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A convenient and efficient approach toward the synthesis of seven aromatically substituted xanthendiones 1‒7 and one structurally-related xanthenone 8 through condensation of dimedone and the appropriate aromatic aldehyde is reported. Further, their chemical structure was confirmed by melting points, elemental analysis, FT-IR, 1H-, 13C-NMR and UV–Vis spectroscopic methods. The relationship between the chemical structure and pharmacological activity was determined empirically using appropriate software packages and in vitro using the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) method. The results of in silico prediction suggested that all investigated compounds possess good oral bioavailability. The results of the ABTS assay indicate that five compounds possess the ability to scavenge the ABTS•+ radical cation. Based on the comparison of the IC50 values, the activity of the compounds was found to be as follows: 6 > 1 > 7 > 2 > 8. The effects of solvent dipolarity/ polarizability and solute solvent–hydrogen-bonding interactions on the shifts of the absorption maxima were rationalized by means of the linear solvation energy relationship concepts proposed by Kamlet–Taft and Catalán.

Spirohidantoins represent an pharmacologically important class of heterocycles since many derivatives have been recognized that display interesting activities against a wide range of biological targets. First synthesis of cycloalkanespiro-5-hydantoins was performed by Bucherer and Lieb 1934 by the reaction of cycloalkanone, potassium cyanide and ammonium-carbonate at reflux in a mixture of ethanol and water. QSAR (Quantitative Structure-Activity Relationship) studies showed that a wide range of biological activities of spirohydantoin derivatives strongly depend upon their structure. This paper describes different methods of synthesis of spirohydantoin derivatives, their physico-chemical properties and biological activity. It emphasizes the importance of cycloalkanespiro-5-hydantoins with anticonvulsant, antiproliferative, antipsychotic, antimicrobial and antiinflammatory properties as well as their importance in the treatment of diabetes. Numerous spirohydantoin compounds exhibit physiological activity such as serotonin and fibrinogen antagonist, inhibitors of the glycine binding site of the NMDA receptor also, antagonist of leukocyte cell adhesion, acting as allosteric inhibitors of the protein-protein interactions. Some spirohydantoin derivatives have been identified as antitumor agents. Their activity depends on the substituent presented at position N-3 of the hydantoin ring and increases in order alkene > ester > ether. Besides that, compounds that contain two electron withdrawing groups (e.g. fluorine or chlorine) on the third and fourth position of the phenyl ring are better antitumor agents than compounds with a single electron withdrawing group. [Projekat Ministarstva nauke Republike Srbije, br. 172013]

To obtain an insight into the interactions of potential anticonvulsant drugs with their surrounding, two series of 5-methyl-5-aryl- and 5-ethyl-5-arylhydantoins were synthesized and their absorption spectra were recorded in the region from 200 to 400 nm in a set of selected solvents. The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding interactions on the absorption maxima shifts were analyzed by means of the linear solvation energy relationship (LSER) concept of Kamlet and Taft. The ratio of the contributions of specific and nonspecific solvent-solute interactions were correlated with the corresponding ADME properties of the studied compounds. The correlation equations were combined with different physicochemical parameters to generate new equations, which demonstrate the reasonable relationships between solvent-solute interactions and the structure-activity parameters. [Projekat Ministarstva nauke Republike Srbije, br. 172013]

Oxaprozin (3-(4,5-difeniloksazol-2-yl)propanoic acid) is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of numerous inflammatory musculoskeletal diseases, including rheumatoid arthritis, osteoarthritis, tendonitis, ankylosing spondylitis and bursitis. It is the first representative member of the diaryl-substituted heterocyclic compounds, which have found clinical use as selective cyclooxygenase-2 (COX-2) inhibitors. U.S. Food and Drug Administration (FDA) approved its official use in 1992. Both anti-inflammatory and analgesic properties of oxaprozin are mainly due to the potent inhibition of COX. However, oxaprozin-induced benefits might be also regulated by other COX-independent pathways. It has been shown that oxaprozin induced direct proapoptotic effects in CD40L-treated human monocytes independently of COX inhibition. It also has several advantages in the treatment of inflammatory diseases in comparison to other NSAIDs such as aspirin, naproxen, indomethacin and phenylbutazone, which enabled oxaprozin to become one of the most used NSAIDs in America. Oxaprozin, as other members of the group of NSAIDs, can cause gastrointestinal complications, but significantly lower due to relatively high pKa value. In this paper, importance of oxaprozin in the treatment of arthritis and its pharmacokinetic properties were described, therewith its activity and side effects were compared with other commercially available anti-inflammatory drugs.

Over 50% of all colorants which are used nowdays are azo dyes and pigments, and among them arylazo pyridone dyes (and pigments) have became of interest in last several decades due to the high molar extinction coefficient, and the medium to high light and wet fastness properties. They find application generally as disperse dyes. The importance of disperse dyes increased in the 1970s and 1980s due to the use of polyester and nylon as the main synthetic fibers. Also, disperse dyes were used rapidly since 1970 in inks for the heat-transfer printing of polyester. The main synthetic route for the preparation of azo dyes is coupling reaction between an aromatic diazo compound and a coupling component. Of all dyes manufactured, about 60% are produced by this reaction. Arylazo pyridone dyes can be prepared from pyridone moiety as a coupling component, where substituent can be on nitrogen, and diazonim salts which can be derived from different substituted anilines or other heterocyclic derivatives. In addition, arylazo dyes containing pyridone ring can be prepared from arylazo diketones or arylazo ketoesters (obtained by coupling β-diketones or β-ketoesters with diazonim salts) by condensation with cyanoacetamide. Disazo dyes can be prepared by tetrazotizing a dianiline and coupling it with a pyridone or by diazotizing aniline and coupling it with a dipyridone. Trisazo dyes can be also prepared by diazotizing of aniline and coupling it with a tripyridone or by hexazotizing a trianiline and coupling it with a pyridone. The main goal of this paper is to give a brief review on the synthesis of arylazo pyridone dyes due to the lack of such reviews. In addition, some properties of arylazo pyridone dyes as light fastness and azo-hydrazon tautomerism are disccused.

This paper is concerned on the development of the optimal laboratory procedure for the synthesis of calcium lactate pentahydrate and the application of obtained results in a project for a semi-industrial installation for its production. Calcium lactate is used as an additive in numerous food and pharmaceutical products. Basically, it has to satisfy quality requirements. That was the reason why the procedure for its synthesis had to be optimized in aspects of selection of reactants, their molar ratio, necessary laboratory equipment, reactant addition order, working temperature, isolation of final product from the reaction mixture, yield and product quality. A semi-industrial installation for the production of calcium lactate pentahydrate is projected on the basis of the results of this investigation. The importance of this investigation arises from the fact that this salt is not produced in Serbia and the complete quantity (about 20 t per year) is imported.

Several 5-methyl-5-(3- or 4-substituted phenyl)hydantoins were prepared and their ultraviolet absorption spectra were recorded in the region 200-400 nm in twelve solvents of different polarity. The effect of solvent dipolarity/ polarizability and solvent/solute hydrogen bonding interactions were analyzed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The lipophilic activity of the investigated hydantoins was estimated by calculation of log P values with Advanced Chemistry Development Software. The calculated values of log P were correlated with the contribution of hydrogen bond donor-solvent interactions. By employing the thus obtained linear dependence, the pharmacological activity of the studied hydantoin derivatives is discussed.

The aim of this investigation is the development of the optimal laboratory procedure for the synthesis of calcium and sodium citrate and the application of obtained results in a project for a semi-industrial installation for its production. These salts are used as an additive in numerous food and pharmaceutical products. Basically, they have to satisfy quality requirements, which is the reason why the procedure for their synthesis needs to be optimized in aspects of selection of reactants, their molar ratio, necessary laboratory equipment, reactant addition order, working temperature, isolation of final product from the reaction mixture, yield and product quality. A semi-industrial installation for the production of calcium and sodium citrate will be projected on the basis of the results of this investigation. The importance of this investigation is the fact that these salts are not produced in our country and the entire quantity (about 20 t per year) is imported.

The 13C- and 1H-NMR chemical shifts of thirteen N(1)-(4-substituted phenyl)-3-cyano-4,6-dimethyl-2-pyridones were measured in deuterated dimethyl sulfoxide (DMSO-d6). The correlation analysis for the substituent-induced chemical shifts (SCS) with σp, inductive (σI) and different scale of resonance (σR) parameters were performed using the SSP (single substituent parameter), DSP (dual substituent parameter) and DSP-NLR (dual substituent parameter-non-linear resonance) methods. The results of the calculations concerning the polar and resonance effects satisfactorily describe the substituent effects at the carbon atoms of interest. The mode of transmission of the substituent effects, both inductive and resonance, in relation to the geometry of the investigated pyridones is discussed.

The principle of linear free energy relationships was applied to the 1H chemical shifts of the β-vinyl proton atoms of 3-methylene-2-substituted-1,4-pentadienes. The correlations of the proton chemical shifts with Swain and Lupton substituent parameters provide a mutually consistent picture of the electronic effects in these compounds. The overall pattern of proton chemical shifts can be largely accounted for by a model of substituent effects based on field, resonance and ¶ polarization effects. Owing to the particular geometric arrangement of the vinyl group in 3-methylene-2-substituted-1,4-pentadienes, the β-vinyl protons HB and HC have different sensitivities to polar and resonance effects. The different sensitivities of the 1H chemical shifts to resonance effects reveals some effects not predicted by the model outlined above. Evidence is presented that demonstrates that both the 1H and 13C chemical shifts for these compounds reflect their ground-state charge densities.

The principles of linear free energy relationships were applied to the 13C substituent chemical shifts (SCS) of the carbon atoms in the unsaturated chain of 3-methylene-4-substituted-1,4-pentadienes. Correlations of the SCS with the substituent parameters of Swain and Lupton provide a mutually consistent picture of the electronic effects in these compounds. The pattern of the electronic effects can be fully rationalized by a model based on the direct transmission of substituent effects through-space (direct through-space field effects), and via conjugative interactions (resonance effects), or by substituent-induced polarization of the ¶-system in the unsaturated chain (¶-polarization effect). Semi-empirical MNDO-PM3 calculations suggest the s-cis conformation of 3-methylene-4-substituted-1,4-pentadienes as the one with minimal heat of formation.

A number of 5-substituted-4-methyl-3-cyano-6-hydroxy-2-pyridones from cyanoacetamide and the corresponding alkyl ethyl acetoacetates were synthesized according to modified literature procedures. The alkyl ethyl acetoacetates were obtained by the reaction of C-alkylation of ethyl acetoacetate. An investigation of the reaction conditions for the synthesis of 4-methyl-3-cyano-6-hydroxy-2-pyridone from cyanoacetamide and ethyl acetoacetate in eight different solvents was also performed. The ultraviolet absorption spectra of synthesized pyridones were measured in nine different solvents in the range 200-400 nm. The effects of solvent polarity and hydrogen bonding on the absorption spectra are interpreted by means of linear solvation energy relationships using a general equation of the form v = vo + sπ*+aα+bβ, where π* is a measure of the solvent polarity, α is the scale of the solvent hydrogen bond donor acidities and β is the scale of the solvent hydrogen bond acceptor basicities.

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In this paper, spectroscopic and quantum mechanical investigation of nine 4-aryl-5-arylazo-3-cyano-6-hydroxy-2-pyridone dyes was performed, and obtained density functional theory ( DFT) results were compared with experimental data. The structural and spectroscopic properties of azo-2-pyridone dyes were studied by DFT using B3 LYP, CAM-B3 LYP, and M06-2X methods with a 6-311++G(d,p) basis set. Comparison of results reveals that the scaled theoretical vibrational frequencies of azo dyes are in good agreement with experimental data. The time-dependent DFT calculated and experimental ultraviolet-visible ( UV-vis) absorption spectra are also in good agreement. The effect of electron-donating - OCH3 and electron-withdrawing - NO2 groups on the structural parameters, vibrational frequencies, UV-vis absorption, and natural bond orbital ( NBO) atomic charges were thoroughly analysed. Vibrational, UV-vis, and NBO analyses confirm that investigated dyes exist in the hydrazo tautomeric form in the solid state and ethanol solution. These analyses signify the occurrence of intramolecular charge transfer in these azo-pyridone dyes. [ABSTRACT FROM AUTHOR]

Copyright of Chemical Industry / Hemijska Industrija is the property of Association of Chemical Engineers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The 13C NMR chemical shifts of the C2 carbon atom in the heteroaromatic nuclei of seventeen 5-(3- and 4-substituted arylazo)-4,6-dimethyl-3-cyano-2-pyridones were determined in deuterated DMSO solution. For quantitative assessment of the substituent effects on the 13C NMR chemical shifts simple and extended Hammett equations and Swain-Lupton equation were used. The mode of transmission of substituent effects have been discussed in a relation to the geometry of investigated molecules. The geometry data were obtained using semiempirical MNDO-PM6 energy calculations. The observed 13C NMR substituent chemical shifts were correlated with literature 13C NMR data for the corresponding 3- and 4-substituted-2′,6′-dimethylazobenzenes and 3- and 4-substituted azobenzenes. A good linear dependence obtained in this way, provided a basis to discuss the influence of the ortho-methyl groups on the degree of coplanarity of azobenzene and pyridone systems, and on the efficiency of transmission of electronic substituent effect from one ring to the other one. [ABSTRACT FROM AUTHOR]

A series of some new pyridone arylazo dyes was synthesized from the corresponding diazonium salts and 4,6-diphenyl-3-cyano-2- pyridone using the classical reaction for the synthesis of the azo compounds. The structures of these dyes were confirmed by UV-vis, FTIR and 1H-NMR spectroscopic techniques. The solvatochromism of the dyes was evaluated with respect to visible absorption properties in various solvents. The effects of solvent dipolarity/polarizability and solvent/solute hydrogen bonding interactions were analyzed by means of the linear solvation energy relationship concept proposed by Kamlet and Taft. The 2-pyridone/2-hydroxypiridine tautomeric equilibration was found to depend on the substituents as well as on the solvents. [ABSTRACT FROM AUTHOR]