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A series of novel 4-(aryl)-benzo[4,5]imidazo[1,2- a ]pyrimidine-3-carbonitriles were obtained through the Povarov (aza-Diels-Alder) and oxidation reactions, starting from benzimidazole-2-arylimines. Based on the literature data and X-ray diffraction analysis, it was discovered that during the Povarov reaction, [1,3] sigmatropic rearrangement leading to dihydrobenzimidazo[1,2- a ]pyrimidines took place. The structures of all the obtained compounds were confirmed based on the data from 1 H- and 13 C-NMR spectroscopy, IR spectroscopy, and elemental analysis. For all the obtained compounds, their photophysical properties were studied. In all the cases, a positive emission solvatochromism with Stokes shifts from 120 to 180 nm was recorded. Aggregation-Induced Emission (AIE) has been illustrated for compound 6c using different water fractions (fw) in THF. The compounds 6c and 6f demonstrated changes in emission maxima or/and intensities after mechanical stimulation.

Prevention of the formation of advanced glycation end-products (AGEs) is a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In these terms, new synthetic approaches to 6-nitroazolo[1,5-a]pyrimidines have been developed on the basis of the promising antiglycation activity of their structural analogues, such as azolo[5,1-c][1,2,4]triazine-4(1H)-ones. A number of nitroazolopyrimidines were obtained by using nitration, chlorodeoxygenation, and amination reactions, and their antidiabetic properties were elucidated in vitro. It was shown that triazolo[1,5-a]pyrimidine-7(4H)-ones exhibit a higher antiglycation activity than the corresponding 7-alkylamino analogs and aminoguanidine, as the reference compound. It is suggested that this kind of activity can be associated with the chelating properties possessed by the synthesized 6-nitro-7-oxoderivatives. Furthermore, the compounds obtained were tested for their inhibitory activity against dipeptidyl peptidase 4 (DPP4), glycogen phosphorylase, and α-glucosidase in vitro, but their activities proved to be significantly inferior to those of the reference compounds., (© 2017 Deutsche Pharmazeutische Gesellschaft.)

A facile two-step synthetic approach to fluorinated and non-fluorinated 5-aryl-4-(5-nitrofuran-2-yl)-pyrimidines from readily available 5-bromo-4-(furan-2-yl)pyrimidine has been developed. All synthesized compounds were screened in vitro for their antibacterial activities against twelve various bacterial strains. It is demonstrated that some of these compounds exhibited significant antibacterial activities against strains Neisseria gonorrhoeae and Staphylococcus aureus, comparable and even higher with that commercial drug Spectinomycin., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Various 5-(fluoroaryl)-4-(hetero)aryl substituted pyrimidines have been synthesized based on the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SN(H)) reactions starting from commercially available 5-bromopyrimidine and their antitubercular activity against Mycobacterium tuberculosis H37Rv has been explored. The outcome of the study disclose that, some of the compounds have showed promising activity in micromolar concentration against Mycobacterium tuberculosis H37Rv, Mycobacterium avium, Mycobacterium terrae, and multidrug-resistant strains isolated from tuberculosis patients in Ural region (Russia). The data concerning the 'structure-activity' relationship for fluorinated compounds have been discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SN(H)) reactions proved to be a convenient method for the synthesis of C(4) and/or C(5) mono(thienyl) and di(thienyl) substituted pyrimidines from commercially available 5-bromopyrimidine. All new pyrimidines were found to be active in micromolar concentrations in vitro against H37Rv, avium, terrae, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The data for acute in vivo toxicity in mice have been obtained for these compounds which appear to be promising antitubercular agents., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SN(H)) reactions proved to be a convenient method for the synthesis of 5-styryl-4-(hetero)aryl substituted pyrimidines from commercially available 5-bromopyrimidine. All intermediate 5-bromo-4-(hetero)aryl substituted pyrimidines and also the targeted 5-styryl-4-(hetero)arylpyrimidines were found to be active in micromolar concentrations in vitro against Mycobacterium tuberculosis H37Rv, avium, terrae, and multi-drug-resistant strain isolated from tuberculosis patients in Ural region (Russia). It has been found that some of these compounds possess a low toxicity and have a bacteriostatic effect, comparable and even higher with that of first-line antituberculosis drugs., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Hypercytokinemia, or cytokine storm, often complicates the treatment of viral and bacterial infections, including COVID-19, leading to the risk of thrombosis. However, the use of currently available direct anticoagulants for the treatment of COVID-19 patients is limited due to safety reasons. Therefore, the development of new anticoagulants remains an urgent task for organic and medicinal chemistry. At the same time, new drugs that combine anticoagulant properties with antiviral or antidiabetic activity could be helpfull in the treatment of COVID-19 patients, especially those suffering from such concomitant diseases as arterial hypertension or diabetes. We have synthesized a number of novel substituted azoloazines, some of which have previously been identified as compounds with pronounced antiviral, antibacterial, antidiabetic, antiaggregant, and anticoagulant activity. Two compounds from the family of 1,2,4-triazolo[1,5-a]pyrimidines have demonstrated anticoagulant activity at a level exceeding or at least comparable with that of dabigatran etexilate as the reference compound. 7,5-Di(2-thienyl)-4,5-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine has shown the highest ability to prolong the thrombin time, surpassing this reference drug by 2.2 times. This compound has also exhibited anticoagulant activity associated with the inhibition of thrombin (factor IIa). Moreover, the anticoagulant effect of this substance becomes enhanced under the conditions of a systemic inflammatory reaction. [ABSTRACT FROM AUTHOR]

A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and its (S)-enantiomer attached via a 6-aminohexanoyl fragment were synthesized by the reaction of nucleophilic substitution of chlorine in various chloropyrimidines. The structures of the synthesized compounds were confirmed by 1H, 19F, and 13C NMR spectral data. Enantiomeric purity of optically active derivatives was confirmed by chiral HPLC. Antiviral evaluation of the synthesized compounds has shown that the replacement of purine with a pyrimidine fragment leads to a decrease in the anti-herpesvirus activity compared to the lead compound, purine conjugate. The studied compounds did not exhibit significant activity against influenza A (H1N1) virus. [ABSTRACT FROM AUTHOR]

A series of [1,2,4]triazolo[1,5‐a]pyrimidine‐cored push‐pull compounds, bearing ethynyl moieties, was effectively prepared using transition‐metal‐free strategy involving the direct C−H functionalization of [1,2,4]triazolo[1,5‐a]pyrimidine scaffold with the Grignard‐Iocich reagents (ethynylmagnesium bromides). The basic optical and electrochemical properties of the synthesized derivatives were studied and gave grounds to consider the obtained compounds as promising UV dyes with high quantum yields. [ABSTRACT FROM AUTHOR]

A reaction of 3-oxobutanoyl-containing podands with thiophene-2-carbaldehyde (or benzaldehyde) and 3-amino-1,2,4-triazole gave podands featuring a 4,7-dihydro[1,2,4]triazolo[1,5-а]pyrimidine motif. It was established that the process was accompanied by the formation of [4,3-а]-isomers, which occurred in a slight excess during the synthesis of a podand containing a phenyl group at position 7 and, on the other hand, were observed as the minor products during the synthesis of podands bearing a thiophen-2-yl substituent. Trace amounts of monosubstituted podands were also detected, containing a free hydroxy group along with the triazolodihydropyrimidine pharmacophore. [ABSTRACT FROM AUTHOR]

A sequence of microwave-assisted Suzuki cross-coupling reaction and bromination with N-bromosuccinimide was used for the synthesis of 3,3'-(5,5'-{5-[5-(9-ethyl-9H-carbazol-3-yl)-3-hexylthiophen-2-yl]pyrimidine-4,6-diyl}bis(thiophene-5,2-diyl))bis(9-ethyl-9H-carbazole). The obtained compound was characterized with regard to its optical properties, as well as possible applications in sensors for nitroaromatic compounds in acetonitrile solutions and in vapor phase. [ABSTRACT FROM AUTHOR]

Data spanning the period 2000-2017 on the direct C-H functionalization of pyrimidines are collected and discussed in this review. This demonstrates the surge of interest and creativity that this field of chemistry has experienced during the last two decades. Plausible applications of highly functionalized pyrimidines are also discussed. 1 Introduction 2 Transition-Metal-Catalyzed C-H Functionalization of Pyrimidine Derivatives 3 Transition-Metal-Free Direct C-H Functionalization of Pyrimidine Derivatives 4 Deprotonative Metalation of Pyrimidine Derivatives 5 Conclusions. [ABSTRACT FROM AUTHOR]

A convenient synthetic route to novel thienoacene systems bearing a fused pyrimidine ring has been advanced. The commercially available 5-bromopyrimidine was used as the starting material to obtain various dithienoquinazoline systems through nucleophilic aromatic substitution of hydrogen (the SNH reaction), Suzuki cross-coupling, and oxidative photocyclization. The redox and optical properties of some of the new compounds have been investigated. The data obtained show the potential of dithienoquinazoline systems in organic electronic applications. [ABSTRACT FROM AUTHOR]

[Display omitted] The Buchwald–Hartwig cross-coupling of 5-bromo-4-(furan-2-yl)pyrimidine with various anilines afforded the corresponding new 5-(arylamino)pyrimidines, the reaction being accelerated by microwave irradiation. Most of the obtained compounds proved to possess a high bacteriostatic in vitro effect against Mycobacterium tuberculosis H 37 Rv, Neisseria gonorrhoeae , and Staphylococcus aureus including Methicillin-resistant strain, which is stronger than that of the commercial drug Spectinomycin. [ABSTRACT FROM AUTHOR]

Novel D–π–A–π–D type pyrimidine-based dyes, possessing (hetero)aryl electron-donating groups in 2,4-positions were synthesized, and their photophysical properties were investigated by using absorption and emission spectral analyses. All dyes proved to exhibit a strong emission solvatochromism with quantum yields up to 0.96, depending on their molecular structure and solvent polarity. The compounds have been established to undergo a reversible protonation, directed at nitrogen atoms of the pyrimidine ring, and these phenomena are associated with dramatic color changes. In addition, fluorophores 5a-d show a high sensitive response for nitroaromatic traces in solutions or real-time detection of their vapors in air. These findings indicate that the compounds obtained can be regarded as excellent fluorophores for fluorescent material applications. [ABSTRACT FROM AUTHOR]

(Hetero)arylation of [1,2,4]triazolo[1,5- a ]pyrimidine through the direct nucleophilic C H functionalization of the C-7 and C-5 positions has been implemented. The regioselective addition of a (het)aryl magnesium bromide to C-7 of 6-bromo-[1,2,4]triazolo[1,5- a ]pyrimidine, followed by eliminative aromatization of the intermediate σ H -adducts, has afforded 7-(hetero)aryl-substituted [1,2,4]triazolo[1,5- a ]pyrimidines (the S N H reaction, proceeding according to the “addition-elimination” scheme). A second treatment with a Grignard reagent has resulted in the C-5 σ H -adducts, which have been oxidized while being N -magnesium salts into [1,2,4]triazolo[1,5- a ]pyrimidines, bearing various combinations of (hetero)aromatic substituents at C-5 and C-7 (the S N H process, realizing via the “addition-oxidation” scheme). As a result of optical and electrochemical studies, the obtained compounds have proved to be promising luminescent dyes and push-pull systems. [ABSTRACT FROM AUTHOR]

A series of D–π–A–π–D type dyes based on pyrimidines, bearing thiophene linkers, have been studied as sensing fluorophores. Fluorescence studies have demonstrated that the emission of all derivatives is sensitive to the presence of 2,4,6-trinitrotoluene (TNT) and other nitroaromatic compounds (NACs), in their acetonitrile solutions. The detection limits of fluorophores to NACs proved to be in the range from 10 −4 to 10 −6 mol/L. The time-resolved fluorescence measurements and theoretical investigation into the quenching mechanism in the presence of fluorophore has been performed. The two types of sensor prototypes for handheld sniffer «Nitroscan» (Plant «Promautomatika», Ekaterinburg, Russia) on the basis of non-woven dry wipe and spunlace non-woven fabric with various quantities of the most sensitive fluorophore have been fabricated. The reusable, reversible and sensitive response of the designed prototypes to NACs enables one to qualify these compounds as promising fluorescent sensory materials for detection of NACs. [ABSTRACT FROM AUTHOR]

A number of D–π–A type dyes on the basis of new 2 H -[1,2,3]triazolo[4,5- e ][1,2,4]triazolo[1,5- a ]pyrimidines, bearing various electron-donating carbazole and triphenylamine fragments, have been studied as sensing fluorophores. Fluorescence studies have demonstrated that emission spectra of these compounds in acetonitrile are sensitive to the presence of nitroaromatic explosives, such as 2,4-dinitroanisole (DNAN), picric acid (PA), styphnic acid (SA), 1,3,5-triethoxy-2,4,6-trinitrobenzene (TETNB), 2,4-dinitrotoluene (DNT), 2,4,6-trinitrotoluene (TNT) and nitrobenzene (NB). Detection limits of fluorophores for DNAN, PA, SA, TETNB, DNT and TNT proved to be in the range from 4.82×10 −1 to 2.96×10 −3 mol/L, 2.10×10 −3 to 5.98×10 −5 mol/L, 1.26×10 −1 to 2.02×10 −4 mol/L, 1.58×10 −1 to 1.62×10 −3 mol/L, 1.26×10 −1 to 5.61×10 −4 mol/L and 9.01×10 −2 to 2.77×10 −3 mol/L, respectively. Selective fluorescence quenching response, including a sharp color change under UV irradiation (especially for PA, SA and DNT), makes these compounds promising fluorescence chemosensors for nitroaromatic explosives. [ABSTRACT FROM AUTHOR]

A facile synthetic approach to 5-arylamino-4-(5-nitrofuran- 2-yl)pyrimidines by the Buchwald–Hartwig cross-coupling with various anilines has been developed. All synthesized compounds demonstrated a significant level of in vitro antibacterial activity against Neisseria gonorrhoeae, Streptococcus pyogene and Staphylococcus aureus, including their drug-resistant strains, which is much higher than that of the commercial drug Spectinomycin. [ABSTRACT FROM AUTHOR]

A novel synthetic route to novel thienoacene systems bearing a fused pyrimidine ring is proposed. The commercially available 5-bromopyrimidine is used as the starting material to obtain various dithienoquinazoline and benzo[f]thieno[3,2-h]quinazoline systems through the Suzuki cross-coupling, nucleophilic aromatic substitution of hydrogen (the SNH reaction), and finally palladiumcatalyzed intramolecular cyclization under microwave irradiation. Redox properties of some of the new compounds have been investigated. The data obtained show that these systems have plausible potential for use in organic electronic applications. [ABSTRACT FROM AUTHOR]

The behavior of 4-thienyl substituted pyrimidine ligands (L 1–3 ) has been studied for the series of their reactions with various salts of 3d metals (Co, Zn, Ni, Cu) and platinoids (Pt, Pd). In particular, mononuclear Co(OTf) 2 (L 1–3 ) 2 (H 2 O) 2 (MeCN) 2 ( 1 ), binuclear Co 2 (Piv) 2 (L 1–3 ) 4 ( 2a , b ), Cu 2 (Piv) 2 (L 1–3 ) 2 ( 5a , b ), heterometallic polynuclear Li 2 Co 2 (Piv) 6 (L 1–3 ) 2 ( 4 ) and chelate [(L 1 )Pd(OAc)] 2 ( 6 ) complexes have been obtained. The structures of all complexes have been established by X-ray diffraction. Also magnetic properties of coordination compounds 1 , 2 , 4 and 5 have been studied in details. In particular, mononuclear Co(II) complexes 1 and 4 proved to exhibit paramagnetism with large positive zero-field splitting parameters. Dinuclear Co(II) complexes 2a , b show weak antiferromagnetic interactions. Dinuclear Cu(II) complexes 5a , b demonstrate strong antiferromagnetic superexchange interactions via four carboxylate bridges. The systems 2a , b and 5a , b are isolated as exchange coupled dimers. [ABSTRACT FROM AUTHOR]

Abstract: Six novel donor–π–acceptor organic dyes bearing a pyrimidine as the anchoring group have been obtained in good yields by combination of the microwave-assisted Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen reactions. Their absorption, photoluminescence and electrochemical properties were fully investigated in detail. The infrared spectra of dyes adsorbed on TiO2 indicate the formation of coordinate bonds between the pyrimidine ring of dyes and the Lewis acid sites (exposed Ti n+ cations) of the TiO2 surface. This work demonstrates that the pyrimidine rings of dye sensitizers that form a coordinate bond with the Lewis acid site of a TiO2 surface are promising candidates as the electron-withdrawing anchoring group. The data from quantum calculations show that all of the dyes are potentially good photosensitizers for dye-sensitized solar cells. [Copyright &y& Elsevier]

Abstract: 5-Bromopyrimidine reacts with 2,2′-bithiophene, [2,2′:5′,2″]terthiophene and 2-phenylthiophene in the presence of a palladium catalyst to give 5-(het)aryl substituted pyrimidines due to the palladium-catalyzed aryl–aryl C–C coupling. However 5-bromo-4-(het)aryl-pyrimidines have been prepared from the same starting materials through the SN H-reaction catalyzed by a Lewis acid. Conditions for both types of reactions were optimized. All components of the reaction mixtures, including by-products, have been elucidated by gas–liquid chromatography/mass-spectrometry. Evidence for the structure of 4- and 5-bithiophenyl-substituted pyrimidines has first been obtained by means of X-ray crystallography analysis. Molecular orbital calculations (TDDFT), as well as the redox and optical measurements for all new compounds have also been performed. [Copyright &y& Elsevier]

Abstract: It has been shown that combination of the Suzuki–Miyaura cross-coupling and nucleophilic aromatic substitution of hydrogen is a versatile method for the synthesis of 4-(thiophen-2-yl)-, 5-(thiophen-2-yl)-, and 4,5-di(thiophen-2-yl) substituted pyrimidines from the commercially available 5-bromopyrimidine. The (AE)- and (AO)-reactions of 5-bromopyrimidine with thiophene and 2-bromothiophene have been studied by gas–liquid chromatography/mass-spectrometry. The structures of intermediate σH-adducts, as well as thiophene-(thiophenyl)pyrimidine and bithiophene-(thiophenyl)pyrimidine dyads have first been established by X-ray crystallography analysis. [Copyright &y& Elsevier]

[Display omitted] • A 1,3/1,4-diazine's modified SPE for NB determination in honey was prepared. • Cathodic currents of NB reduction enhanced the diazine-modified SPEs. • The best NB response was obtained by using co-polymerization of the receptor layer. • The low detection limit 0.107 μM allows NB in honey samples to be detected. • The analysis of spiked probes showed the high precision of the sensor with HPLC. In this work, a screen-printed electrode (SPE) modified by 1,3/1,4-diazines was prepared for the rapid and sensitive determination of nitrobenzene (NB). The obtained results indicated enhanced cathodic currents of direct NB reduction into hydroxylaminophenol on the diazine-modified SPEs. The enhanced effect was most likely due to the combination of complexation and collisional processes of diazines towards nitroaromatic compounds and also the diazine-modified electrodes' increased electroconductivity. The best electrochemical responses were obtained in square wave voltammetry mode by using the carbazolyl substituted diazines as a component of the sensitive layer, which was assembled by co-electropolymerization with the unsubstituted carbazole on the electrode during 5 cycles. The low detection limit estimated as 0.107 μM and wide linear range (1–1000 µM) enables NB in water and food samples to be determined. The developed modified electrode was applied in the analysis of commercial honey samples. [ABSTRACT FROM AUTHOR]

• 1,3-Diazine-based D–(π)– D–(π)–A emitters were synthesized and investigated. • Non-doped OLEDs achieved maximum current efficiency up to 1.8 cd/A. • Green-Yellow OLEDs demonstrating maximum brightness up to 1.4 × 104 cd/m2. • Protonated pyrimidinium salts are perspective laser dyes. Two novel V-shaped push-pull systems based on a pyrimidine acceptor have been designed and investigated. Low-temperature measurements of the fluorescence and delayed luminescence spectra demonstrated that the emission bands of the compounds have a charge-transfer character. Despite the fact that compounds in thermal vacuum deposition films have a low fluorescence quantum yield, OLED devices based on them show high efficiency, which can be associated with the emission mechanism through delayed fluorescence. It is found that photoproducts, obtaining upon exposure to UV-irradiation of fluorophores in chloroform solution, exhibit laser activity in the red region of the spectrum. [ABSTRACT FROM AUTHOR]

Highly sensitive and selective detection of nitro containing high energy organic compounds such as picric acid (PA), 2,4,6-trinitrotoluene (TNT) and 2,4-dinitrotoluene (DNT) has become a challenging task due to concerns over national security, criminal investigations and environment protections. Among various known detection methods, fluorescence sensors have gained special attention in recent time. The family of fluorescent sensors based on push-pull systems that incorporate nitrogen heterocycles as an electron-withdrawing group have a growing interest due to their high sensitivity, selectivity and easy tuning. The fluorescent sensors discussed in this review are classified and organized according to used azaheterocyclic scaffold, their functionality and their ability to detect of nitroaromatics by fluorescence quenching. Image 1 • Analyze the design of turn-off sensors towards nitroaromatic compound based on azaheterocyclic push-pull fluorophores. • Discuss the detection mechanisms of nitroaromatic compounds by fluorescent probes. • Provide valuable suggestions on sensor design for the developing trend of high effective sensors towards nitroexplosives. [ABSTRACT FROM AUTHOR]