitrogen atom in the ring results in the formation of a stable six-member ring rather than a nine-member ring.

Synthesis of β‐Fluorophenethyl Halopyridyl Thiourea Compounds as Non‐nucleoside Inhibitors of HIV‐1 Reverse Transcriptase.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Regiospecific Synthesis of 5‐Halo‐Substituted Thiophene Pyridyl Thiourea Compounds as Non‐nucleoside Inhibitors of HIV‐1 Reverse Transcriptase.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Effect of stereochemistry on the anti-HIV activity of chiral thiourea compounds

Chiral derivatives of several substituted halopyridyl and thiazolyl PETT compounds were synthesized as non-nucleoside inhibitors of the reverse transcriptase (RT) enzyme (NNRTI) of the human immunodeficiency virus (HIV-1). Molecular modeling studies indicated that because of the asymmetric geometry of the NNRTI binding pocket, the R stereoisomers would fit the NNRTI binding pocket of the HIV-1 RT much better than the corresponding S stereoisomers, as reflected by their 10 4-fold lower K i values. The R stereoisomers of several PETT derivatives inhibited recombinant RT in vitro with lower IC 50 values than their enantiomers. The active compounds were further evaluated for their ability to inhibit HIV-1 replication in human peripheral blood mononuclear cells (PBMC). All the R isomers once again showed potent anti-HIV activity and inhibited the replication of the HIV-1 strain HTLVIIIB in peripheral blood mononuclear cells (PBMC) at nanomolar concentrations whereas their enantiomers were substantially less potent. The lead compounds in the respective groups were further tested against the NNRTI-resistant HIV strains, A17 (Y181C mutant), and A17Var (Y181C+K103N mutant) and RT MDR (V106N). The results showed that the lead compounds were several logs more potent than the standard NNRTI nevirapine. Structure–activity relationship studies also revealed a preference for the pyridyl unit with halo substitutions primarily at 5-position demonstrating the importance of regiochemistry. Our data provides experimental evidence that the stereochemistry as well as regiochemistry of NNRTI can profoundly affect their anti-HIV activity.

Synthesis of β‐Fluorophenethyl Halopyridyl Thiourea Compounds as Non‐nucleoside Inhibitors of HIV‐1 Reverse Transcriptase

Synthesis of β‐fluorophenethylamines was accomplished in three steps with an overall yield of 50%. Condensation of β‐fluorophenethylamine hydrochloride with thiocarbonylimidazole derivative derived from halopyridyl amines in dimethylformamide furnished the desired thiourea compounds as crystalline solids. Several of the β‐fluorophenethyl thiourea compounds inhibited HIV‐1 reverse transcriptase (RT) at nanomolar to low micromolar concentrations.

Regiospecific Synthesis of 5‐Halo‐substituted Thiophene Pyridyl Thiourea Compounds as Non‐nucleoside Inhibitors of HIV‐1 Reverse Transcriptase

The regiospecific synthesis of 5‐halothiophenethylamines and halo‐substituted phenylethyl thioureas was accomplished with an overall yield of 45–60%. Condensation of t‐boc protected 2‐thiophenethylamine with N‐halo succinamide in dimethylformamide furnished the desired halo‐substituted thiophenethylamines. These thiophenethyl amines were further converted into biologically active thiourea compounds using thiocarbonyldiimidazole chemistry. Several of the halo‐substituted thiophene pyridyl thiourea compounds inhibited HIV‐1 reverse transcriptase (RT) at nanomolar concentrations.

Structural influence on the anisotropic intermolecular hydrogen bonding in solid state of substituted thioureas: evidence by X-ray crystal structure

The results of an X-ray crystal structure study of 24 substituted thiourea compounds are reported. Comparison of hydrogen bonding characteristics exhibited by structurally distinct thiourea analogs is especially informative concerning the intermolecular hydrogen bonding that exists in the crystal structure of individual derivatives. In general, all the thiourea derivatives studied showed strong intramolecular hydrogen bonding within their structural framework. In addition, among the thioureas studied, with the exception of the 1-(3-aminopropyl)-imidazole substituted thioureas, all other derivatives formed intermolecular hydrogen bonding with the thiourea sulfur atom and the NH group. However, we discovered for the first time that the presence of the two nitrogen atoms in the heterocyclic ring of 1-(3-aminopropyl)-imidazolyl substituted thioureas formed the hydrogen bond between the imidazolyl N atom and NH group, consequently eliminating the CS⋯NH hydrogen bond formation as shown in the packing of the crystal lattice. The following paper describes this novel anisotropy observed in the intermolecular hydrogen bonding among these substituted thiourea derivatives and their salient lattice packing features.

Microwave-assisted traceless synthesis of thiohydantoin

An efficient, microwave-assisted method for the liquid-phase combinatorial synthesis of 3,5-disubstituted-thiohydantoin has been developed. Fmoc-protected amino acids were coupled with HO-PEG-OH and after deprotection, reacted with various isothiocyanates in microwave cavity. The PEG bound thiourea compounds underwent base mediated cyclization/cleavage step by microwave flash heating. The desired products were then liberated from the soluble matrix in good yield and purity under microwave exposure.