<i>β</i>-Oxoanilides in Heterocyclic Synthesis: Synthesis and Antimicrobial Activity of Pyridines, Pyrans, Pyrimidines and Azolo, Azinopyrimidines Incorporating Antipyrine Moiety

Condensation of β-Oxoanilide 1 with active methylene derivatives 2a,bafforded the pyridine derivative 5, and with crotononitrile afforded the pyridine 8. Compounds 9 and 11a-c were obtained by reaction of 1 with malononitrile dimer and arylidinemalononitrile 10a-10c. In contrast, when compound 1 reacted with ethoxymethylen malononitrile afforded the pyridine derivative 13. On the other hand, treatment of 1 with anthranilic acid gave the quinoline derivative 14. Also, reactions of 1 with isothiocyanate derivatives afforded compounds 16-18. The reaction of 1 with chalcone derivative afforded the pyridine derivative 22. Treatment of compound 1 with thiourea produced pyrimidine derivative 23. Furthermore, compound 1 converted into pyrimidinethione 24a and pyrimidinone 24b on treatment with a mixture of aromatic aldehydes and thiourea or urea respectively. Reaction of 24a with hydrazonyl halide, thiosemicarbazide and arylidinecyanothioacetamide afforded compounds 26, 28 and 29. Compound 29 was treated with chloroacetonitrile to afford compound 30. Six compounds from the newly synthesized were screened for antibacterial and antifungal activity against bacteria staphylococcus aureus, bacillus cereus and klebsiella pneumonia and fungi aspergillus flavus and aspergillus ochraceous, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, 1H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.

Synthesis of 2-Arylimidazo[l, 2-a]pyrimidines in Ionic Liquids

Room temperature ionic liquids were used as a "green" recyclable alternative to conventional solvents in the synthesis of pharmaceutically useful compounds 2-arylimidazo[1, 2-a] pyrimidines through Tschotschibabin reaction of a-bromoacetophenones with 2-aminopyrimidine in good yields.

Tetra-n-butylammonium Hydroxide:an Efficient Catalyst for N-Alkylation of Pyrimidines and Purines

An efficient procedure for N-alkylation of pyrimidines and purines in the presence of tetra-n-butylammonium hydroxide（TBAH） is described. The method is very practical and the alkylation can occur at room temperature and the yields of the N-alkyl pyrimidines and purines were found to be excellent.

Facile Syntheses of New Pyrazolo[1,5-a]pyrimidines Derivatives via Reactions of Enaminones with Aminopyrazole

Ethyl 7-aryl-2-benzyhhiopyrazolo [ 1,5-a ] pyrimidine-3-carboxylates （3a-3f） were conveniently synthesized through the reactions of enaminones with 5-amino-3-benzyhhio4-ethoxycarbonyl-1 H-pyrazole in good yields and high regioselectivity. The structures of the new compounds were fully characterized by spectroscopic measurmehts, elemental analysis and X-ray diffraction analysis. A plausible reaction mechanism for the formation of the title compounds was also presented.

Synthesis of 5,7-Dimethyl-2-(5-Substituted-1,3,4-Oxadiazole-2-yl)- Methylenethio-1,2,4-Triazolo[1,5-a]Pyrimidines as Potential Fungicides

A series of diheterocyclic compounds containing 1,2,4-triazolo [1,5-a]pyrimidine and 1, 3,4-oxadiazole were designed and synthesized starting from 2-mercapto-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine. The structure of all compounds prepared were confirmed by H-1 NMR spectroscopy and elemental analysis. The preliminary bioassay indicated that the title compounds displayed good fungicidal activity against Rhizoctonia solani.

One-Pot Synthesis of Pyrido[2,3-d]pyrimidines Catalyzed by Bismuth(III)Triflate

Synthesis of uracil derivatives, such as pyrido[2,3-d]pyrimidine, is very important for the pharmaceutical industry due to their many biological activities. In our continuing efforts into the development of new synthetic strategies for the preparation of heterocyclic compounds in this study, we performed reflux reactions with the catalyst Bi(OTf)3 by using a one-pot, threecomponent method. The one-pot, three-component condensation of 6-amino-1,3-dimethyluracil, with arylaldehydes and malononitrile to generate a series of 7-aminopyrido[2,3-d]pyrimidine-6-carbonitrile derivatives has been carried out in the presence of bismuth triflate as a green and reusable catalyst.

Iron-catalyzed[4+2]annulation of amidines with α,β-unsaturated ketoxime acetates toward 2,4,6-trisubstituted pyrimidines

An iron-catalyzed[4+2]annulation of amidines with α,β-unsaturated ketoxime acetates is described.This strategy employs amidines as CN units and provides a new protocol for the construction of 2,4,6-trisubstituted pyrimidines under batch and continuous flow conditions in moderate to good yields,exhibiting good functional group tolerance,scalability and operational simplicity.

Synthesis of novel isoxazolyl bis-thiazolo[3,2-a]pyrimidines

A new synthetic strategy for the synthesis of novel 3-（3-（3-methyl-4-nitroisoxazol-5-yl）-2-phenyl-1-（5,7-diaryl-7H-thia- zolo[3,2-a]pyrimidin-3-yl）propyl）-5,7-diaryl-7H-thiazolo[3,2-a]pyrimidines （7a-i） analogues is described. Reaction of 3-（2- （3-methyl-4-nitroisoxazole-5-yl）-l-phenylethyl）pentane-2,4-dione （3） with two moles of thiourea in presence of iodine and CuO afforded 4-（1-（2-aminothiazol-4-yl）-3-（3-methyl-4-nitroisoxazol-5-yl）-2-aryl propylthiazol-2-amine （5）. Compound 5 on reaction with two moles of chalcone （6） furnished novel 3-（3-（3-methyl-4-nitroisoxazol-5-yl）-2-phenyl-1-（5,7-diaryl-7H-thiazolo[3,2- a]pyrimidin-3-yl）propyl）-5,7-diaryl-7H-thiazolo[3,2-a ]pyrimidines （Ta-i）.

May the Force Be with You: Metabolism of Arginine and Pyrimidines

＂Why do arginine and pyrimidines have to be considered together？＂ This was the question I asked when I was invited by Barbara Zimmermann to attend the 23rd Intemational Conference on Arginine and Pyrimidines （ICAP） three years ago. The meeting was held in the summer of 2012 at Bogota, Columbia, known as the ＂the Athens of South America＂. I am not alone in wanting to know more about the relationship between arginine and pyrimidines. Last summer, when ! was organising the next ICAP meeting at Oxford （Aughey et al., 2014）, one of my colleagues asked me, ＂Why such a weird name for a conference？＂ I am not sure if I had given her a satisfying answer and I was enthused to find out what the reasons may be.

A review on potential heterocycles for the treatment of glioblastoma targeting receptor tyrosine kinases

Glioblastoma,the most aggressive form of brain tumor,poses significant challenges in terms of treatment success and patient survival.Current treatment modalities for glioblastoma include radiation therapy,surgical intervention,and chemotherapy.Unfortunately,the median survival rate remains dishearteningly low at 12–15 months.One of the major obstacles in treating glioblastoma is the recurrence of tumors,making chemotherapy the primary approach for secondary glioma patients.However,the efficacy of drugs is hampered by the presence of the blood-brain barrier and multidrug resistance mechanisms.Consequently,considerable research efforts have been directed toward understanding the underlying signaling pathways involved in glioma and developing targeted drugs.To tackle glioma,numerous studies have examined kinase-downstream signaling pathways such as RAS-RAF-MEKERK-MPAK.By targeting specific signaling pathways,heterocyclic compounds have demonstrated efficacy in glioma therapeutics.Additionally,key kinases including phosphatidylinositol 3-kinase(PI3K),serine/threonine kinase,cytoplasmic tyrosine kinase(CTK),receptor tyrosine kinase(RTK)and lipid kinase(LK)have been considered for investigation.These pathways play crucial roles in drug effectiveness in glioma treatment.Heterocyclic compounds,encompassing pyrimidine,thiazole,quinazoline,imidazole,indole,acridone,triazine,and other derivatives,have shown promising results in targeting these pathways.As part of this review,we propose exploring novel structures with low toxicity and high potency for glioma treatment.The development of these compounds should strive to overcome multidrug resistance mechanisms and efficiently penetrate the blood-brain barrier.By optimizing the chemical properties and designing compounds with enhanced drug-like characteristics,we can maximize their therapeutic value and minimize adverse effects.Considering the complex nature of glioblastoma,these novel structures should be rigorously tested and evaluated for their efficacy and safety profiles.

One-pot synthesis of novel pyrido[2,3-d]pyrimidines using HAp-encapsulated-γ-Fe_2O_3 supported sulfonic acid nanocatalyst under solvent-free conditions

Novel pyrido[2,3-d]pyrimidine derivatives were synthesized through a one-pot three-component approach using HAp-encapsulated-γ-Fe2O3[γ-Fe2O3@HAp-SO3H]catalyzed condensation of 6-arnino-2-（methylthio or ethylthio）pyrimidin-4（3H）-one,Meldrum＇s acid and aryl aldehydes at 60 ℃ and under solvent-free conditions.In this protocol the use of nanocatalyst provided a green,useful and rapid method to generate the products in short reaction times and excellent yields（88%-94%）.

Base mediated direct C–H amination for pyrimidines synthesis from amidines and cinnamaldehydes using oxygen as green oxidants

A direct metal-free C-H amination reaction of cinnamaldehydes and amidines to realize the synthesis of polysubstituted pyrimidines was developed in the presence of base. This greener synthetic methodology provides a straightforward approach to the synthesis of a variety of pyrimidine derivatives under mild reaction condition using oxygen as sole oxidants.

Palladium-catalyzed amination of chloro-substituted 5-nitropyrimidines with amines

A concise and efficient approach was developed for the synthesis of mono-substituted and di-substituted pyrimidines products via palladium-catalyzed amination of chloro-substituted 5-nitropyrimidines and amines. This synthetic methodology can produce various di-substituted pyrimidines in high yields with good functional group tolerance, and provide a complementary tool for the syntheses of important intermediates of nucleosides and purines with bioactivities.

Three-component synthesis of imidazo[1,2-c]pyrimidines using silica sulfuric acid(SSA)

This letter describes a simple and efficient synthesis of 3-（cyclohexylamino）-7-hydroxy-2-arylimi- dazo[1,2-c]pyrimidin-5（6H）-one via a one-pot three-component reaction of cyclohexyl isocyanide, an aldehyde, and 4-amiopyrimidine-2,6-diol in the presence of a catalytic amount of SSA.

Synthesis of substituted pyrazolo[1,5-α]pyrimidines

Condensation of 3-amino-4-cyanopyrazole (1) with ethylacetoacetate, ethyl cyanoacetate, diethyl malonate and acetylacetone afforded pyrazolo[1,5-a]pyrimidine derivatives (2-8a). Other compounds (8b-h) of this ring system were obtained by treatment of 1 with arylidenemalononitrile and ethylarylidenecyanoacetate. And the reaction of compound (1) with activated acetylenes yeilded pyrazolo[1,5-a]pyrimidine derivatives (11a-b).

Synthesis and cytotoxic activity of novel 2,6-disubstituted-4-morpholinothieno[3,2-d]pyrimidines as potent anti-tumor agents

A series of 2,6-disubstituted-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and their cytotoxic activity against H460, HT-29, MDA-MB-231, U87MG and H1975 cancer cell lines were evaluated in vitro. Most of the target compounds exhibited moderate to excellent activity to the tested cell lines. The most promising compound 23 （0.84 μmol/L, 0.23 μmol/L, 2.52 μmogL, 1.80 μmol/L） was 1.0, 2.9, 29.3 and 4.3 times more active than GDC-0941 （0.87 μ mol/L, 0.66μmol/L, 73.8 μmol/L, 7.77 μmol/L） against H460, HT-29, MDA-MB-231 and U87MG cell lines, respectively.

Synthesis and characterization of pyrimidines analogues as anti-Alzheimer's agents

Pyrimidine derivatives have been reported as neuroprotective agents useful for the treatment of various neurodegenerative disorders. In the present study, several pyrimidine analogues have been evaluated as neuroprotective agents in Morris water maze model. It was observed that pyrimidine derivatives 8–17 considerably improve learning, memory, and movement deficits in animal models. Biochemical estimations of brain serum of treated animals revealed suppression of oxidative and nitrosative stress, acetylcholinesterase activity, and other parameters which leads to neurodegeneration of brain. Of all the pyrimidine derivatives, thiomorpholine derivative 8 and piperazine ethanol derivative 17 were found to be the most active neuroprotective agents and produced effects comparable to standard drug rivastigmine in terms of behavioral, biochemical, and molecular aspects.

Synthesis and antitumor activity of α-aminophosphonate derivatives containing thieno[2,3-d]pyrimidines

Two series of thieno[2,3-d]pyrimidine derivatives were designed and synthesized, in which bioactive α-aminophosphonate subunits were introduced at the N3 position through an N-N bond connection. The in vitro cytotoxic activity of the novel compounds was tested against human esophageal carcinoma cells （EC109）, human hepatocarcinoma cells （HepG2）, human gastric carcinoma cells （MGC-803）, respectively, by the MTT method. The evaluation results revealed that compounds fimb, 6mf, 6mg, 6rid and 6nh exerted the most potent inhibition against HepG2, MGC-803 and EC109 cells, respectively. In particular, compound 6rag presented excellent inhibitory effect against HepG2 （91.2%） and MGC-803 （94.4%） cells.

Synthesis and antitumor activity of some new pyrazolo[1,5-α]pyrimidines

New series of pyrazolo[1,5-α]pyrimidine derivatives 7a-i,11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines,namely colorectal carcinoma（HCT116）,prostate adenocarcinoma（PC-3） and liver carcinoma（HepG-2） using MTT cytotoxicity assay at 100 μg/mL.Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells.Whereas,compounds 7d and 11 a showed better antitumor activity than the rest of the compounds against both cell lines.A structure-activity relationship（SAR） has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data（MS,IR,^1H NMR and ^13C NMR） and elemental analysis.

Reaction of Enaminones with Aminopyrazoles： Synthesis,Structures and Bioactivities of 7-Aryl-3-cyano-2-substituted Pyrazolo[1,5-a]pyrimidines

The condensation reactions of 5-amino-4-cyano-3-substituted-1H-pyrazole 2 or 3 with enaminones 1 in the presence of glacial acetic acid gave twelve new 7-aryl-3-cyano-2-substituted pyrazolo[1,5-a]pyrimidines 4 and 5 at room temperature. Their structures were characterized by elemental analysis, IR and 1H NMR. The structure of 4a was further confirmed by X-ray crystallography analysis. A plausible reaction mechanism for the formation of the title compounds was also proposed. The bioassay tests showed that compounds 4a, 4e, 4e, 4f, 5a and 5d possessed moderate herbicidal activity.