Pyrimidine Thione Research Articles

Synthesis, characterization and evaluation of thiopyrimidine derivatives as possible antimicrobial agents

A series of new thiopyrimidine derivatives have been synthesized via the reaction of Chalcones 3a-c with thiourea to give the corresponding pyrimidine thiones 4a-c. S-alkylation of pyrimidine thiones have resulted in novel 4,6-diaryl-2-alkyl thiopyrimidine 5a-i derivatives. Molecular properties like number of hydrogen bond acceptors, number of hydrogen bond donors, volume, polar surface area, molar refractivity, number of rotatable bonds and drug likeness for synthesized compounds have been predicted by using different softwares such as Molinspiration, Molsoft and Chemsketch. The newly synthesized 4,6-diaryl-2-alkyl thiopyrimidine derivatives 5a-i have been evaluated for their possible anti-microbial activity. Compounds 5b, 5d and 5e have revealed significant activity against E. coli, P. aerugenosa (Gram +ve) and B. subtilis, S. aureus (Gram −ve) species while compounds 5a, 5c, 5f-i are moderately active as compared to the standard drug Ciprofloxacin. Compounds 5c and 5g show potent anti-fungal activity against Penicillium species amongst the series in comparison to the standard Fluconazole.

Utility of Pyrimidine Thione Derivatives in the Synthesis of Biologically Active Heterocyclic Compounds

A new series of thieno[2,3-b]pyridine-2-carbohydrazide, 2,3 dihydropyrido[3′,2′:4,5]-thieno[3,2-d]pyrimidin-4(1H)-one, thieno[2,3-b]pyridin-2 yl)(3,5-substituted-1H-pyrazol-1-yl)methanone, tetrazolopyrimidine, and triazolopyrimdine derivatives have been synthesized. Molecular docking studies were performed on the most active compounds against the aspartic protease from Candida albicnas (1ZAP) and gram-negative (Salmonella typhimurium) binding protein (3ZQB) revealed the potential binding mode of the ligands to the site of the appropriate targets. To determine the direction of the reaction, compounds (19a) and (20a) were subjected to a computational study. Computational investigations are in complete agreement with experimental findings. Moreover, the selected newly synthesized products were evaluated for their antimicrobial activity.

Thione Derivatives as Medicinally Important Compounds

AbstractLike nitrogen‐containing heterocycles, sulfur‐containing heterocyclic compounds also have a lot of significant applications. These sulfur heterocycles are mainly used as a core for the synthesis of different heterocyclic compounds with various biological applications. It also occupies a huge part of natural products. In this review, we focus on the thiones‐the analogous of ketones. Syntheses of thiones as well as their applications as biologically active compounds are discussed in great detail. We have considered seven different classes of thiones such as Benzimidazole thiones, Triazole thiones, Pyrimidine thiones, Thiadiazine thiones, Thiazoline thiones, Thiazolidine thiones, and Quinazoline thiones.

Synthesis, Structural Studies, and Anticancer Properties of [CuBr(PPh3)2(4,6-Dimethyl-2-Thiopyrimidine-κS

CuBr(PPh3)2(4,6-dimethylpyrimidine-2-thione) (Cu-L) was synthesized by stirring CuBr(PPh3)3 and 4,6-dimethylpyrimidine-2-thione in dichloromethane. The crystal structure of Cu-L was obtained, and indicated that the complex adopts a distorted tetrahedral structure with several intramolecular hydrogen bonds. Moreover, a centrosymmetric dimer is formed by the intermolecular hydrogen bonding of the bromine acceptor created by symmetry operation 1−x, 1−y, 1−z to the methyl group (D3 = C42) of the pyrimidine–thione ligand. HSA-binding of Cu-L and its ligand were evaluated, revealing that Cu-L binds to HSA differently than its ligand. The HSA-bindings were modeled by molecular docking, which suggested that Cu-L binds to the II A domain while L binds between the I B and II A domains. Anticancer activities toward OVCAR-3 and HeLa cell lines were tested and indicated the significance of the copper center in enhancing the cytotoxic effect; negligible toxicities for L and Cu-L were observed towards a non-cancer cell line. The current study highlights the potential of copper(I)-phosphine complexes containing thione ligands as therapeutic agents.

Design, Synthesis and In-vivo Anti-inflammatory Activity of New Celecoxib Analogues as NSAID.

A new series of Celecoxib analogues were easily synthesized via reactions of 4-(2-(1-chloro-2-oxopropylidene)hydrazinyl)benzene sulfonamide (1) with active methylene compounds and dialkyl malonate. In addition, compound 1 was reacted also with thiourea derivatives and thiosemicarbazone derivatives to afford thiazole derivatives 9 and 11, respectively. Furthermore, triazolo pyrimidine derivatives 13 were prepared via reaction of compound 1 with pyrimidine thione derivatives. The structures of the new synthesized compounds were assigned by elemental analysis and spectroscopic data. The new analogues were screened for their in vivo anti-inflammatory activity using carrageenan-induced paw edema method. They showed moderate to good in vivo anti-inflammatory effects. Compounds 1, 6 and 11b were the most active compounds that reduced the paw edema induced by carrageenan by 12.25 %, 12.96 % and 12.97% respectively, as compared to the Indomethacin that inhibited the oedema volume by 7.47 %.

Utility of 2‐Acetyl Benzofuran for the Synthesis of New Heterocycles as Potential Anticancer Agents

A novel series of benzofuran derivatives containing thiazole, thiadiazine, and pyridotriazolopyrimidine were synthesized starting from 1‐(benzofuran‐2‐yl)‐3‐(1H–indol‐3‐yl)prop‐2‐en‐1‐one. Also, triazolopyrimidine derivatives were prepared from the reaction of 2‐acetylbenzofuran and pyrazole‐4‐carbaldehyde with 2‐thiobarbutyric acid and reaction of the product with hydrazonoyl halides. The structures of the newly synthesized compounds were elucidated on the basis of elemental analyses, spectral data, and alternative synthetic routes whenever possible. Anticancer activity against 60 different human tumor cell lines representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney was validated by the U.S. National Cancer Institute using a two‐stage process. The results revealed that pyrazoline‐1‐thiocarbohydrazide 4b, triazolopyrimidine 20d, and pyrimidine thione 25 have promising antitumor activity against most cell lines.

Antimicrobial Activity of Novel Tetra‐ and Penta‐azaheterocyclic Ring Systems

A novel series of substituted [1,2,4]triazolo[4′,3′:1,2]pyrimido[4,5‐c]benzo[f]isoquinolin‐14(10H)‐one was synthesized from the reaction of hydrazonoyl chlorides with pyrimidine thione derivative or via oxidative cyclization of 3‐(2‐substituted‐benzylidene‐hydrazinyl)‐7,8‐dihydrobenzo[f]pyrimido[4,5‐c]isoquinolin‐1(2H)‐one. Also, some polyhetero‐cyclic ring systems were prepared through the reaction of 2‐dimethylaminomethylene‐3,4‐dihydro‐2H‐naphthalen‐1‐one and heterocyclic amines. The biological activity of some new products was evaluated, and the results obtained revealed that compounds 10e, 13a, and 18 showed excellent activities against the most bacteria and fungi species used.

ChemInform Abstract: A New and Facile Synthesis of Novel Pyrazolothienopyrimidines and Imidazopyrazolothienopyrimidines.

4-Amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carboxamide (5), which was synthesized by an innovative method, was used as a versatile precursor for synthesizing pyrazolothienopyrimidines and imidazopyrazolothienopyrimidines compounds. Reaction of amino thienopyrazole carboxamide 5 with triethyl orthoformate afforded thienopyrazolopyrimidine 6. Chlorination of the latter compound, using phosphorus oxychloride afforded the chloro pyrazolothienopyrimidine 7, which underwent nucleophilic substitution reactions with various primary and secondary amines to give the alkyl (aryl) amino pyrimidine compounds 8a–d. On the other hand, the reaction of chloropyrimidine 7 with thiourea afforded the pyrimidine thione compound 9, which was alkylated with α-halogentaed compounds to afford the S-alkylated derivatives 10a–c. Also, chloroacetylation of the amino carboxamide 5 using chloroacetyl chloride yielded the chloromethyl pyrazolothienopyrimidine 12, which underwent nucleophilic substitu- tion reactions with various primary and secondary amines to afford the alkyl (aryl) aminomethyl compounds 13a–f. The latter Compounds underwent Mannich reaction to give imidazopyrimidothieno- pyrazoles 14a–c. The newly synthesized compounds and their derivatives were fully characterized by elemental and spectral analysis.

Kinetics Study of the Formation of Pyrmidine Thione from the Reaction of 2,6-Dibenzylidinecyclohexanone and its Derivatives with Thiourea

Kinetics of the addition of thiourea to 2,6-dibenzylidenecyclohexanone and its derivatives have been studied. The reaction is found as a pseudo-first order process which includes a nucleophilic attack by thiourea at the carbonyl group of the ketone system to produce the heterocyclic pyrimidine thione thiopyrimidine (Claisen route mechanism). The effect of the substituents at the para position of the 2,6-dibenzylidenecyclohexanone and its derivatives on the rate of reaction, at different temperatures, is studied. Arrhenius parameters, entropies, enthalpies and free energies of activations are estimated. A suitable mechanism, which is correspondent with the results and with Claisen routes mechanism, is suggested for this reaction.

Synthesis of N-alkyl (aril)-tetra pyrimidine thiones and investigation of their human carbonic anhydrase I and II inhibitory effects

Tetrahydropyrimidine thiones, which are cyclic thiocarbamides derivatives, were synthesised from thiourea, β-diketones and substituted benzaldehydes. A tautomeric form of these derivatives incorporates the thiol functionality, which is known to interact with metal ions from metalloenzymes active sites, such as the carbonic anhydrases (CAs, EC 4.2.1.1) among others. This is a superfamily of widespread enzymes, which catalyses a crucial biochemical reaction, the reversible hydration of carbon dioxide to bicarbonate and protons (H+). The newly synthesised N-alkyl (aril)-tetrahydropyrimidine thiones were tested for inhibition of the cytosolic human isoforms I and II (hCA I and II). Both isoforms were effectively inhibited by the newly synthesised thiones. Ki values were in the range of 218.5 ± 23.9–261.0 ± 41.5 pM for hCA I, and of 181.8 ± 41.9–273.6 ± 41.4 pM for hCA II, respectively. This under-investigated class of derivatives may bring interesting insights in the field of non-sulphonamide CA inhibitors.

A New and Facile Synthesis of Novel Pyrazolothienopyrimidines and Imidazopyrazolothienopyrimidines

Abstract4‐Amino‐3‐methyl‐1‐phenyl‐1H‐thieno[2,3‐c]pyrazole‐5‐carboxamide (5), which was synthesized by an innovative method, was used as a versatile precursor for synthesizing pyrazolothienopyrimidines and imidazopyrazolothienopyrimidines compounds. Reaction of amino thienopyrazole carboxamide 5 with triethyl orthoformate afforded thienopyrazolopyrimidine 6. Chlorination of the latter compound, using phosphorus oxychloride afforded the chloro pyrazolothienopyrimidine 7, which underwent nucleophilic substitution reactions with various primary and secondary amines to give the alkyl (aryl) amino pyrimidine compounds 8a–d. On the other hand, the reaction of chloropyrimidine 7 with thiourea afforded the pyrimidine thione compound 9, which was alkylated with α‐halogentaed compounds to afford the S‐alkylated derivatives 10a–c. Also, chloroacetylation of the amino carboxamide 5 using chloroacetyl chloride yielded the chloromethyl pyrazolothienopyrimidine 12, which underwent nucleophilic substitu‐ tion reactions with various primary and secondary amines to afford the alkyl (aryl) aminomethyl compounds 13a–f. The latter Compounds underwent Mannich reaction to give imidazopyrimidothieno‐ pyrazoles 14a–c. The newly synthesized compounds and their derivatives were fully characterized by elemental and spectral analysis.

Study of Coordination Characteristics of some Metal Complexes of 2-Thiouracil by Infrared Spectroscopy

The infrared spectra of 2-Thiouracil (Thu) have been recorded in the region 4000-400 cm-1. The assignments of fundamental frequencies have been proposed on the basis of assignments in related molecules. Correlation of vibrational assignments with those of related molecules have been pointed out. The metal ion interactions of Thu with Cd (II), Hg (II), Cu (II), and Zn (II) bromides have been investigated by infrared spectroscopy. The results are consistent with the bonding of ligands through sulphur in all the complexes. The vibrational frequencies of metal complexes of 2-Thiouracil are correlated with the spectral data of other structurally related pyrimidine thione complexes.

Study of Coordination Characteristics of some Metal Complexes of 2-Thiouracil by Infrared Spectroscopy

The infrared spectra of 2-Thiouracil (Thu) have been recorded in the region 4000-400 cm-1. The assignments of fundamental frequencies have been proposed on the basis of assignments in related molecules. Correlation of vibrational assignments with those of related molecules have been pointed out. The metal ion interactions of Thu with Cd (II), Hg (II), Cu (II), and Zn (II) bromides have been investigated by infrared spectroscopy. The results are consistent with the bonding of ligands through sulphur in all the complexes. The vibrational frequencies of metal complexes of 2-Thiouracil are correlated with the spectral data of other structurally related pyrimidine thione complexes.

Synthesis and studies of pyrazolo[3,4-b]piperidin-4-one derivatives

A series of isolated/fused of pyrazole, isoxazolo, pyrimidine, pyrimidine thione, spiro thiazolodine and spiro β-lactam derivatives incorporating to 4-acetyl-5-amino-3-methyl-1-phenyl-2-pyrazoline have been synthesized by different methods of chemical reactions. The structure assignments of these compounds, based on chemical and spectroscopic evidence were deduced from their IR, 1 H NMR, elemental analysis and mass spectrometry.

Synthesis and studies of pyrazolo[3,4-b]pyridin-4-one derivatives

A series of isolated/fused of pyrazole, isoxazolo, pyrimidine, pyrimidine thione, spiro thiazolodine and spiro β-lactam derivatives incorporating to 4-acetyl-5-imino-3-methyl-1-phenyl-2-pyrazoline have been synthesized by different methods. The structure of chemical reactions based on chemical and spectroscopic evidence. The detailed synthesis and spectroscopic data were reported.

ChemInform Abstract: A Facile One Pot Conversion of Chalcones to Pyrimidine Thione Derivatives. Ring Opening Reactions of Oxiranes Derived from Chalcones.

Arylidene 2,5-dimethylacetophenones (1) reacted with thiourea and hydrogen peroxide to give pyrimidinethione (2) and oxirane derivatives (7), respectively. The behaviour of pyrimidinethione (2) towards hydrazine, acetylhydrazines, secondary amines under Michael reaction conditions, and phenylisocyanate has been investigated. The reaction of oxirane derivative (7) with aqueous sodium hydroxide, glacial acetic acid and p-xylene under Friedel Crafts reaction conditions is also described

Antiviral and Antischistosomal Evaluation of Newly Synthesized Thioglycosides and their Acyclic Analogues

The pyrimidine thione derivatives 2a-d were prepared by the reaction of thiourea, ethyl cyanoacetate and several aromatic aldehydes. The acyclic thioglycosides 4a-7d were prepared by the reaction of the synthesized pyrimidine thiones 2a-d with different alkyl halides, whereas the reaction of 2a-d with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide afforded the cyclic thioglycosides 8a-d whose deprotection afforded 9a-d. The obtained compounds were tested for their antischistosomal and antiviral activity against hepatitis B virus (HBV). Compounds 5a, 5d, 7a showed high activity against HBV using the MTT assay; moreover compounds 5c, 6d, 7a, 9a, 9c exhibited high activity as antischistosomal agents.

Novel Fluoro Substituted Benzo[b]pyran with anti‐Lung Cancer Activity.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and Reactions of New Substituted Pyrimidine Thione Derivatives as Antimicrobial Agents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chemically modified carbon paste electrode for determination of copper(II) by potentiometric method

The utility of carbon paste electrode modified with DTPT (3,4-dihydro-4,4,6-trimethyl-2(1H)-pyrimidine thione) for the potentiometric determination of Cu(II) in aqueous medium is demonstrated. The electrode exhibits linear response to Cu(II) over a wide concentration range (9.77×10 −7–7.6×10 −2) with Nernstian slope of 30±2 mV per decade. It has a response time of about 45 s and can be used for a period of two months with good reproducibility. The detection limit of this electrode was 7.0×10 −7 M. The proposed electrode shows a very good selectivity for Cu(II) over a wide variety of metal ions. This chemically modified carbon paste electrode was successfully used for the determination of Cu(II) in electronics waste sample solution.