Presence Of Anhydrous Potassium Carbonate Research Articles

Design, Synthesis and In vitro Screening of Novel 2-Mercaptobenzothiazole- Clubbed Phenylacetamides as Potential Antibacterial Agents

Background: The frightening rise of bacterial resistance is occurring worldwide and endangering the efficacy of antibiotics. Hence, the development of novel and potent antibacterial is a need of the day. Objective: In this study, we designed and synthesized compounds C1-C11. These compounds are characterized by their FT-IR, NMR and MS spectral data and examined in vitro for their antibacterial activity. Methods: Compounds C1-C11 were synthesized by reacting 2-mercaptobenzothiazole with appropriate chloroacetamide in the presence of anhydrous potassium carbonate and dry acetone at room temperature. To assess the antibacterial activity, minimum inhibitory and minimum bactericidal concentrations were examined by broth microdilution method against the selected strains of both Gram-positive and Gramnegative bacteria. Time-kill kinetics study was also performed as per CLSI guidelines. Results: Compounds C6 and C7 displayed promising activity against Staphylococcus aureus ATCC 43300 with MICs of 9.43 and 7.73 μM, respectively. These two compounds also displayed promising antibacterial activity against S. aureus 5021 with MIC values of 7.53 and 9.68 μM, respectively. In MBC determination, these two compounds (tested in the concentration range of 7.53 to 262.3 μM) displayed bactericidal activity against methicillin resistant S. aureus ATCC 43300, S. aureus NCIM 5021 and S. aureus NCIM 5022. In time-kill kinetics study, compounds C6 and C7 also exhibited bactericidal activity against S. aureus NCIM 5021 and S. aureus ATCC 43300 after 12 h of exposure. In general, all tested compounds exhibited poor activity against Mycobacterium sp. NCIM 2984 and also against tested Gramnegative bacteria Klebsiella pneumoniae NCIM 2706, Escherichia coli NCIM 2065 and Pseudomonas aeruginosa NCIM 2036. Further, computed ADMET properties of C1-C11 showed a favourable pharmacokinetic profile with zero violation of Lipinski’s rule of five. Conclusion: The result showed that in phenylacetamides C6 and C7 presence of phenyl ring substituted with -CF3 group is responsible for their high antibacterial activity against S. aureus ATCC 43300 (MICs, 9.43 and 7.73 μM, respectively). These two compounds also exhibited bactericidal activity respectively against S. aureus NCIM 5021 in time kill kinetics study.

In vitro Studies of Antibacterial and Antifungal Activity of Novel Substituted Benzimidazole Derivatives

A series of 2-substituted amino-1-(1H-benzo[d]imidazol-1-yl)ethanone was prepared by reacting with benzimidazole and chloroacetyl chloride by stirring method. The resultant compound was dissolved in ethanol and refluxed with aryl/aralkyl amine in the presence of anhydrous potassium carbonate. The tested compounds were evaluated against bacterial agents such as E. coli, P. aeruginosa, K. pneumonia, S. typhi, and S. aureus, amoxicillin has been used as a control drug, and also screened for antifungal activity against C. albicans and A. niger at 50 and 100 mg/mL level, griseofulvin used as control drug. The structure-activity relationship led to the conclusion compound PS3 showed equipotent potent, PS4 showed moderate, and PS2 showed less moderate activity. The aromatic/aliphatic chain containing compounds PS1 and PS5 showed the least activity against all bacteria. Compound PS3, PS4 and PS1 showed better activity against C. albicans at 100 µg/mL concentration. The tested compounds PS1, PS3, PS2 and PS4 showed good activity at 100 µg/mL concentration. The compound PS3 can serve as a lead molecule for further development as a new class of antimicrobial agent. GRAPHICAL ABSTRACT

Synthesis, Spectroscopic (FT‐IR, FT‐Raman), Electronic Properties and Molecular Docking Studies of 1‐(2, 6‐dibromo‐4‐methyl‐phenoxymethyl)‐benzo[f]chromen‐3‐one

AbstractHerein, 1‐(2,6‐dibromo‐4‐methyl‐phenoxymethyl)‐benzo[f]chromen‐3‐one (DBMPBC) is chosen to be thoroughly investigated in terms of structural, spectroscopic (FT‐IR, FT‐Raman) and molecular electronic properties based on density functional theory (DFT). The title molecule is synthesized by the reaction of 5,6‐benzo‐4‐bromomethylcoumarin with 2,6‐dibromo‐4‐methylphenol in presence of anhydrous potassium carbonate in dry acetone. All the computational studies for the selected structure are carried out at the theoretical level DFT/B3LYP/6‐311++G (d, p). The theoretically determined geometrical parameters from optimized structure and experimental values are compared to each other to confirm the structural properties of the molecule. The vibrational wavenumbers are studied by FT‐IR and FT‐Raman spectral techniques in both experimental and computational methods and compared to each other. The detailed vibrational assignments are assigned through potential energy distribution method by VEDA. The MEP surface analysis is carried out in order to identify the potential sites of electrophilic and nucleophilic attack. The Natural Bond Orbital (NBO) study significantly verified the existence of the intermolecular interactions in the molecule. The stability and reactivity properties of the molecule are estimated in terms of HOMO‐LUMO energies. Molecular docking investigations are carried out to simulate the inhibitory impact of the title molecule against the VEGFR2 (PDB: 2XIR) and PI3K (PDB: 2RDO) receptors for anti‐angiogenic therapy in the treatment of NSCLC. ADMET parameters and toxicity properties of the title molecule is conducted.

Synthesis, spectroscopic (FT-IR, FT-Raman), solvent effects (absorption, fluorescence), electronic and biological evaluation of 7-methyl-4-(4-methyl-2-nitro-phenoxymethyl)-2H-chromen-2-one

In this work, the 7-methyl-4-(4-methyl-2-nitro-phenoxymethyl)-2H-chromen-2-one (7MMNPC) is synthesized by the reaction of 7-methyl-4-bromomethylcoumarin with 4-methyl-2-nitro-phenol in presence of anhydrous potassium carbonate using dry acetone as solvent. Then, it is characterized by several spectral and photophysical properties. Most of the analyses have been investigated by experimental and theoretical methods. Initially, molecular structural characteristics have been obtained by optimized structure with DFT/B3LYP/ 6–311++G (d, p) basis set and compared with reported experimental data. The fundamental vibrational modes of the molecule are fully assigned and examined by observed FT-IR and FT-Raman data and compared with harmonic vibrational wavenumbers obtained by the DFT method. The photophysical properties analyses have been conducted to measure the dipole moments in the ground (μg) and excited (μe) state. The Frontier Molecular Orbital (FMO) analysis depicts that energy gap of HOMO- LUMO is 4.04 eV. Molecular Electrostatic Potential (MEP) analyses are carried out to investigate the molecule's electronic properties. The ADMET and pharmacokinetic parameters are calculated to determine whether the synthesized compound has the potential to be a drug. The toxicological properties of the compound have been investigated. The molecular docking study is conducted to determine the molecule's good degree of inhibition against non-small cell lung cancer (NSCLC).

Design, synthesis, and cytotoxic activity of some novel N-(substituted) benzamide derivatives bearing coumarin and 1-azocoumarin compounds

ABSTRACT. Among oxygen-containing heterocyclic compounds such as coumarin and azacoumarin derivatives, the scaffold has become an important construction motif for developing new drugs. Coumarin and its derivatives possess many types of biological activities and have been reported to show significant cytotoxic activity. N-(6,8-disubstituted coumarin-3-yl)benzamides (8a-c) namely (3-N-(benzoyl) aminocoumarin-6-ylmethyl acetate (8a); N-[6-(1-acetylpyrazol-3-yldiazineyl) coumarin-3-yl] benzamide (8b); N-(8-methoxy-6-bromo-coumarin-3-yl) benzamide (8c), were synthesized via a cyclocondensation reaction of 5-(chloromethyl)-2-hydroxybenzaldehyde (3), 5-(pyrazol-3-yl-diazineyl)-2-hydroxybenzaldehyde (4), and 5-bromo-3-methoxy- 2-hydroxybenzaldehyde (5) with N-benzoylglycine (7), in good yield. Treatment of compound 8c with ammonia in the presence of anhydrous potassium carbonate to yield N-(5-bromo-8-methoxy-1-azocoumarin-3-yl) benzamide (9). Compound (9) was acetylated with acetic anhydride to give N-(2-acetoxy-5-bromo-8-methoxyquinolin-3-yl) benzamide (10). N-(substituted coumarin and azacoumarin-3-yl) benzamides (8-10) were tested for their in vitro cytotoxic activity against (HepG2) cell line. Furthermore, DNA flow cytometry investigation over HepG2 cells indicated that compound 8a demonstrated arrest at G1/S stages of the cell cycle and induction of apoptosis by rising pre-G1 stage. Compound 8a displayed a significant tubulin polymerization inhibition.
 
 KEY WORDS: Synthesis, Coumarin, Azacoumarin, Drugs, Cytotoxicity
 Bull. Chem. Soc. Ethiop. 2023, 37(4), 1003-1019. 
 DOI: https://dx.doi.org/10.4314/bcse.v37i4.16

Synthesis, characterization and biological study of some new substituted pyrazolo[3,4-d] thiazolo[3,2-a] pyrimidine derivatives

Fused pyrimidines play an imperative role in our life due to their biological importance in the struggle of microorganisms. A series of 4-aryl-3-methyl-1-phenyl-1,4,6,7-tetrahydropyrazolo[3,4-d] thiazolo[3,2-a]pyrimidine (4a-j) were synthesized by cyclization of 3-methyl-1-phenyl-4-aryl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-d]pyrimidine-6-thiones (3a-j) with 1,2-dibromoethane in presence of anhydrous potassium carbonate. Earlier, compounds (3a-j) were synthesized by the condensation of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one (2), different substituted benzaldehyde and thiourea with catalytic amount of con. HCl in methanol. Compound 2 was synthesized by condensation of ethyl acetoacetate (1) and phenylhydrezine in presence of a catalytic amount of acetic acid at reflux temperature. The constitution of the synthesized products has been characterized by using elemental analysis, Infrared, 1H-NMR spectroscopy and further supported by Mass spectroscopy. All the products have been screened for their in-vitro biological assay like antibacterial and antifungal activity at concentration of 500 μg/ml. It was exposed that most of the compounds displayed inspiring antibacterial and antifungal activity compared to the used reference standard.

Synthesis and Antimicrobial Evaluation of Quinazoline-4[3H]-one Derivatives

The present investigation aimed to synthesize quinazoline-4(3H)-one derivatives (B1-10) and evaluated their antimicrobial activity. The test compounds (B1-10) were obtained by reaction of 2- phenyl-4H-benzo[d] [1, 3]oxazin-4-one (1) with 4-aminophenol (2) to afford 3-(4-hydroxyphenyl)-2- phenylquinazoline-4(3H)-one (3) which were further reacted with different N-phenylacetamide (4) in the presence of anhydrous potassium carbonate and a catalytic amount of potassium iodide in ethylmethylketone. The test compounds (B1-10) were characterized by the spectroscopic method and evaluated for their antimicrobial activity using the cup plate method by measuring the zone of inhibition. Among the compounds, compound B1, B2, B4, B6, and B8 showed maximum zone of inhibition as compared to standard drug ciprofloxacin and fluconazole against Bacillus subtilis, Escherichia coli and Aspergillus niger. Molecular docking was also performed for test compounds to predict their binding affinities in the target protein and results showed good drug-like properties.

Synthesis and Characterization of Some New Coumarin Derivatives as Probable Breast Anticancer MCF-7 Drugs

This study aimed to synthesize quinolinone derivatives and investigate their cytotoxic activity. The compound 1-azacoumarin-3-carboxylic acid (2-oxo-1H-quinoline-3-carboxylic acid) was obtained via the cyclocondensation of 2-hydroxybenzaldehyde with diethyl malonate in base catalyst to give ethyl coumarin-3-carboxylate, followed by the ammonolysis of ester (ethyl coumarin-3-carboxylate) with ammonia in the presence of anhydrous potassium carbonate. Treatment of 2-oxo-1H-quinoline-3-carboxylic acid with acetic anhydride, cinnamaldehyde, cinnamic acid and methyl 5-phenyl-2-cyano-2,4-pentadienoate under different conditions led to the formation of 1 (substituted) aza coumarin-3-carboxylic acids (1-N-(acetyl)-azacoumarin-3-carboxylic acid, 1-N-(2-Formyl-1-phenyl) vinyl-azacoumarin-3-carboxylic acids, 1-N-[2-(Hydroxy) carbonyl-1-(Phenyl) vinyl]-azacoumarin-3-carboxylic acid and 1-N-(4-Cyano-5-methoxy-5-oxo-1-Phenylpenta-1,3-diene-1-y)-azacoumarin-3-carboxylic 284 acid), respectively. The structures of synthesized 1-(substituted) azacoumarin-3-carboxylic acids were confirmed based on spectroscopic methods (IR and NMR), along with elemental analyses. Interestingly compound 6 demonstrated probable impacts as an anti-cancer drug against the MCF-7 cell line. The mechanism of action was assessed using a flow cytometric assay. The outcomes revealed that compound 6 could arrest the cell cycle at G2/M phase and pre-G1 apoptosis.

New poly(aryl ether ketone)s containing 2,6-diphenylpyridyl units and diphenylphosphinophenyl pendant groups

4-(4-Diphenylphosphino)phenyl-2,6-bis(4-hydroxyphenyl)pyridine, as a new bisphenol monomer, was prepared from 4-(diphenylphosphino)benzaldehyde and 4-hydroxyacetophenone and used in the preparation of several aromatic poly(ether ketone)s (PEKs) containing 2,6-diphenylpyridyl units and diphenylphosphinophenyl pendant groups via a nucleophilic aromatic substitution polycondensation with difluorinated aromatic ketones. The polycondensation proceeded quantitatively in tetramethylene sulfone in the presence of anhydrous potassium carbonate and afforded the polymers with high molecular weights. The resulting PEKs are amorphous and exhibit high glass transition temperatures of 209–255°C and 5% weight loss temperatures of 536–554°C with char yields of 57–62% at 800°C in nitrogen. Their high char yields and good limited oxygen index values ranging from 39 to 43 indicated these polymers exhibited good thermal stability and flame-retardant property. All new PEKs were soluble in common organic solvents such as N-methyl-2-pyrrolidone, N,N-dimethylacetamide, and chloroform and could form tough, flexible, and strong films with tensile strengths of 74.6–86.8 MPa, tensile moduli of 2.9–3.6 GPa, and elongations at break of 5–9%.

2D-QSAR study of synthesized novel derivatives of 1,3,4- Oxadiazoles as anti-inflammatory activity

Oxadiazole is a five-membered heterocyclic compound containing oxygen and two nitrogen atoms at C-1, C-3 and C-4 positions respectively. These derivatives are synthesized by both conventional as well as microwave-assisted. 1,3,4-Oxadiazole have reported a wide spectrum of activities such as antibacterial, antimalarial, anti-inflammatory, antioxidant, antipyretic, and antihypertensive activities Hence, some new 1,3,4–oxadiazoles will be synthesized from 4-(morpholine-4-yl) benzohydrazide (Compound IV) refluxed with ethyl chloroformate followed by amino acid and hydrazine hydrate gives 2-({5-[4-(morpholine-4-yl) phenyl]-1,3,4-oxadiazol-2-yl}amino) acetohydrazide (Scheme-IV) which is treated with aromatic aldehyde gives 1,3,4-oxadiazoles derivatives. Compound IV refluxed with ethyl chloroformate in presence of anhydrous potassium carbonate gives an intermediate product which is treated with phosphoric tri-chloride followed by thionyl chloride gives 4-[4-(5-chloro-1,3,4-oxadiazol -2-yl)phenyl] morpholine (Scheme-V) it undergoes reflux with substituted aromatic aldehydes in presence of anhydrous aluminium trichloride in ethanol or THF (tetrahydrofuran) gives 1,3,4-oxadiazoles derivatives. These synthesized compounds were subjected to 2D-QSAR study. A series of 28 molecules belonging to 2-({5-[4-(morpholine-4-yl) phenyl]-1,3,4-oxadiazol-2-yl}amino) acetohydrazide reaction scheme-SMRB4 and 4-[4-(5-chloro-1,3,4-oxadiazol-2-yl)phenyl] morpholine reaction scheme-SMRB5 derivatives Anti-inflammatory were taken and used. The 2D-QSAR Models were generated using a training set of molecules by MLR (Multiple regressions) 2D-QSAR method.

Синтез и исследование свойств 7-замещенных теофиллинов

In the present study 7-(2-bromoallyl)- and 7-cinnamyltheophylline have been obtained by the interaction of alkenylhalides with theophylline in DMF in the presence of anhydrous potassium carbonate at 100 ºС in water bath. Fragmentation under electron ionization of the obtained 7-alkenyltheophyllines has been investigated by gas chromatography–mass spectrometry analysis, the main molecule fragmentation ways have been revealed. The mass spectra have been obtained on an UltraShimadzu GCMS-QP2010 and an Agilent 6890 N. The cinnamyl cation peak has the maximum intensity in the 7-cinnamylteophylline mass spectrum. The formation of tropylium cation ( m/z 91) is characteristic for the 7-cinnamylteophylline mass spectrum. In the case of 7-(2-bromoallyl)theophylline the elimination of bromine radical leads to formation of the peak with the maximum intensity. 7-(2,2,3-Tribromopropyl)theophylline and 7-(2,3-dibromo-3-phenylpropyl)theophylline have been synthesized by the addition of bromine to the double bonds of 7-(2-bromoallyl)- and 7-cinnamyltheophylline in CHCl 3 at room temperature. The structures of reaction products have been confirmed by 1 H NMR spectroscopy and gas chromatography–mass spectrometry. The structure of 7-(2,2,3-tribromopropyl)theophylline has been confirmed by X-ray analysis. The crystal contains two types of crystallographically independent molecules, the geometric parameters of which slightly differ. There is characteristic distribution of the molecular ion isotope peaks in the mass spectra of halogen-containing compounds: a doublet with an intensity ratio of approximately 1:1 for compounds with one bromine atom, a triplet of peaks in the case of two bromine atoms, and a quartet with an intensity ratio 1:3:3:1 for tribromoderivatives. In the case of 7-propargyltheophylline the reaction with bromine stops at the addition of one bromine molecule, which is proved by the formation of 7-(2,3-dibromoallyl)theophylline. It has been confirmed by 1 H NMR and chromatography–mass spectrometry. Interaction of 7-(2,3-dibromopropyl)theophylline with o -phenylenediamine in acetonitrile at room temperature leads to the formation of quinoxaline ring. The 1 H NMR spectrum contains characteristic signals of aromaticprotons at δ 6.85–7.05 ppm.

Synthesis and Characterization of Bioactive Cadmium (II) Complexes Derived from 4-Benzyloxybenzoylhydrazine with Different Aromatic Aldehydes

The reactions of the ligand precursor 4-benzyloxybenzoylhydrazine (2) with cinnamaldehyde, salicylaldehyde, 2,4-dimethoxybenzaldehyde, 4-N,N dimethylaminobenzaldehyde, 4-methoxybenzaldehyde formed the ligands C6H5CH2OC6H4CONHN=CHR, where R=C6H5CH=CH, (3); C6H4(OH), (4); C6H3(OCH3)2, (5); C6H4N(CH3)2, (6); C6H4(OCH3), (7), respectively. The ligand precursor 4-benzyloxybenzoylhydrazine (2) was synthesized by the condensation reaction of ethyl-4-benzyloxybenzoate (1) with hydrazine hydrate. Ethyl-4-benzyloxybenzoate (1) was synthesized by the reaction of ethyl-4-hydroxybenzoate and benzyl bromide dissolved in acetone in presence of anhydrous potassium carbonate. By the reactions of the synthesized ligands with cadmium(II) acetate, a series of complexes [(C6H5CH2OC6H4CONHN=CHR)2Cd] were obtained, where R=C6H5CH=CH, (8); C6H4(OH), (9); C6H3(OCH3)2, (10); C6H4N(CH3)2, (11); C6H4(OCH3), (12). The complexes cannot be obtained via a template method. The compounds have been characterized by elemental analysis, conductivity measurements, UV-visible, FT-IR, 1H NMR spectral studies. The conductivity measurement data revealed that the complexes are non-electrolytic in nature. The UV-visible data of the complexes suggested the tetrahedral geometry of Cd(II) ion. The antibacterial results of the ligands (3-7) exhibited very low or no activity against pathogenic bacteria viz. gram positive (Bacillus anthracis, Staphylococcus aureus, Bacillus megaterium) and gram negative (Shigella flexneri, Escherichia coli, Shigella shiga), whereas their corresponding complexes (8-12) exhibited activity against the aforementioned bacteria but less than the standard drug, kanamycine. This implies that the activity showed by the complexes is solely responsible for the presence of Cadmium (II) ion.

Synthesis and Antioxidant Activity of Novel 5-amino-2-alkyl/glycosylthio-1,3,4- thiadiazoles: Regioselective Alkylation and Glycosylation of the 5-amino-1,3,4- thiadiazole-2-thiol Scaffold.

5-Amino-2-alkyl/glycosylthio-1,3,4-thiadiazoles have been synthesized by the reaction of 5-amino-1,3,4-thiadiazole-2-thiol with a variety of alkylating agents or glycosyl halides in the presence of anhydrous potassium carbonate in dry acetone. The structures of the newly synthesized compounds have been established based on their spectral data (FT-IR, 1H- and 13C-NMR) and mass spectrometry. They were tested for their antioxidant behaviour by the use of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. The in silico pharmacokinetics ADME properties of the potent antioxidant compounds were investigated by using Accelrys Discovery Studio (DS) 2.5 software. Regioselective alkylation and glycosylation of 5-amino-1,3,4-thiadiazole-2-thiol were noticed during its reaction with alkylating agents and glycosyl halides. Alkylating agents gave the Sfunctionalized derivatives, while the acetylated glycosyl halides afforded the S-glycosylated products together with their respective N-acetyl derivatives. The benzoylated glycosyl halide behaved in a different manner and gave N-glycoside analogue of 1,3,4-thiadiazole-2(3H)-thione, in addition to the expected sulfanyl S-glycoside. Most of the synthesized compounds showed noticeable antioxidant activity with respect to ceftriaxone as a standard drug. Some of the most active compounds showed acceptable predicted pharmacokinetics and druglikeness properties.

New Biphenyl‐Based Bispyrazolines: Synthesis, Antimicrobial, and Docking Studies

In this study, a series of new bispyrazolines 8(a–f) have been prepared from the cyclization reactions of bischalcones 7(a–f) with phenyl hydrazine by refluxing under the alkaline alcoholic (KOH/EtOH) conditions. The O‐alkylation reactions of hydroxyl substituted chalcone 6 with different 1,ω‐dibromoalkanes in the presence of anhydrous potassium carbonate, tetrabutylammonium iodide, and dry acetone afforded the symmetrical new bischalcones 7(a–f) in good yields. Chalcone 6 was realized by using the Claisen–Schmidt reaction of m‐hydroxyacetophenone with bipheny‐4‐carboxaldehyde. The various spectroscopic parameters such as IR, 1H‐NMR, 13C‐NMR, and ESI‐MS have been thoroughly used for the structural interpretations of the newly prepared products. The in vitro antibacterial and antifungal activities of these compounds have been examined with the help of serial tube dilution method, and many of the tested products were found to be revealing the promising antimicrobial properties, which were evident from their minimum inhibitory concentration values. The molecular docking simulations of the synthesized substances have also been achieved to observe the structural association into the active site of the Escherichia coli FabH (PdB: 3IL9). Docking results of these compounds suggested that bispyrazoline 8b demonstrated the lowest binding energy that describes its higher stability into the pocket of E. coli. The excellent inhibitory activity of this bisheterocycle against E. coli FabH may be ascribed on the basis of hydrophobic and van der Waals interactions.

Synthesis and Research of Properties of Polyether Ether Ketone

Polyether ether ketones based on 4,4'-difluorobenzophenone and hydroquinone in sulfolane medium in the presence of anhydrous potassium carbonate were synthesized by the method of high-temperature polycondensation. The rheological, thermal, electrical and physical-mechanical properties are investigated. It is shown that, at processing temperatures, the molecular weight of polyether ether ketones synthesized in sulfolane increases, apparently due to the branching processes of the polymer chain.

Synthesis and mass spectrometry of some arylidene-hydrazinyl-thiazolines and their 2-arylidene-N-(3-chlorophenyl)hydrazinecarbothioamide precursors

N-(3-Chlorophenyl)hydrazinecarbothioamide (2) was prepared by reacting 1-chloro-3-isothiocyanatobenzene (1) with hydrazine hydrate in 2-propanol, whose 1H-NMR spectrum showed its existence in a Zwitter ionic betain form. A number of 2-arylidene-N-(3-chlorophenyl)hydrazinecarbothioamides (3a–e) were synthesized by the condensation of 2 with aromatic aldehydes in absolute ethanol and in the presence of a catalytic amount of glacial acetic acid. They were reacted with 2-bromo-1-(4-bromophenyl)ethanone (4) in 2-propanol/DMF in the presence of anhydrous potassium carbonate to produce the respective 2-(arylidenehydrazono)-4-(4-bromophenyl)-3-(3-chlorophenyl)-2,3-dihydrothiazoles (5a–e) in excellent yields. The synthesized compounds were characterized by spectroscopic methods as well as mass spectrometry. The molecular modeling and atomic charges of heteroatoms in all compounds were performed using Chem3D Pro 12.0.2 software and provided an excellent tool to investigate the fragmentation pathways. The nitrogen rule was also found to be good predictors of molecular ions and their fragmentation patterns.

Synthesis, biological evaluation and molecular docking study of 1,2,3-1H-triazoles having 4H-pyrano[2,3-d]pyrimidine as potential Mycobacterium tuberculosis protein tyrosine phosphatase B inhibitors

Some heterocycles, namely 2-amino-4H-pyran-3-carbonitriles, were synthesized in a three-component reaction from substituted benzaldehydes, malononitrile, and ethyl acetoacetate. These heterocycles have been converted subsequently into 4H-pyrano[2,3-d]pyrimidine ring by ring-closing reaction with acetic anhydride in the presence of the concentrated sulfuric acid as catalyst. The successive alkylation reaction of lactam NH bond on pyrimidine-4-one ring was carried out using propargylic bromide in dry acetone in the presence of anhydrous potassium carbonate. The click chemistry of 3-propargyl-4H-pyrano[2,3-d]pyrimidine compounds has been accomplished by reaction with tetra-O-acetyl-α-d-glucopyranosyl azide using the metal-organic framework Cu@MOF-5 as a catalyst in absolute ethanol. All the synthesized 1H-1,2,3-triazoles 8a–y were screened for their in vitro Mycobacterium tuberculosis protein tyrosine phosphatase B (MtbPtpB) inhibition. Kinetic studies of the most active compounds 8v, 8x, and 8y showed their competitive inhibition toward the MtbPtpB enzyme. The detailed structure-activity relationship (SAR) in vitro and in silico studies suggested that the interaction of Arg63 amino acids with anion type of para-hydroxyl group via a salt bridge of iminium cation was essential for strong inhibitory activity against MtbPtpB.

Synthesis and Characterization of Poly(ether ether ketone-co-benzimidazole)s Based on 2-(2'-Hydroxyphenyl) benzimidazole

A series of novel poly(ether ether ketone)s containing benzimidazole groups with precise structures in high yields were synthesized from various stoichiometric ratio mixtures of m-dihydroxybenzene, 2-(2'- hydroxyphenyl)benzimidazole and 4,4′-difluorodiphenylmethanone via a C–N/C–O coupling reaction process using sulfolane as a solvent. The reaction was carried out at 210°C in the presence of anhydrous potassium carbonate. The structures of the resulted polymers were characterized by means of FTIR, 1H NMR spectroscopy, elemental analysis, and the results were largely consistent with the proposed structure. XRD studies indicated that the resulted polymers are non-crystalline. The polymers have good solubilities in common organic solvents. The polymers showed high glass transition temperatures (Tg = 125–237°C) and high thermal stability (Td5% = 497–539°C in nitrogen, 466–548°C in air). At the same time, as the benzimidazole unit content in the copolymer increased, the thermal properties of the prepared polymers improved. Moreover, the resulted polymers showed good fluorescence properties and the fluorescence emission peak was 465 nm.

Synthesis and properties of novel organosoluble copoly(arylene ether nitriles) containing thioether moiety

In this work, a series of novel organosoluble copoly(arylene ether nitriles) containing thioether moiety (PENS) were synthesized via nucleophilic aromatic substitution polymerization of 2,6-dichlorobenzonitrile with bisphenol A and sodium sulfide nonahydrate, using N-Methyl-2-Pyrrolidone as solvent in the presence of anhydrous potassium carbonate. The chemical structures of PENS were characterized by FTIR and 1H NMR. The derived copolymers showed high glass transition temperatures in the range of 167–178 °C and excellent thermal stability with the 5% weight loss temperatures ranging from 465 °C to 503 °C. Meanwhile, all of the PENS were amorphous and can be readily cast into transparent films with a tensile strength exceeding 77 MPa and a breaking elongation over 4.8%.In addition, the dielectric constant of all the PENS copolymers showed weak frequency dependence, the dielectric loss showed slight decrease with increasing frequency over the range of 100 Hz to 200 kHz. Therefore, this kind of organosoluble copoly(arylene ether nitriles) containing thioether moiety could be a good candidate as matrix resins for high-performance polymeric materials.

Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers

Abstract Objective The aim of this study was to synthesize ten 1,4-dihydropyridine (DHP) derivatives in which substituted cyclohexane rings were fused to the DHP ring and to determine how different ester groups and the benzoyl substituent introduced in 4-phenyl ring affected their calcium channel blocking activity. Methods A microwave-assisted one-pot method was applied for the synthesis of compound 1–5 according to a modified Hantzsch reaction. The benzoyl moiety was introduced in the 4-phenyl ring of these dihydropyridines by refluxing with benzoyl chloride in acetone in the presence of anhydrous potassium carbonate. Synthesized products were characterized by elemental analysis, IR, 1H-NMR and 13C-NMR spectroscopy. The inhibitory actions of compounds 1–10 on calcium channel blocking activity were tested on isolated rat aorta preparations. Results The obtained pharmacological results showed that although all compounds are potent relaxing agents on isolated rat aorta smooth muscle, introduction of a benzoyloxy substitiuent on the phenyl ring (compound 6–10) decreased the relaxant effect of these compunds. Conclusion The reported 1,4-DHP derivatives have calcium channel blocking activity on rat aorta smooth muscle.