Presence Of Potassium Carbonate Research Articles

In-silico Studies, Design, and Synthesis of Pyrimidine-linked Benzothiazoles for its Anticonvulsant Potential.

The objective of the study was to design and synthesize a series of N-(6-substituted-1,3-benzothiazole- 2-yl)-2-{[6-(3-substitutedphenyl)-5-cyano-2-sulfanylpyrimidine-4-yl)]amino}acetamide derivatives BPD (1-15) that contains key pharmacophores required for anticonvulsant action. The titled compounds (BPD 1-15) were synthesized by reacting 2-substituted-N-(6-chlorobenzo[d]thiazol2-yl)acetamide with 4-amino-6-(4-substituted phenyl)-2-mercapto pyrimidine 5-carbonitrile in the presence of potassium carbonate and dry acetone. The synthesized compounds BPD (1-15) were assessed in vivo by the maximum electric shock (MES) test and the subcutaneous pentylenetetrazol (scPTZ) test in mice. The neurotoxicity test was performed by the rotarod test. A molecular docking study of title compounds with a sodium channel receptor (PDB ID: 1BYY) was carried out using the SP Docking protocol of the Glide module of the Maestro. Pharmacophore modeling was used to qualitatively identify the chemical characteristics for ligand binding and their spatial configurations in the 3D space of the active site. Among the studied compounds, BPD-15 and BPD-5 compounds showed significant action in both the MES and scPTZ models, with no neurotoxicity. BPD-15 & BPD-5 were relatively safe in acute toxicity testing. Compounds BPD-15 and BPD-5 showed good dock scores of -6.434 and -6.191, respectively. Thus, the compounds BPD-15 and BPD-5 have shown a considerable affinity towards the sodium channel as compared to the standard drug Riluzole. Compound BPD-14 showed good drug compatibility, and compounds BPD-1, BPD-2, BPD-11, BPD-12, BPD-13, BPD-14, BPD-15 showed good ADME values.

New Synthesis of 2-Aminopyrimidines by Amination of Biginelli Reaction Products — Oxadiazocines

Abstract Previously, we synthesized methanobenzo[g][1,3,5]oxadiazocines and methanonaphtho[2,3-g]­[1,3,5]oxadiazocines via the Biginelli reaction using thiourea with acetoacetic ester or acetylacetone and salicylaldehyde or 2-hydroxy-1-naphthaldehyde under acidic catalysis and microwave irradiation. These compounds were then subjected to alkylation reaction with ethyl bromide in the presence of potassium carbonate in dimethylformamide. Under these mild reaction conditions, possible thione-thiol tautomerism of the oxadiazocines, as well as their structural analogs of cyclic thioureas, predominantly yielded in S-alkylation products with minor amounts of N-alkylation products. Further nucleophilic substitution reactions of S-ethyl-methanobenzo[g][1,3,5]oxadiazocines and S-ethyl-methanonaphtho[2,3-g][1,3,5]oxadiazocines revealed that alongside nucleophilic substitution by morpholine, elimination of phenol or naphthol occurred, followed by aromatization of the dihydropyrimidinone ring into an aromatic pyrimidine ring, resulting in the formation of 2-morpholinyl-substituted pyrimidines. Only a few examples and multi-step syntheses for obtaining such 2-amino-substituted pyrimidines are presented in the literature. Therefore, our newly discovered method for obtaining widely demanded derivatives of 2-aminopyrimidines is presented both relevant and promising.

Synthesis of N-heterocyclic carbene gold(I) complexes from the marine betaine 1,3-dimethylimidazolium-4-carboxylate.

The marine natural product norzooanemonin (1,3-dimethylimidazolium-4-carboxylate) has been used to prepare a series of carboxyl- or carboxylate-functionalized N-heterocyclic carbene (NHC) gold(I) complexes from [(Me2S)AuCl] in the presence of potassium carbonate. The potential of the resulting mono- and dicarbene complexes to act as cytotoxic or antibacterial drugs was investigated.

Directional transformation and migration pathways of nitrogen during pig manure supercritical water gasification

Nitrogen is a valuable nutrient element in pig manure. This work focuses on investigating the distribution, directional transformation, and migration pathways to facilitate the recovery of nitrogen from supercritical water gasification products. Results indicated that no nitrogen-containing gas was detected and 12.65 % of nitrogen remained in solid products. 82.49 % of nitrogen migrated into liquid products, which are predominated by ammonia. Catalysts were employed to promote the conversion of solid nitrogen to liquid nitrogen and organic nitrogen to ammonia. Finally, 85 % of nitrogen is enriched into liquid products and ammonia predominated the liquid nitrogen. The percentage of ammonia increased to 97.51 % at 620 °C in the presence of potassium carbonate. The migration pathways indicated that nitrogen was transformed into ammonia by various intermediates such as indole. The rest of the nitrogen remained in solid products with stable quaternary-nitrogen. These findings provide valuable insights into nitrogen management and recovery.

Synthesis and Biological Evaluation of 1-Substituted (R)-6-(2?-Cyano-1?-Pyrrolidin-yl)-4-(3?- Hydroxyadamantan-1?-yl)-3-phenyl-1,2,4-triazines

A series of various 1-substituted (R)-6-(2?-cyano-1?-pyrrolidin-yl)-4-(3?-hydroxy adamantan-1?-yl)-3-phenyl- 1,2,4-triazines (5a-i) was synthesized by the reaction of (R)-6-(2?-cyano-1?-pyrrolidin-yl)-4-(3?-hydroxy adamantan-1?- yl)-3-phenyl-1,4-dihydro-1,2,4-triazine (4) with heterocyclic halogenated compounds (R-X) in the presence of potassium carbonate. All the synthesized compounds were evaluated biologically and also determined In vitro cytotoxicity of compounds 5a, 5c, 5d, 5e, 5g, and 5h against human cervical cancer cell line (HeLa). Among all the synthesized compounds, some compounds exhibited potent antimicrobial activity as well as cytotoxicity.. KEYWORDS :1,2,4-Triazine, Adamantanol, Biological activities, Pyrrolidine.

Microwave Synthesized Hydrophilic 4‐Oxo‐2‐phenylquinazoline‐3(4H)–carboximidamide and –Carboxamide as Privileged Small Molecule Scaffolds with Anti‐HIV‐1 Activities

AbstractOpportunistic infections like tuberculosis (TB) are prevalent in HIV‐infected individuals. In an approach to introducing an industrial‐scale microwave‐assisted production of agents having both antiviral and antibacterial properties, a set of hydrophilic 2,3‐substituted quinazolinones, 4‐oxo‐2‐phenylquinazoline‐3(4H)‐carboximidamide (Qg) and 4‐oxo‐2‐phenylquinazoline‐3(4H)‐carboxamide (Qu), were afforded in encouraging yields. They were obtained by treating 2‐benzamidobenzoyl chloride with guanidine hydrochloride or urea in the presence of potassium carbonate in DMF. DFT calculations were employed for geometrical optimization and vibrational frequency analysis of the compounds. Free energies of solvation (ΔGsol) of Qg, and Qu calculated using DFT lend evidence in support of their hydrophilicity The anti‐HIV‐1 activities of the small‐molecule quinazolinone derivatives Qg and Qu were investigated. The synthons under in vitro conditions inhibit the entry of HIV in receptor cells with low cytotoxicity (EC50=50.53 nM for Qu and EC50=97.92 nM for Qg). The study identifies the antiviral properties of the two benzo‐fused pyrimidine derivatives, which were earlier reported to have antitubercular activity. Our findings indicate the scope for further synthetic explorations of these quinazolinone scaffolds that can lead to developing promising alternatives in drug design, pharmaceutics, and clinical research.

Synthesis of Bis‐Nicotinonitrile Derivatives and Investigations of Antimicrobial and Antibiofilm Activities

AbstractIn this study aimed to the synthesis of novel bis‐nicotinonitrile derivatives starting from 1,3‐bis‐chalcones and investigate their antimicrobial activity potentials. Bis‐nicotinonitrile derivatives were synthesized from 1,3‐bis‐chalcone derivatives reacted with malononitrile in ethanol in the presence of potassium carbonate. Characterization of the obtained compounds was carried out by spectroscopic methods. In total, 12 new 1,3‐phenylene‐bis‐nicotinonitrile derivatives were synthesized. Finally, the antimicrobial and antibiofilm activities of synthesized 1,3‐phenylene‐bis‐nicotinonitrile derivatives were tested against 5 microorganisms. As a result, it was observed that the synthesized new nicotinonitrile derivatives were quite active especially in terms of antibiofilm activity.

Enhanced LC-ESI-MS/MS Sensitivity by Cationic Derivatization of Organophosphorus Acids.

The chemical derivatization to enhance the signal intensity and signal-to-noise (S/N) of several organophosphorus (OP) acids in liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS) is illustrated. The OP class of compounds represents the environmental degradants of OP nerve agents and pesticides. N-(2-(bromomethyl)benzyl)-N,N-diethylethanaminium bromide (CAX-B) was utilized to derivatize a panel of eight acids consisting of five alkyl methylphosphonic acids (ethyl-, isopropyl-, isobutyl-, cyclohexyl-, and pinacolyl-methylphosphonic acid) along with three dialkylphosphate analogs (diethyl-, dibutyl-, and diethyl thio-phosphate). The derivatization reaction with CAX-B was conducted in acetonitrile in the presence of potassium carbonate at 70 °C for 1 h. The resulting acid derivatives were analyzed with an LC-Orbitrap-ESI-MS/MS, and their dissociation processes were investigated. It was found that the derivatization procedure increased the limits of identification (LOIs) by one to over two orders of magnitude from the range of 1 to 10 ng/mL for the intact OP-acids to the range of 0.02-0.2 ng/mL for the derivatized acids utilizing an LC-MS(QqQ) in MRM mode, regardless of the sample matrix (hair, concrete, or plant extracts). The interpretation of the corresponding ESI-MS/MS spectra for each type of derivatized sub-OP family revealed the formation of characteristic neutral losses and a characteristic ion for the organophosphorus core. This derivatization is beneficial and useful for screening and identifying target and "unknown" OP acids.

Synthesis of 4-(Phenylchalcogenyl)tetrazolo[1,5-a]quinolines by Bicyclization of 2-Azidobenzaldehydes with Phenylchalcogenylacetonitrile.

A general methodology to access valuable 4-(phenylchalcogenyl)tetrazolo[1,5-a]quinolines was developed by the reaction of 2-azidobenzaldehyde with phenylchalcogenylacetonitriles (sulfur and selenium) in the presence of potassium carbonate (20 mol%) as a catalyst. The reactions were conducted using a mixture of dimethylsulfoxide and water (7:3) as solvent at 80 °C for 4 h. This new methodology presents a good functional group tolerance to electron-deficient and electron-rich substituents, affording a total of twelve different 4-(phenylchalcogenyl)tetrazolo[1,5-a]quinolines selectively in moderate to excellent yields. The structure of the synthesized 4-(phenylselanyl)tetrazolo[1,5-a]quinoline was confirmed by X-ray analysis.

Syntheses, crystal structures and Hirshfeld surface analysis of 2-(benzyl-sulfan-yl)-5-[4-(di-methyl-amino)-phen-yl]-1,3,4-oxa-diazole and 2-[(2-chloro-6-fluoro-benz-yl)sulfan-yl]-5-[4-(di-methyl-amino)-phen-yl]-1,3,4-oxa-diazole.

The title compounds were synthesized by alkyl-ation of 5-[(4-di-methyl-amino)-phen-yl]-1,3,4-oxa-diazole-2-thiol with benzyl chloride or 2-chloro-6-fluoro-benzyl chloride in the presence of potassium carbonate. The yields of 2-(benzyl-sulfan-yl)-5-[4-(di-methyl-amino)-phen-yl]-1,3,4-oxa-diazole, C17H17N3OS (I), and 2-[(2-chloro-6-fluoro-benz-yl)sulfan-yl]-5-[4-(di-methyl-amino)-phen-yl]-1,3,4-oxa-diazole, C17H15ClFN3OS (II), were 96 and 92%, respectively. In the crystal structures of (I) and (II), C-H⋯π inter-actions are observed between neighboring mol-ecules. Hirshfeld surface analysis indicates that H⋯H and H⋯C/C⋯H inter-actions make the most important contributions to the crystal packing.

Synthesis, Antibacterial, and Antifungal Evaluation of Some New Quinazolinone-Azole Hybrids

Nowadays, the need to replace the existing drugs is felt more than ever by increasing drug resistance. Quinazoline is one of the major heterocyclic compounds in biological activity. This research was done to synthesize new derivatives of quinazolin-4(3H)-one and evaluation of their antibacterial and antifungal properties. Ten new quinazolin-4(3H)-one derivatives (5(a–d), 6(a–d), and 7(a,b)) were synthesized by using the nucleophilic substitution reaction of 2-(chloromethyl)-3-(4-chlorophenyl) quinazolin-4(3H)-one (4) and the heterocyclic moieties of 1,3,4-oxadiazole I(a–d) or 1,2,4-triazole (II(a–d), III(a,b)) in the presence of potassium carbonate as base and in acetone as solvent. The chemical structures of the products were approved using 1H-NMR, 13 C-NMR, IR, and Mass spectroscopy. The antimicrobial activity of the compounds was assessed against a panel of Gram-positive and Gram-negative bacteria and species of Candida and Aspergillus fungal. Minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC), and inhibition zone (IZ) of these compounds were determined. As results shown, 7a showed better effects against Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa than the other compounds. However, 5d showed better effects against Proteus vulgaris. Compound 6b showed better effects against Candida albicans, Aspergillus fumigatus, and Aspergillus niger, also compound 5a showed better effects against Candida glabrata.

2-(3-Bromophenyl)imidazo[2,1-b]oxazole

The microwave-assisted reaction of 2-nitroimidazole with 3-bromophenacyl bromide in the presence of potassium carbonate as a base and dimethylformamide as a solvent afforded 2-(3-bromophenyl)imidazo[2,1-b]oxazole. The formation of this compound was explained via a domino mechanism comprising an initial N-alkylation reaction of the imidazole substrate, followed by the base-promoted deprotonation of the position adjacent to the carbonyl to give an enolate anion that finally cyclizes via an intramolecular SNAr reaction, with the loss of the nitro group as potassium nitrite. Then, the proposed 1-(3-bromophenacyl)-2-nitroimidazole intermediate could be isolated by reducing the reaction time and was shown to be a precursor of the imidazo[2,1-b]oxazole final product.

Microwave-assisted Synthesis of 3-amino-2-phenylquinazolin-4(3H)-one (QH) and 4-oxo-2-phenylquinazoline-3(4H)-carbothioamide (QTh)

Background: Microwave synthesis has developed as a powerful tool for the cost-effective and greener synthesis of organic molecules, including quinazolines. Irradiation with microwave leads to the excitation of molecules and equitable distribution of thermal energy in a much shorter time than conventional synthesis. This results in shorter reaction time and, more often than not, higher efficiency Objective: The primary objective of the work presented in this article was to prepare hydrazine hydrate or thiourea derivative of quinazolines through microwave synthesis as small-molecule scaffolds for fur-ther need-based functionalisation, isolation, and characterisation. We, herein, report the synthesis of two quinazolinone derivatives of thiourea and hydrazine, 3-amino-2-phenylquinazolin-4(3H)-one (QH) and 4-oxo-2-phenylquinazoline-3(4H)-carbothioamide (QTh), respectively. Method: A multi-step synthetic strategy starting from anthranilic acid was employed to synthesise the small molecule quinazolinones 3-amino-2-phenylquinazolin-4(3H)-one (QH) and 4-oxo-2-phenylquinazoline-3(4H)-carbothioamide (QTh). The compounds were synthesised by reacting hydra-zine and thiourea with 2-benzamidobenzoyl chloride in DMF under microwave irradiation (800 W at 135 °C for 4 min) in the presence of potassium carbonate. The acid chloride was prepared by chlorination of 2-benzamidobenzoic acid, which in turn was synthesised from anthranilic acid by benzoylation. This method is an efficient alternative approach to synthesising quinazolinones from benzoxazin-4-ones. Results: We have successfully synthesised, isolated, and characterised the quinazolinone derivative QH (yield: 81%) and QTh (yield: 85%). The structures of the compounds were established through spectro-scopic techniques. Theoretical optimisation of the structures was also achieved using DFT. The HOMO-LUMO difference for QH and QTh was calculated to be 4.60 and 4.47 eV, respectively. Conclusion: The reported protocol is advantageous over conventional methods of quinazoline synthesis from benzoxazin-4-ones. The time required for the reaction is much less (4 min) as compared to the usual requirements of reflux (> 4 h); the higher energy gap of QH indicates greater stability than that of QTh.

A novel, swift, and effective green synthesis of morpholino-pyridine analogues in microwave irradiation conditions

We report a facile, efficient, and environmentally benign approach for preparing morpholino-linked 1,4-dihydropyridine derivatives. The four-component fusion of morpholin-4-amine, diethyl acetylene dicarboxylate, malononitrile, and chosen substituted benzaldehydes occurred under microwave irradiation under mild conditions in the presence of potassium carbonate as a catalyst. This protocol offers remarkable benefits such as excellent yields (92–98 %), easy handling, simple workup, economy, cleaner reaction profile, green conditions, shorter reaction time (≤10 min), and avoiding column chromatography for purification.

Search for fungistatics in the imidazole series

New imidazole derivatives with fungistatic activity were synthesized at the NCRSRVI branch of FSBSC Federal Rostov Agrarian Scientific Center. The initial compound 4,5-dichlorimidazole was obtained according to the method described in the literature [3]. Structures 1, 4, 6, 7, 8 - 11, 14 - 17, 19, 20, 22, 24 they were synthesized by alkylation of 4,5-dichlorimidazole with corresponding halide alkyls in an alkaline medium. Alcohol 5 was obtained by reducing ketone with sodium borohydride in ethanol. Bigeterocycles 10, 13 were obtained by the reaction of 4,5-dichlorimidazole with corresponding chloronitropyridines by boiling in dimethylformamide in the presence of potassium carbonate. Compound 10 was obtained under similar conditions, but ortho-chloronitrobenzene was used as an aryl derivative. The preparation 23 was obtained by acylation using a chlorocarbon ester of the corresponding N-(4-aminophenylmethyl) 4,5-dichlorimidazole, which, in turn, was synthesized from a nitro derivative by reduction with iron in ethanol in the presence of a catalytic amount of hydrochloric acid. Preparation 18 is obtained from the methyl ester of 4,5-dichlorimidazole and acetic acid and hydrazine in an alcoholic medium. The study of fungistatic activity showed that the size of the culture growth retardation zone crucially depends on the type of substituents in the nitrogen atom of the imidazole cycle. First of all, this applies to the lipophilicity of the substituent: the higher the lipophilicity (of the compound 1, 4, 6, 7, 20, 22-24), the higher the activity of the connection. However, lipophilicity obviously should not exceed certain limits: the most lipophilic compounds 2 and 3 are significantly inferior in activity to slightly less lipophilic compounds 1, 4, 6, 7, 20, 22-24. Polar substituents of the nitrogen atom (compounds 5, 8, 11, 16-18, 23) completely suppress fungistatic activity. The aryl substituent of the nitrogen atom of the imidazole ring (compound 10), as well as the nitrogetaryl substituents (compounds 12 and 13) have significant fungistatic activity.

Synthesis and effect of N-alkylation on antibacterial activity of 2-(Benzylthio) methyl-1H-benzimidazole derivatives

In pursuit the development of novel potent and selective antibacterial agents, we synthesized twelve (12) N-alkyl 2-benzylthiomethyl-1H-benzimidazole derivatives and evaluated their antibacterial activities. Their antibacterial profile was determined with minimal inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) against a small set of two (2) strains Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive). These compounds are produced by the condensation reaction of 2-benzylthiomethyl-1H-benzimidazole (5) with benzyl chloride or bromide (6) in the presence of potassium carbonate (K2CO3). The panel of twelve synthetized compounds (7a-l) were characterized by NMR 1H, 13C spectroscopy, and high-resolution mass spectrometry (HRMS). The results showed that compounds 7a, 7b, 7c, 7d, 7e, 7f, 7h, 7k, and 7l were potent against Escherichia coli and Staphylococcus aureus, with significant MICs values from 140 to 290 µg/mL. On E. coli, five (5) compounds 7b, 7f, 7i, 7k and 7l showed bactericidal effects within common an N-alkylation by R3= phenyl, methyl, and CH2OH on the benzimidazole scaffold and the benzylthiol substituted by R2= Cl or CF3. This is evidence or a probe of these chemical groups implementing the bactericidal activity.

N-(9,10-Dioxo-9,10-dihydroanthracen-1(2)-yl)-2-(R-thio) Acetamides: Synthesis, Antioxidant and Antiplatelet Activity.

The synthesis of new N-(9,10-dioxo-9,10-dihydroanthracen-1(2)-yl)-2-(R-thio) acetamides was carried out using reaction of 2-chloro-N-(9,10-dioxo-9,10-dihydroanthracene-1(2)-yl)acetamides with functionalized thiols in the presence of potassium carbonate in N,N-dimethylformamide (DMF) at room temperature. Evaluation of the synthesized compounds on such indicators of radical scavenging activity as lipid peroxidation (LP) and oxidative modification of proteins (OMP) in vitro in rat liver homogenate was carried out. It was determined that the compounds with a substituent in the first position of anthracedione core showed better antioxidant properties than their isomers with a substituent in the second position. The compounds 6 and 7 with the best indicators of radical-scavenging activity were determined. Antioxidant effect in OMP processes was also determined for compound10. The antiplatelet activity study in vitro revealed compound 10 with the inhibited effect of ADP-induced aggregation.

Synthesis of 5-membered Heteroaryl-substituted Benzyloxy-benzaldehydes by the Suzuki-Miyaura Coupling Reaction

Abstract: In medicinal chemistry, benzyloxy-benzaldehyde is a valuable intermediate, to which the attachment of a five membered heterocycle may be advantageous from the point of view of drug design. The starting iodo-benzyloxy-benzaldehydes were synthesized by the O-benzylation of o-, m- and p-hydroxybenzaldehydes with 2-, 3- and 4-iodobenzylbromides in refluxing acetone or acetonitrile in the presence of potassium carbonate and potassium iodide. Starting from the corresponding iodo-benzyloxy-benzaldehydes, the Suzuki-Miyaura carbon-carbon cross-coupling reaction was utilized to get five membered heteroaryl-substituted benzyloxy-benzaldehydes. Various methods for Suzuki cross-coupling were studied. The applied boronic acids were 2- and 3-thiophene-boronic acids, as well as 2- and 3-furan-boronic acids. The reactions were followed by TLC and HPLC-UV-MS analysis. The products were purified by column chromatography. The original Suzuki method comprising NaOEt/EtOH, tetrakis(triphenylphosphine)palladium, in toluene was applied only in a few cases, resulting in poor yields. In several cases, the Suzuki coupling of substituted aryl iodides with 2-furanboronic acid failed to result in the formation of the expected products using the palladium acetate/tri(o-tolyl)phosphine/aqueous tripotassium phosphate/dimethoxyethan system. But reacting 3-thiophene-boronic acids with the corresponding iodo-benzyloxybenzaldehydes, this method afforded the products in 76-99 % yields. The more powerful tetrakis(triphenylphosphine)palladium/ aqueous cesium carbonate/dimethylformamide system seemed to be more successful in cases of 2-thiophene boronic acid as well as 2- and 3-furan-boronic acids, providing the desired products in 75-93% yield. Twenty-six new compounds were synthesized.

Synthesis and the Antimicrobial Activity of Salt Carbenoid Compounds

Aim. To synthesize aliphatic and aromatic derivatives of salt carbenoid compounds of the series of imidazole, benzimidazole, pyridine, pyrimidine and 1,3,4-oxadiazole containing fluorophenyl, cetyl or adamantyl substituents, and study their antimicrobial (antibacterial and antifungal) activities.Results and discussion. New derivatives of heterocyclic carbenoid salts and zwitterions based on the imidazole, benzimidazole, pyridine, pyrimidine and 1,3,4-oxadiazole heterocyclic systems containing fluorophenyl, cetyl or adamantyl substituents were synthesized. For this purpose, reactions of cyclization of the corresponding diimines with ethoxymethyl chloride (imidazolium salts), quaternization of the corresponding azoles with cetyl bromide or 1-adamantyl bromide in organic solvents (benzimidazolium, pyridinium and 1,3,4-oxadiazolium salts), cyclization of di(1-adamantylamino)alkanes hydrobromides with the orthoformic ester (4,5-dihydroimidazolium and tetrahydropyridinium salts) were used. Zwitterionic compounds were obtained by the reaction of the corresponding azolium salts with phenyl isothiocyanate in the presence of potassium carbonate. Some macrocyclic and adamantyl substituted heterocyclic compounds showed antifungal and antibacterial activities.Experimental part. The structure of the compounds synthesized was proven by 1H and 13C NMR spectroscopy methods. The antimicrobial activity was studied out by the agar diffusion method to determine diameters of the growth inhibition zones of microorganisms (bacteria and fungi) and by the method of serial dilutions to determine the minimum inhibitory concentration and minimum bactericidal and fungicidal concentrations.Conclusions. The synthesis of new heterocyclic carbenoid salts and zwitterions based on the imidazole, benzimidazole, pyridine, pyrimidine and 1,3,4-oxadiazole heterocyclic systems containing fluorophenyl, cetyl or adamantyl substituents has been performed. Compounds of macrocyclic and adamantyl heterocyclic series with antifungal and antibacterial activities have been found. 1,3-Dicetylimidazolium bromide, macrocyclic bis(decylenebenzimidazolium) bromides, azolium-N-phenylthiocarboximides have been proven to be the most active.

Synthesis of Novel Benzoxazole Derivatives: Exploration of Their Possible Pharmacological Profiles with Computational Studies

Based on the interaction with PDB protein 1PXX of the cox-2 enzyme, a novel series of substituted thiazolidinones (TZD 5a-s) and azetidinones (AZT 6a-s) was designed and synthesized. Molecules were synthesized from 2-mercapto benzoxazole (1) using both conventional and microwave irradiation methods, and their in-vitro antioxidant activity was evaluated using the DPPH free radical scavenging activity, as well as their in-vivo anti-inflammatory activity using the carrageenin-induced rat paw edema method. The reaction time, yield, and purity of microwave and conventionally produced molecules are compared in this work. The molecule ethyl 2-(benzoxazol-2-ylthio)acetate (2) is obtained by reacting 2-mercapto benzoxazole (1) with ethyl 2-chloroacetate in the presence of potassium carbonate and dry acetone. The molecule 2-(benzoxazol-2-ylthio)acetohydrazide (3) was synthesized by reacting ethyl 2-(benzoxazol-2-ylthio)acetate (2) with hydrazine hydrate in the presence of absolute alcohol. Compound 2-(benzoxazol-2-ylthio)acetohydrazide (3) on reacting with different aromatic and heterocyclic aldehyde derivative forms 2-(benzoxazol-2-ylthio)-N'-substituted acetohydrazide Schiff bases (4a-s). 2-(benzoxazol-2-ylthio)-N-(4-oxo-2-substituted thiazolidin-3-yl)acetamide (5a-s) i.e. thiazolidinones benzoxazole derivatives obtained on reacting Schiff bases (4a-s) with thioglycolic acid in a dioxane medium and anhydrous zinc chloride. The Schiff bases (4a-s) were converted into 2-(Benzo[d]oxazol-2-ylthio)-N-(3-chloro-2-oxo-4-substituted azetidin-1-yl)acetamide (6a-s) after treatment with chloroacetyl chloride in the presence of triethanol amine and dioxane. This study focuses on screening of novel synthesized benzoxazole derivatives for in vitro antioxidant, in vivo anti-inflammatory activity, and the evaluation of ulcerogenic activity. The in vivo activity is correlated with the in silico activity, the 3 D QSAR studies were performed for all the compounds by using computer program i.e. SYBYL-X 2.1.1 software. The best CoMFA and CoMSIA models were obtained for the training set compounds with 0.753 and 0.646 leave-one-out coefficients (q2), 0.714 and 0.619 cross validated correlation coefficients (r2cv), and 0.975 and 0.983 conventional coefficients (r2), respectively. Both models were validated with a test set of eight compounds, giving the CoMFA and CoMSIA models a satisfactory prediction (r2pred) of 0.788 and 0.663, respectively. The findings of the study would provide valuable information for the design of new compounds and would also help in predicting the activity of designed compounds. To identify the lead molecule docking studies are performed on COX-2 enzyme of protein 1PXX, the molecules 5c, 5q, 5j, 6q, and 6 g derivatives obtained good - c-docker interaction energy respectively, and in vivo acute ulcerogenic activity.