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A facile and efficient protocol for one-pot three-component synthesis of a series of novel 4-substituted-2-thioxo-3,4-dihydro-1H-pyrido[1,2-a]pyrimido[4,5-d]pyrimidin-5(2H)-one derivatives has been developed. Compounds were synthesized by the reaction of 2H-pyrido[1,2-a]pyrimidine-2,4(3H)-dione, various aromatic aldehydes, and thiourea using Iodine as catalyst in acidic medium. The synthesized compounds obtained in good to excellent yields (52–83%) with improved reaction time and chloro substituent at four-position yielded the product in excellent quantity (83%). The synthesized compounds have been characterized by 1H, and 13C NMR, IR, and mass spectral analysis, and screened for their in vitro antibacterial activity against Bacillus subtilis, Salmonella typhemurium, Escherichia. coli, and Staphylococcus aureus using disk diffusion method. Biological screening revealed that the newly synthesized compounds exhibit interesting activities against several bacterial strains. Among all the synthesized compounds, the in vitro antibacterial activity displayed by compound 6j was highest against S. typhemurium with ZOI 23.5. mm (MIC = 3.125 µg/mL). Docking studies further supported the findings, and provided for the basis of linkages in terms of conventional hydrogen bonds, and pi- bonding patterns. In nutshell, the present study thus paved the way for developing lead compounds which could be potentially used as an efficient antibacterial drug in humans after appropriate animal, and clinical trials. [ABSTRACT FROM AUTHOR]

Pyridopyrimidine are heterocyclic molecules enclosing fused pyridine and pyrimidine rings. Owing to its fascinating core structure and pharmacological applications a series of 7-([1,1′-biphenyl]-4-yl)-5-arylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones were synthesized and characterized using IR, 1H, 13C NMR and Mass spectral techniques. The antibacterial, antioxidant and anticancer activities were investigated for the synthesized compound 5a-5f. Compounds with electron-donating groups showed excellent free radical scavenging activity. Halogen-substituted compounds showed more potent antimicrobial and anticancer activity than other derivatives in comparison with their respective standards. Based on the IC50 value obtained from anticancer activity, 5c was further analyzed for apoptosis by AO/EB staining method. The findings suggested early apoptosis in the MCF-7 cell line. Molecular Docking studies of the synthesized compounds were performed with Kinase 1 inhibitors (PDB id: 2YEX), 5c exposed good docking results with minimum binding energy. Further, these compounds were acknowledged as orally active drug candidates from in-silico ADMET studies. Computational analysis supports biological findings indicating compound 5c as a promising anticancer agent against the human breast cancer MCF-7 cell line. [ABSTRACT FROM AUTHOR]

The current research is directed to construct a novel category of linear annulated chromeno[3',2':5,6]pyrido[2,3-d][1,3]thiazolo[3,2-a]pyrimidines. The chemical reactivity of the recently synthesized aldehyde 1 was examined toward a diversity cyclic methylene ketones, cyclic enamines and cyclic enols. Friedländer condensation of aldehyde 1 with 1,3-cyclohexanediones gave the multi-linear chromenopyrido- pyrimidothiazoloquinolines 2 and 3. Also, treating aldehyde 1 with some pyrazolones furnished annulated chromenopyridopyrazolopyridothiazolopyrimidines 4-6. Further, 1,3-thiazolidine-2,4-dione and barbituric acid condensed with aldehyde 1 giving chromenopyridothiazolopyridothiazolopyrimidine 7 and chromenopyridopyrimido-thiazolopyridopyrimidine 8, respectively. Moreover, reacting aldehyde 1 with cyclic enamines (6-amino-2-thiouracil and 6-amino-1,3-dimethyluracil) and cyclic enols (4-hydroxycoumarin and 1-ethyl-4-hydroxyquinolin-2(1H)-one) furnished polyfused heterocycles 9-12, respectively. During in vitro investigation of the antimicrobial efficiency, the synthesized compounds showed considerable activity against yeast and fungal strains, as well as moderate to high activity against Gram-positive and Gram-negative bacteria. Polyfused compounds 4-6 showed significant efficiency against all types of tested microorganisms. [ABSTRACT FROM AUTHOR]

The starting substrate 5-chloro-4,9-dimethoxy-7-oxo-7H-furo[3,2-g]chromene-6-carbonitrile (2) was efficiently synthesized from chlorination of the corresponding hydroxy derivative. The presence of adjacent cyano and chloro functions was employed for construction a variety of five, six and seven membered rings annulated furo[3,2-g]chromenes. Treating precursor 2 with hydrazine, phenylhydrazine and hydroxylamine yielded furo[3,2:6,7]chromeno[4,3-c]pyrazoles 3, 4 and furo[3,2:6,7] chromeno[3,4-d]isoxazole 5, respectively. Also, reaction of compound 2 with a diversity of 1,3-N,N-binucleophiles such as guanidine, cyanoguanidine, thiourea, acetamidine and benzamidine produced annulated furo[3,2:6,7]chromeno[4,3-d]pyrimidines 6–10, respectively. Further, treatment of compound 2 with a variety of 1,4-binucleophiles namely ethylenediamine, o-phenylenediamine and 2-aminophenol yielded furo[3,2:6,7]chromeno[4,3-e][1,4]diazepine 11, furo[3,2:6,7]chromeno[4,3-b][1,5]benzodiazepine 12 and furo[3,2:6,7]chromeno[4,3-b][1,5]benzoxazepine 13, respectively. Some of the synthesized compounds seemed good antimicrobial activity especially compounds 3, 6 and 8. Using analytical and spectral results, the structures of the prepared compounds were established. [ABSTRACT FROM AUTHOR]

A new bunch of substituted aryl amino derivatives structurally modified pyrido[3,2-d]pyrimidines (10a–j) have been synthesized and evaluated for anticancer effects against PC3 (human prostate), A549 (human lung), MCF-7 (human breast) and Colo-205 (human colon) cancer cell lines by utilizing of MTT procedure. Most of the synthesized compounds were showed anticancer activity good to moderate activities with IC50 values range from 0.013 ± 0.0058 µM to 8.22 ± 5.87 µM, whereas, standard 9 etoposide used as standard drug) showed IC50 values from 0.14 ± 0.017 µM to 3.08 ± 0.135 µM, respectively. Among the synthesized compounds, five compounds 10a, 10b, 10c, 10d and 10e demonstrated more potent activity on all cell lines. Mainly, compound 10e displayed higher anticancer activity. [ABSTRACT FROM AUTHOR]

A novel and highly efficient synthetic route to [1,3,4]thiadiazolo[3,2-a]pyrimidine derivatives from 5-amino-1,3,4-thiadiazole-2-thiol, various aromatic aldehydes, and Meldrum's acid in the presence of acetic acid in dry ethanol has been reported. We designed the three-component reaction with the incorporation of Knoevenagel condensation followed by an intermolecular nucleophilic addition reaction in one pot under mild conditions. The structural diversities of these synthesized compounds have been confirmed spectroscopically, by IR, 1H-, and 13C NMR, and elemental analysis, which agree with the proposed structures. [ABSTRACT FROM AUTHOR]

A facile, environmentally benign and proficient route has been developed for the diverse synthesis of pyrrolo[2,3-d]pyrimidine derivatives followed by heterocyclization starting from Amino uracil, arylgyoxal and malononitrile/thiols. Readily available thiamin hydrochloride organocatalyst was used as a green promoting medium. As well as the reaction progress was taken place under aqueous media. This procedure also offers a base and metal free approach which endowed high yields with better functional group tolerating ability and mild reaction conditions. Further, methodology had a widescope with recyclability and reuse of thiamin hydrochloride. DFT/TD-DFT calculations with B3LYP/6-311G++ level of theory were used to study the optimized geometry and HOMO-LUMO energy of the synthesized compounds (4b and 6i). [ABSTRACT FROM AUTHOR]

In here, a series of pyrimidin-(1(2H)-yl)acetamide and pyrimidin-(1(2H)-yl)isophthalimide derivatives were synthesised according to literature. The cytotoxic activity properties of these molecules were screened against human cancer cell lines as in vitro. The results demonstrated that these molecules had moderate effects on cancer cell lines for 48 h. The binding potential of the relatively active compound, ZF1, towards CDK1 (cyclin-dependent kinase 1) was investigated through molecular docking. The stability of the enzyme-ZF1 complex procured from the molecular docking was assessed through molecular dynamics (MD) simulation. Then, the electrochemical properties of the synthesised compounds were computed through density functional theory (DFT) studies. Computational pharmacokinetic analysis was also performed. The computational studies revealed that ZF1 could bind to CDK1 but its binding potential was less than the standard drug. The MD simulation exhibited that the compound could be stable inside the binding region during the simulation period. ZP3 is predicted to have the highest chemical stability among the synthesised compounds. Furthermore, the computational pharmacokinetic study revealed that ZP1, ZP2, and ZP3 had drug-like properties. [ABSTRACT FROM AUTHOR]

In this research, we synthesized new pyrimidine fused quinoline derivatives in high yields using multicomponent reaction of the 2-amino-4-hydroxyacetophenone, isopropenylacetylene, aldehydes, malononitrile or ethyl cyanoacetate, acetaldehyde and dimethylacetylene dicarboxylate in the presence of catalytic amounts of Fe3O4/KF/Clinoptilolite@MWCNTs magnetic nanocomposites using ionic liquid as green solvent at room temperature. Also, the catalytic activity of the green synthesized Fe3O4/KF/Clinoptilolite@MWCNTs MNCs was evaluated in the reduction of organic pollutants such as 4-nitrophenol (4-NP) in water at mild conditions. The results indicated that the biosynthesized NCs have very high and effective catalytic activity for organic pollutants within few seconds. The synthesized compounds have NH group in their structure and for this reason have good antioxidant activity. Also, employing Gram-positive and Gram-negative bacteria in the disk diffusion procedure confirmed the some pyrimidine fused quinoline derivatives antimicrobial effect. The results showed that synthesized compounds prevented the bacterial growth. This used procedure for preparation of pyrimidine fused quinoline derivatives has some advantages such as low reaction time, product with high yields, simple separation of catalyst and products. Green chemistry is the use of a set of principles to reduce or eliminate the use or generation of unsafe materials in the design, fabrication and applications of chemical products. Among solvents, water is a green solvents and very suitable for performing organic reaction. The present procedure avoids the use of toxic solvent. Specially fused N-heterocycles, having privileged motifs like pyrimidine and quinolines, are found in many drugs and bioactive natural products. Hybrid molecules having a pyrimidine ring fused with quinoline are also known as deazaflavins or 5-deazaisoalloxazines. [ABSTRACT FROM AUTHOR]

The present work is directed to synthesize and evaluate the antimicrobial activity of some novel 2-heteroarylchromeno[2,3-d]pyrimidines. 2-(6,8-Dimethylchromon-3-yl)-8-methoxy-4H-chromeno[2,3-d]pyrimidine-4,5(3H)-dione (4) was successfully synthesized and utilized as a building block to produce a variety of heterocyclic compounds. 2-(4-Pyrazolyl/isoxazolyl)chromeno[2,3-d]pyrimidines 5–7 were obtained from the reaction of compound 4 with hydrazine hydrate, phenylhydrazine, and hydroxylamine, respectively. Also, 2-(6-pyrimidinyl)chromeno[2,3-d]pyrimidines 8–12 were efficiently prepared from reacting compound 4 with guanidine, cyanoguanidine, thiourea, acetamidine, and benzamidine, respectively. Further, chromeno[2,3-d]pyrimidines linked diazepine 13, benzodiazepine 14, benzoxazepine 15 and benzothiazepine 16 were also synthesized. The synthesized compounds were examined for their antimicrobial efficiency. Pyrazolylchromeno[2,3-d]pyrimidines 5 and 6 showed the best activity against all kinds of microorganisms. Structures of the synthesized compounds were validated using analytical and spectral data. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase inhibition is considered a promising target for cancer treatment for its crucial role in cell cycle regulation. Pyrazolo pyrimidine derivatives were well established for their antitumor activity via CDK2 inhibition. In this research, new series of pyrazolopyrimidine derivatives (4-15) was designed and synthesised as novel CDK2 inhibitors. The anti-proliferative activities against MCF-7, HCT-116, and HepG-2 were used to evaluate their anticancer activity as novel CDK2 inhibitors. Most of the compounds showed superior cytotoxic activity against MCF-7 and HCT-116 compared to Sorafenib. Only compounds 8, 14, and 15 showed potent activity against HepG-2. The CDK2/cyclin A2 enzyme inhibitory activity was tested for all synthesised compounds. Compound 15 showed the most significant inhibitory activity with IC50 0.061 ±0.003 µM. It exerted remarkable alteration in Pre G1 and S phase cell cycle progression and caused apoptosis in HCT cells. In addition, the normal cell line cytotoxicity for compound 15 was assigned revealing low cytotoxic results in normal cells rather than cancer cells. Molecular docking was achieved on the designed compounds and confirmed the two essential hydrogen binding with Leu83 in CDK2 active site. In silico ADMET studies and drug-likeness showed proper pharmacokinetic properties which helped in structure requirements prediction for the observed antitumor activity. [ABSTRACT FROM AUTHOR]

A new series of pyrimidine derivatives are reported here as antitumor agents such as pyrimidine carboxamide linked to thiophene, pyrazole, and thiazole moieties have been synthesized from the readily available (2-cyano-N-(5-cyano-2-phenyl-6-arylpyrimidin-4-yl)acetamide (6a,b). All the new compounds were screened for their antitumor activity in vitro against a panel of three human tumor cell lines namely, hepatocellular carcinoma (liver) HepG2, colon cancer HCT-116, and mammary gland breast MCF-7. Compounds 9b, 10b, 11b, and 19b displayed a significant therapeutic activity. All the synthesized new compounds were established their structures by means of spectroscopic analysis. [ABSTRACT FROM AUTHOR]

In this research, we study here, the synthesis of 5-arylidenethiazolidin-4-one derivatives 5 which was used as a base for the synthesis of new thiazolo[4,5-d]thiopyrimidine derivatives and thiazolo[4,5-b] pyridine derivatives. New of their thioglycoside and N-glycoside derivatives were also studies. All the newly synthesized compounds exhibited high antimicrobial activity toward certain some microorganisms (bacteria and fungi). Some of these newly synthesized compounds were docked within the protein surface of 5AF1. The reports of this docking study revealed that the new compounds exhibit good antimicrobial activity. The structure of the newly synthesized compounds was characterized by spectral analysis such as IR spectrum, 1H NMR spectrum, and 13C HNMR spectrum. [ABSTRACT FROM AUTHOR]

Nowadays heterocyclic compounds containing pyrimidine scaffold attract the interest of many organic chemists due to their strong biological activity, so herein we present the synthesis of new polycyclic compounds starting from 4-chloro-9-phenyl-N-(p-tolyl)pyrimido[5',4':4,5]thieno[3,2-d][1,2,3]triazin-7-amine (1) which allowed to react with hydrazine hydrate to give hydrazinyl triazine compound (2) which subjected to some ring closure reactions using various reagents represented in triethyl orthoformate, acetyl acetone, and carbon disulfide to give compounds (3–5), respectively. Also, when the hydrazinyl compound was allowed to react with acetophenone, ethoxymethylene ethylcyano acetate, and diethyl malonate gave the derivatives (9–11), respectively. The structures of all newly synthesized compounds were confirmed using spectral analysis techniques as well as elemental analysis. Besides, four new compounds were screened for their antimicrobial activity using different strains of bacteria and fungi, and compound 5 displayed the best antimicrobial activity among all the tested compounds. [ABSTRACT FROM AUTHOR]

An unexpected efficient basic catalyzed heterocyclization reactions were carried out to build blocks of potentially bioactive 2-{pyrano[2,3-c]pyrazoles-4-ylidene}malononitrile skeleton fused with pyrazole, pyridine, pyrimidine, diazepine, chromone, pyrano[2,3-c]pyrazole, and pyrano[2,3-d]pyrimidine systems in novel molecular frames. The method depended on treatment of 6-amino-4-(4-oxo-4H-chromen-3-yl)-3-phenyl-1,4-dihydro-pyrano[2,3-c]pyrazole-5-carbonitrile (1) with different nitrogen and carbon nucleophiles in ethanolic sodium ethoxide. Possible mechanisms for the reactions were suggested. Elemental analyses and spectral techniques confirmed the structures of the isolated products. The compounds were evaluated for cytotoxic activities. Among the synthesized compounds, both 4 and 11 exhibited the most potent cytotoxicity against all used cancer cell lines. [ABSTRACT FROM AUTHOR]

A new library of different substituted aryl derivatives of isoxazole-pyrazolo[1,5-a]pyrimidine (10a–j) were prepared, confirmed their structures by 1HNMR, 13CNMR and mass spectral data. Furthermore, the preliminary anticancer activities of newly developed compounds (10a–j) were tested against four human cancer cell lines PC3 (prostate), DU-145 (Prostate), A549 (lung) and MCF-7 (breast) by utilizing of MTT method. The obtained results of were compared with standard reference etoposide. Among all, compounds (10a, 10b, 10c, 10e, 10i and 10j) displayed highest anticancer activities than standard. Predominantly, one compound 10a with 3,4,5-trimethoxy substituent on the aryl ring showed excellent activity. The molecular modeling studies indicated the interactions of synthesized compounds with SARM, and DNA via hydrogen bonds and hydrophobic interactions. [ABSTRACT FROM AUTHOR]

The electron deficient substrate; 2-[(1-chloro-3-oxoprop-1-en-1-yl)amino]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (1) was utilized as building block for construction of some novel heterocyclic rings bearing pyrimidine nucleus. β-Chloroenaldehyde derivative 1 was allowed to react with a diversity of 1,3-N,N-binucleophilic reagents producing some heterocyclic systems namely triazolo[4,3-a]pyrimidine, pyrimido[1,2-a]benzimidazole, pyrimido[1,2-a]pyrimidine and pyrimido[2,1-c][1,2,4]triazine. Reaction of β-chloroenaldehyde 1 with some 1,3-C,N-binucleophiles produced pyridines, pyrido[1,2-a]benzimidazole, pyrazolo[3,4-b]pyridine and pyrido[2,3-d]pyrimidine incorporating pyrimidine moiety through NH linkage. Condensation of β-chloroenaldehyde 1 with some cyclic active methylene compounds namely dimedone and barbituric acid afforded chromen-2-ylaminopyrimidine and pyrano[2,3-d]pyrimidine. Moreover, β-chloroenaldehyde 1 reacted with some 1,4-binucleophiles namely o-phenylenediamine, 1,6-diaminopyridone, o-aminophenol and o-aminothiophenol leading to benzodiazepine, pyrido[1,2-b][1,2,4]triazepine, benzoxazepine and benzothiazepine bearing the pyrimidine moiety through NH linkage. The antimicrobial evaluation of the synthesized compounds appeared variable inhibitory effect toward the tested microorganisms. Structures of the new synthesized products were established based on their analytical and spectral data. [ABSTRACT FROM AUTHOR]

A new series of pyrazole, pyrimidine, pyrazolo[1,5-a]pyrimidine, imidazo[1,2-b]pyrazole and pyrazolo[5,1-b]quinazoline derivatives containing indane moiety are prepared by using N-(2,3-dihydro-1H-inden-5-yl)carbonohydrazonoyl dicyanide (2) as starting material to synthetic different heterocyclic compounds (3–11) by the reaction with different bifuncation reagents. Moreover, 4-((2,3-dihydro-1H-inden-5-yl)diazenyl)-1H-pyrazole-3,5-diamine (3) was taken as a precursor to prepare different pyrazolo[1,5-a]pyrimidine derivatives (12–20). The structures of newly synthesized compounds were confirmed on the basis of their IR, 1H NMR, 13C NMR, and mass spectral data. All compounds were evaluated as anti-inflammatory activity by using carrageenan-induced rat paw edema test. In comparison to the standard drug diclofenac sodium, compounds 3, 7, 9, and 11 exhibited potent activity than standard drug. The compounds 2 and 8 showed the most significant anti- anti-inflammatory with 64.83 and 63.95% inhibition of edema. [ABSTRACT FROM AUTHOR]

Acetylation of 2-amino-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (2) using acetic anhydride afforded N-pyrimidinylacetamide derivative 3 which upon formylation using Vilsmeier-Haack reagent produced β-chloroenaldehyde derivative 4. The chemical behavior of compound 4 was investigated toward some primary amines as well as heterocyclic amines yielding the corresponding Schiff bases. Compound 4 is used as a building block for the construction of nitrogen heterocyclic compounds such as pyrazoles, pyrimidines, pyridopyrimidine and diazepine through its reaction with a diversity of bifunctional nucleophiles such as hydrazines, guanidines, 6-aminouracil and ethylenediamine. The biological activity of the synthesized compounds was investigated. Structures of the newly synthesized products were deduced on the basis of their analytical and spectral data. [ABSTRACT FROM AUTHOR]

5-(3-Chlorophenyl)-1,3,4-thiadiazol-2-amine 2 was synthesized and employed to synthesize new 1,3,4-thiadiazole and 1,3,4-thiadiazolo[3,2-a]pyrimidine derivatives via reactions with variant electrophilic reagents under solvent-free conditions. The chemical structures of these novel compounds were elucidated scrupulously by aiding elemental data and spectroscopic techniques. The synthesized compounds were evaluated for the insecticidal activity against cotton leaf worm (Spodoptera littoralis). It was realized that the insecticidal activity of 1,3,4-thiadiazolo[3,2-a]pyrimidine derivatives emerged remarkable results comparable with 1,3,4-thiadiazole derivatives against cotton leafworm (Spodoptera littoralis). [ABSTRACT FROM AUTHOR]

A series of new fist-time synthesized of thiazolyl-substituted 4-aminopyrimidine was obtained on the basis of a two-stage process including thioamidation of 4-amino-5-cyanopyrimide followed by one-pot acylation and Hantzsch synthesis in good yield (52–77%). All synthesized compounds showed a good anticancer effect in antiproliferative assay (end point) on three tumor lines A431, A549 и HT-1080 [ABSTRACT FROM AUTHOR]

Various derivatives of 5-aryl-4-imino-3-(phenylamino)-4,5-dihydroisothiazolo[3,4-d]pyrimidines (3a-f) were synthesized. The synthesis has been done through treatment of 3-amino-4-cyano-5-(phenylamino)isothiazole with various aryl isothiocyanates. The isothiazole skeleton was obtained by the reaction of malononitrile and phenyl isothiocyanate followed by chloramine treatment. Some of the synthesized dihydroisothiazolo[3,4-d]pyrimidines were tested against different cancer cell lines, including ACHN, HeLa, HL-60, MCF-7, and PC3. Malignant cells were cultured in RPMI medium and incubated with different concentrations of the mentioned compounds. Cell viability was assessed using the MTS assay. The cytotoxicities of the synthesized compounds are not significant and are probably safe for other biological use. [ABSTRACT FROM AUTHOR]

5-Acetyl-1,3,4-thiadiazolines are a versatile class of heterocycles which find wide application in medicinal and materials chemistry. The objective of this review is to describe the different strategies developed so far for the synthesis of 5-acetyl-1,3,4-thiadiazolines and their analogues as well as to highlight their reactivity in the synthesis of chemically relevant bioactive heterocyclic compounds. The first part of this review describes the diverse synthetic approaches to synthesize 5-acetyl-1,3,4-thiadiazolines based on the [4π + 2π] cycloaddition reaction of C-acetyl nitrile imines with reagents having sulfur diploarphiles. The synthetic methods have been organized on the basis of the type of sulfur reagent employed in the syntheses. In the second part, an overview of the transformations of 5-acetyl-1,3,4-thiazolines into heterocyclic compounds such as pyrazoles, thiazoles, 1,3,4-thiadiazoles, imidazoles, pyridines, and pyrimidines as well as other relevant condensed derivatives, is presented. [ABSTRACT FROM AUTHOR]

4,7-Dihydroazolo[1,5-a]pyrimidin-5-ylmethanesulfonamides are side-products of the three-component Biginelli-like reaction of aminoazoles, aldehydes and N,N-dialkyl-2-ketomethanesulfonamides. Herein, we report a straightforward synthesis of 5-sulfonamidomethyl substituted 4,7-dihydroazolo[1,5-a]pyrimidines by a two-component condensation of aminoazoles and N,N-dialkyl(cinnamoyl)methanesulfonamides in DMF at reflux. The starting N,N-dialkyl-2-ketomethanesulfonamides can be obtained by either lithiation of N,N-dialkylmethanesulfonamides and reaction with aldehydes followed by oxidation of the resulting alcohols or by Claisen condensation of N,N-dialkylmethanesulfonamides with the corresponding esters. The chemical structures of all synthesized compounds are supported by 1H and 13C NMR-spectroscopy, mass spectrometry and elemental analysis. [ABSTRACT FROM AUTHOR]

Reaction of 6-methyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxaldehyde (1) with hydroxylamine hydrochloride under different reaction conditions produced a novel pyrano[3,2-c]quinoline derivatvies 2-5. Ring opening ring closure reactions of pyrano[3,2-c]quinoline-3-carbonitrile 2 with some nitrogen nucleophiles afforded the novel 3-heteroaryl-4-hydroxyquinolines. While, treatment of carbonitrile 3 with some nitrogen nucleohilic reagents produced a diversity of annulated pyrano[3,2-c]quinolines. The chemical reactivity of the prepared pyrano[3,2-c]quinoline-3-carbonitriles 2 and 3 is widely different depending on the different reactivity of pyran-2-one and pyran-4-one moieties toward the nucleophilic reagents as well as the functional groups present in pyrone rings. [ABSTRACT FROM AUTHOR]

A novel series of pyrazolo[1,5-a]pyrimidines14a–jand pyrazolo[1,5-a]quinazolines18a, bwere synthesizedviacondensation of 5-amino-1H-pyrazoles10a, bwith 3-(dimethylamino)-1-aryl-prop-2-en-1-ones11a–eand 2-((dimethylamino)methylene)-5,5-dimethylcyclohexane-1,3-dione (15), respectively, in glacial acetic acid. Finally, treatment of10a, bwith sodium nitrite (NaNO2) afforded pyrazolo[3,4-d]triazines20a, b. Structures of compounds were confirmed by their spectral data. These compounds were screened for theirin vitrocytotoxic activities against human cancer cell lines (HepG-2 and MCF-7) using 3-[4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The results reveal that, the compounds14band14hwere the most potent in comparison with doxorubicin. The structure–activity relationship was discussed. [ABSTRACT FROM PUBLISHER]

α, β-Unsaturated carbonyl compounds2a, 2b, 3,and4were synthesized by the Knoevenagel condensation between 2-substituted quionoline-3-carboxaldehyde1aand/or1bwith active methylene compounds. In addition, the synthesis of azlactone is achieved starting from1aandN-acetylglycine. Synthesis of pyridine, pyrene, and pyrimidine derivatives6–8were accomplished via one-pot multicomponent reaction of1bwith acetyl acetone, malononitrile, and ammonium acetate; acetophenone, malononitrile, and NaOH; or acetyl acetone and urea in acidic medium. The new synthesized compounds showed good antimicrobial activities. The DFT calculations have been used to predict the electronic properties of the studied compounds. [ABSTRACT FROM PUBLISHER]

The synthesis of a new category of novel cytosine 4-thioglycoside analogs has been first accomplished. The main step of this strategy is the synthesis of sodium pyrimidine-4-thiolate through the condensation of 2-cyano-N-arylacetamides with sodium cyanocarbonimidodithioate, followed by coupling with α-bromo-sugars to afford the corresponding cytosine 4-thioglycoside analogs. The free thioglycosides were also prepared. Subsequent studies on the application of this strategy for the preparation of other potent pyrimidine thioglycosides are reported. [ABSTRACT FROM AUTHOR]

A simple and one-pot synthesis of naphthopyranopyrimidines is reported by the three-component condensation reaction of aldehydes, β-naphthol, and 1,3-dimethylbarbituric acid using ZnAl2O4nanoparticles under microwave irradiation. This flexible and nano-catalytic procedure showed good recyclability and provides a clean condensation reaction in a short reaction time. [ABSTRACT FROM PUBLISHER]

This review deals with the synthesis and reactions of 5-acetylthiazoles. Some of these reactions have been used successfully for the production of biologically important compounds. The main purpose of this review is to present a survey of the literature on the chemistry of 5-acetylthiazoles and to provide useful and up-to-date information on their applications because these compounds have not been previously reviewed. [ABSTRACT FROM AUTHOR]

Novel [1,2,4]triazolo[4,3-c]pyrimidine-8-carboxamides were synthesized via oxidative cyclization of hydrazono-1,6-dihydropyrimidine-5-carboxamide intermediates by the application of iodobenzenediacetate as a sole cyclizing agent. Here, we report a one-pot sequential strategy to generate the corresponding triazolopyrimidines by condensation of prepreparedα-acylketene dithioacetals and arylamidines. Moreover, this process describes the application of presynthesized arylamidines, which omits the Suzuki–Miyaura cross-coupling reaction and hence provides metal-free organic synthesis in an atom- and step-economical fashion. [ABSTRACT FROM PUBLISHER]

A simple and efficient pathway to conjugate monosaccharides to thienopyrimidines via click chemistry establishing a 1,2,3-triazole linker was reported. Potential pharmaceutical interest is envisaged for the expected target products. Starting from a 2-isothiocyanate-thiophene-3-carboxylate, an allylthiourea was obtained with allylamine, cyclized andS-propargylated to give a thienopyrimidine–alkyne core. Click reaction with tetraacetyl-1-azidoglucose was successful to give the target conjugate with one sugar unit. When propargylamine was used in the first step, the expected thiourea cyclized via the alkyne moiety leading to pyrimido[2,1-b][1,3]thiazine. [ABSTRACT FROM PUBLISHER]

Synthesis of selectively N-3-substituted pyrimidine nucleobases or pyrimidinones has always been a challenge because of poor regioselectivity and chemoselectivity. In this article we demonstrate a single-step, de novo synthesis of selectively N-3-substituted modified pyrimidinones. We have developed a microwave-assisted methodology for direct, chemoselective alkylation, benzylation, and arylation of C-5 and C-6 substituted pyrimidine nucleobases selectively at the N-3 position. The reactions were found to proceed, with high efficiency, without the requirement of solvent and were complete within 10–15 min of irradiation. The efficiency of the method was further improved by addition of a Lewis acid, which not only increases the yield significantly but also accelerates the reaction rate. [ABSTRACT FROM PUBLISHER]

In order to find the new potent CK2 inhibitors the 60 derivatives of 2-aminopyrimidinone and their 6-aza-substituted analogs were synthesized and tested in vitro. Among them, the most efficient inhibitor 2-hydroxy-5-[4-(4-methoxyphehyl)-6-oxo-1,6-dihydropyrimidin-2-ylamino] benzoic acid was identified (IC50 = 1.1 μM). The structure--activity relationship study of newly synthesized derivatives was carried out and their binding mode with adenosine triphosphate-acceptor site of CK2 was proposed. [ABSTRACT FROM AUTHOR]

The aim of the present work was to search for identification of novel reactive oxygen species (ROS) scavengers by testing new fused chromenopyrimidinethiones, which was synthesized using Fe3O4nanoparticles. The new compounds were also tested for their cytotoxic activity. The obtained results showed that the incorporated pyrimidinethione moiety significantly increase antioxidant activity. In conclusion, the study of the pharmacological properties of the new chromenopyrimidinethiones allowed establishing new structure–activity relationships for splitting antioxidant and cytotoxic activity of these compounds. [ABSTRACT FROM AUTHOR]

The preparation of a series of novel chromone-fused cytosine analogues, i.e., chromeno[2,3-d]pyrimidines has been carried out from substituted 2-amino-4-oxo-4H-chromene-3-carbonitriles with urea, thiourea, and guanidine under different reaction conditions. These chromone-fused cytosine analogues were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv strain and different microbial pathogenic strains in cell culture for their structure–activity relationships, respectively. Among the synthesized compounds,2d,3a,and4eshowed better results against Mycobacterium tuberculosis H37Rv. The compounds2a,2b,and3ashowed potential antibacterial activity against E. coli and P. aeruginosa, while the majority of compounds were found to be active against S. aureus as compared to ampicillin. The synthesized cytosine analogues having an imine (–C&dbnd;NH) have been less sensitive to the bacterial and fungal strains but have a more beneficial effect on Mycobacterium tuberculosis H37Rv. [ABSTRACT FROM PUBLISHER]

3,4-Dihydropyrimidin-2(1H)-thione derivatives undergo a chemoselective reaction with dialkylacetylenedicarboxylate in the presence of triphenylphosphine lead to the corresponding stable heterocyclic phosphorus ylides in good yield. In this method, a mixture of water/acetone as a green solvent was used. [Supplemental materials are available for this article. Go to the publisher's online edition ofPhosphorus, Sulfur, and Silicon and the Related Elementsto view the following free supplemental files: Additional figures] [ABSTRACT FROM PUBLISHER]

Herein we report the synthesis and characterization oftrans-[RuIICl2(PPh3)3] with potentially tridentate Schiff bases derived from 5,6-diamino-1,3-dimethyl uracil (H2ddd) and two 2-substituted aromatic aldehydes. In the diamagnetic ruthenium(II) complexes,trans-[RuCl(PPh3)2(Htdp)] (1) {H2tdp = 5-((thiophen-3-yl)methyleneamino)-6-amino-1,3-dimethyluracil} andtrans-[RuCl(PPh3)2(Hsdp)] (2) {H2sdp = 5-(2-(methylthio)benzylideneamino)-6-amino-1,3-dimethyluracil}, the Schiff base ligands (i.e. Htdp and Hsdp) act as mono-anionic tridentate chelators. Upon reacting 5-(2-hydroxybenzylideneamino)-6-amino-1,3-dimethyluracil (H3hdp) with the metal precursor, the paramagnetic complex,trans-[RuIVCl2(ddd)(PPh3)2] (3), was isolated, in which the bidentate dianionic ddd co-ligand was formed by hydrolysis. The metal complexes were fully characterized via multinuclear NMR-, IR-, and UV–Vis spectroscopy, single crystal XRD analysis and conductivity measurements. The redox properties were probed via cyclic voltammetry with all complexes exhibiting comparable electrochemical behavior with half-wave potentials (E½) at 0.70 V (for1), 0.725 V (for2), and 0.68 V (for3)versusAg|AgCl, respectively. The presence of the paramagnetic metal center for3was confirmed by ESR spectroscopy. [ABSTRACT FROM PUBLISHER]

A Pd-mediated hydrogenation of ethyl 6-azidomethyl-1,2,3,4-tetrahydro-4-R-2-oxo-5-pyrimidinecarboxylates leads to the corresponding ethyl 6-aminomethyl1,2,3,4-tetrahydro-4-R-2-oxo-5-pyrimidinecarboxylates. The latter react with bis(trichloromethyl)carbonate, yielding the title ethyl 1,2,3,5,6,7-hexahydro-7-R-3,5-dioxoimidazo[1,5-c]pyrimidine-8-carboxylates. Supplemental materials are available for this article. Go to the publisher's online edition ofSynthetic Communications® to view the free supplemental file. [ABSTRACT FROM AUTHOR]

Silica-supported sulfonic acid–functional ionic liquid (Si-[SbSipim][PF6]) was found to be an effective catalyst for the synthesis of 3,4-dihydropyrimidine-2-(1H)-ones via a one-pot, three-component Biginelli reaction. The catalyst could be easily separated and reused six times without noticeable reduction inactivity. The process was simple and proceeded in excellent yields. Supplemental materials are available for this article. Go to the publisher's online edition ofSynthetic Communications® to view the free supplemental file. [ABSTRACT FROM AUTHOR]

A simple, efficient, and ecofriendly procedure was developed for the synthesis of 2-substituted 1,4,5,6-tetrahydropyrimidine derivatives catalyzed by N-bromosuccinimide using ultrasonic irradiation in aqueous medium. Prominent advantages of this new method are good yields, aqueous medium, short reaction times, and easy workup procedure. The compounds were characterized by infrared, NMR, liquid chromatography–mass spectrometry, and elemental analyses. [ABSTRACT FROM AUTHOR]

A rapid synthesis of a series of new 5,6-dimethyl-7-phenyl-2-alkyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidinones and 5,6-dimethyl-7-benzyl-2-alkyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidinones was accomplished in good yields using microwave irradiation under base catalysis. [ABSTRACT FROM AUTHOR]

The article focuses on the expeditious synthesis of dihydro-1,2,4-triazolo[1,5-a] pyrimidines and tetrahydro-1,2,4-triazolo[5,1-b]quinazolin-8(4H)-ones. It says that grinding solid reactants using mortar and pestle has been performed to approach to achieve the goal of the study. Study used one-pot multi-component reactions (MCRs) a powerful tool to assemble large libraries of the biologically active compounds. Study reveals that the ionic liquid may be recovered by water evaporation under the vacuum after washing with diethyl ether and drying in oven at 90 °Celsius (C).

A centrosymmetric phenolate oxygen bridged dinuclear copper(II) complex [Cu2(L1)2(N3)2] (1) and a mononuclear zinc(II) complex [Zn(L2)(NCS)2] (2), where HL1 = 2-[1-(pyridin-2-ylmethylimino)ethyl]phenol and L2 = (1-pyridin-2-ylethylidene)pyridin-2-ylmethylamine, were synthesized and structurally characterized by physicochemical methods and single-crystal X-ray diffraction. The Cu atom in (1) is five-coordinated in a slightly distorted square pyramidal geometry, and the Zn atom in (2) is five-coordinated in a severely distorted square pyramidal geometry. [ABSTRACT FROM PUBLISHER]

Reaction of (dicyanomethylidene-hydrazino)benzoic acids with chloroacetonitrile, under basic conditions, gave cyanomethyl-3-(7-amino-3,5-dicyano-1H-pyrazolo[4,3-d]pyrimidin-1-yl-benzoates and para-substituted cyanomethyl benzoates, in addition to the expected cyanomethyl 3-(4-amino-3,5-dicyano-1H-pyrazol-1-yl)-benzoates. [ABSTRACT FROM AUTHOR]

A series of 3-cyano-6,7-diarylpyrazolo[1,5-a]pyrimidines have been synthesized directly from the 5-amino-4-cyano-1H-pyrazole and isoflavones. The target compound was obtained by a condensation reaction. Structures of compounds were demonstrated by Fourier transform infrared, NMR, and elemental analysis. The advantages of this synthetic route are simple operation, mild reaction conditions, and good yields. [ABSTRACT FROM AUTHOR]

The one-pot reaction ofglyoxylic acid hydrate withdiphenylphosphine and a heretocyclic primary amine in methanol results in formation of first examples of N-hererocyclic α-diphenylphosphinoglycines bearing imidazo[4,5-d]-pyrimidine-6-yl, 4,6-dimethylpyrimidin-2-yl, pyridine-2-yl and pyridine-3-yl substituents. [ABSTRACT FROM PUBLISHER]