Green approach for the synthesis of 3‐methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol 3‐yl)methylene)‐1H‐pyrazole‐5(4H)‐ones and their DNA Cleavage,antioxidant, and antimicrobial activities

3‐Methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol‐3‐yl)methylene)‐1H‐pyrazol‐5(4H)‐ones (5a‐i) was prepared by the condensation reaction of different 3‐formyl‐2‐phenylindole derivatives (2a‐i) and 3‐methyl‐1‐phenyl‐2‐pyrazoline‐5‐one in quantitative yield by applying various green synthetic methods as grinding, microwave irradiation using different catalysts under solvent‐free mild reaction conditions with high product yields. The structures of the synthesized compounds were characterized on the basis of elemental analysis, infrared, ¹HNMR, ¹³C NMR, and mass spectral data. The synthesized compounds were screened for free radical scavenging, antimicrobial, and DNA cleavage activities. Most of the tested compounds belonging to the 3‐methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol‐3‐yl)methylene)‐1H‐pyrazol‐5(4H)‐ones series exhibited promising activities.     

Novel Bis(2‐(5‐((5‐phenyl‐1H‐tetrazol‐1‐yl)methyl)‐4H‐1,2,4‐triazol‐3‐yl)phenoxy)Alkanes: Synthesis and Characterization

In this study, 10 different substituted aromatic bis‐benzaldehydes were synthesized by treating hydroxy benzaldehydes with various dihaloalkanes. Bis aldehydes 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j were treated with 2‐(5‐phenyl‐1H‐tetrazole‐1‐yl)acetohydrazide ( 3 ) in acidic medium and in the presence of ammonium acetate to yield a series of new isomeric bis(2‐(5‐((5‐phenyl‐1H‐tetrazol‐1‐yl)methyl)‐4H‐1,2,4‐triazol‐3‐yl)phenoxy)alkanes ( 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j ) in excellent to good yield. The newly synthesized compounds were characterized by the available spectroscopic analysis.     

Design,Synthesis, Characterization,and Antimicrobial Evaluation of Novel 2‐(3, 5‐di methoxy‐4‐((1‐aryl‐1H‐1, 2, 3‐triazole‐4‐yl) methoxy) phenyl) benzo[d]thiazoles

A series of 12 new 2‐(3, 5‐dimethoxy‐4‐((1‐Aryl‐4H‐1, 2, 3‐triazol‐4‐yl) methoxy) phenyl) benzo[d]thiazoles have been synthesized from the reaction of 4‐hydroxy‐3, 5‐dimethoxybenzaldehyde, o‐amino thiophenol, propargyl bromide, and different substituted aromatic azides using “click chemistry”. The structures of these compounds were established on the basis of Fourier Transform infrared, ¹H NMR, ¹³C–NMR, and mass spectral analysis. Compounds ( 6a–l ) were screened for in vitro antimicrobial activity.     

2‐(3,4‐Dichlorophenylimino)‐5‐((3‐(p‐substitutedphenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)methylene)thiazolidin‐4‐one as an Antibacterial,Antifungal and Antimycobacterial Agent

2‐(3,4‐Dichlorophenylimino)‐5‐((3‐(p‐substitutedphenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)methylene) thiazolidin‐4‐one has been selected as a target bio‐active molecules. Newly synthesized compounds were screened with Eschericha coli (MTCC 443), Pseudomonas aeruginosa (MTCC 1688), Staphylococcus aureus (MTCC 96), Streptococcus pyogenes (MTCC 442) for antibacterial, Candida albicans (MTCC 227), Aspergillus niger (MTCC 282), Aspergillus clavatus (MTCC 1323) for antifungal activity and H ₃₇ Rv for antimycobacterial activity. Compounds 3a , 3c , 3d , 3e , and 3h are potentially active against Staphylococcus aureus , while 3h is active against C. albicans . Compounds 3d and 3f are active against H ₃₇Rv for mycobacterium tuberculosis. Other possesses moderate to good activity. The structures of synthesized compounds were firmly established by well‐defined elemental analyses (C, H, N, S/O) and spectral analysis technique likes, IR, ¹H NMR and GC–MS.     

Microwave‐Assisted Synthesis and Antituberculosis Screening of Some 4‐((3‐(Trifluoromethyl)‐5,6‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrazin‐7(8H)‐l)methyl)benzenamine Hybrids

In the present investigation, a series of 4‐((3‐(trifluoromethyl)‐5,6‐dihydro‐[1,2,4]triazolo[4,3‐a]pyrazin‐7(8H)‐yl)methyl)benzenamine analogs 6a–o were synthesized and characterized by IR, NMR (¹H and ¹³C), and mass spectra. All newly synthesized compounds 6a–o were prepared under conventional and microwave irradiation methods. These compounds obtained in higher yields and in shorter reaction times in the microwave irradiation method when compared with the conventional method. Synthesized compounds 6a–o were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis H₃₇Ra using an established XTT reduction menadione assay. Among the screened compounds, 6i (IC₅₀: 1.82 μg/mL), 6j (IC₅₀: 1.02 μg/mL), and 6k (IC₅₀: 1.59 μg/mL) showed excellent activity. Furthermore, compound 6i showed MIC₉₀ value of 16.02 μg/mL. In summary, the results indicate the identification of some novel, selective, and specific inhibitors against M. tuberculosis that can be explored further for the potential antitubercular drug.     

Synthesis and Characterization of Novel 1‐Methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazole Derivatives

A series of novel 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles was synthesized in three steps from 5‐(1‐methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones. 5‐(1‐Methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones were converted into 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles upon methylation followed by treatment with aq. KMnO₄. The reaction of 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles with Raney nickel resulted in desulphonylation to afford corresponding 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles. All the new synthesized compounds were characterized by spectral techniques.     

Synthesis and Cytotoxic Activity of 1‐{3‐[1‐(5‐Organylsilylfuran‐2‐yl)silinan‐1‐yl]propyl}amines and Some Trimethylgermyl Analogues

New highly cytotoxic 1‐{3‐[1‐(5‐organylsilyl‐furan‐2‐yl)silinan‐1‐yl]propyl}amines and some trimethylgermyl analogues (IC₅₀ 1–7 μg mL^?1) have been synthesized by a hydrosilylation reaction of aliphatic and heterocyclic N‐allylamines in the presence of Speier’s catalyst. The effects of the silacycle, the element‐organic substituent in position 5 of the furan ring, and the structure of the amine on the cytotoxicity of the new compounds have been studied.     

Synthesis and Antimicrobial Screening of Some Novel 2‐(5‐(4‐(1H‐Benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)phenols Incorporated by Triazole Moiety

A novel series of 2‐(5‐(4‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)phenols derivative has been synthesized from (E)‐3‐(4‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐1‐(2‐hydroxyphenyl)prop‐2‐en‐1‐ones in ethanol and hydrazine hydrate under reflux condition. The synthesized compounds were screened for antibacterial activity against Gram‐positive bacteria viz Staphylococcus aureus and Bacillus subtilis and Gram‐negative bacteria viz Escherichia coli and Salmonella typhi, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, ¹H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.     

Novel 5‐Methyl‐2‐[(un)substituted phenyl]‐4‐{4,5‐dihydro‐ 3‐[(un)substituted phenyl]‐5‐(1,2,3,4‐tetrahydroisoquinoline‐2‐yl)pyrazol‐1‐yl}‐oxazole Derivatives: Synthesis and Anticancer Activity

Eleven novel 5‐methyl‐2‐[(un)substituted phenyl]‐4‐{4,5‐dihydro‐3‐[(un)substituted phenyl]‐5‐(1,2,3,4‐tetrahydroisoquinoline‐2‐yl)pyrazol‐1‐yl}‐oxazole derivatives were synthesized and characterized by elemental analysis, ESI‐MS, ¹H NMR and ¹³C NMR. All of the compounds have been screened for their antiproliferative activities against PC‐3 cell (human prostate cancer) and A431 cell (human epidermoid carcinoma cancer) lines in vitro. The results revealed that compounds 4g , 4j and 4k exhibited the strong inhibitory activities against the PC‐3 cell lines (with IC₅₀ values of 2.8±0.11, 3.1±0.10 and 3.0±0.06 μg/mL, respectively).     

Synthesis and antibacterial activity of novel series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline

A new series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline were synthesized from oxidative cyclization of N′‐((2‐(p‐tolyloxy)quinoline‐3‐yl)methylene)isonicotinohydrazide in DMSO/I₂ at reflux condition for 3–4 h. The structures of the new compounds were confirmed by elemental analyses as well as IR, ¹H‐NMR, and mass spectral data. All the synthesized compounds were screened for their antibacterial activities against various bacterial strains. Several of these compounds showed potential antibacterial activity. J. Heterocyclic Chem., (2011).     

Synthesis and Fungicidal Activity of 5‐Aryl‐1‐(aryloxyacetyl)‐3‐(tert‐butyl or phenyl)‐4‐(1H‐1,2,4‐triazol‐1‐yl)‐4,5‐dihydropyrazole

A series of novel 5‐aryl‐1‐(aryloxyacetyl)‐3‐(tert‐butyl or phenyl)‐4‐(1H‐1,2,4‐triazol‐1‐yl)‐4,5‐dihydropyrazole 3a – 3n were synthesized by the annulation of 2‐aryloxyacetohydrazides with 3‐aryl‐1‐t‐butyl (or phenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)prop‐2‐en‐1‐ones ( 2 ) in the presence of a catalytic amount of acetic acid. Compounds 2 were obtained by the Knoevenagel reactions of 1‐t‐butyl (or phenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)ethanone ( 1 ) with aromatic aldehydes in the presence of piperidine. Their structures were confirmed by IR, ¹H‐NMR, ESI‐MS, and elemental analyses. The preliminary bioassay indicated that some compounds displayed moderate to excellent fungicidal activity. For example, compounds 3l , 3m , and 3n possessed 100% inhibition against Cercospora arachidicola Hori at the concentration of 50 mg/L.     

Synthesis and Antimicrobial Activity of Novel 2‐Substituted Phenoxy‐N‐(4‐substituted Phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐yl)acetamide Derivatives

A series of 2‐substituted phenoxy‐N‐(4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazole‐2‐yl)acetamide derivatives 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j , 8k , 8l , 8m , 8n , 8o , 8p , 8q , 8r , 8s , 8t was synthesized by the reaction of phenoxyacetyl chloride 7 with intermediate 4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐amine 5 . Their structures were confirmed by ¹H NMR, ¹³C NMR, MS, IR, and elemental analyses. The synthesized compounds were also screened for their antimicrobial activity against three types of plant fungi (Gibberella zeae , Phytophthora infestans , and Paralepetopsis sasakii ) and two kinds of bacteria [Xanthomonas oryzae pv. oryzae (Xoo ) and Xanthomonas axonopodis pv. citri (Xac )] showing promising results. In particular, 8b , 8f , 8g , and 8h exhibited excellent antibacterial activity against Xoo , with 50% effective concentration (EC₅₀) values of 35.2, 80.1, 62.5, and 82.1 µg/mL, respectively, which are superior to the commercial antibacterial agent bismerthiazol (89.9 µg/mL). The preliminary structure–activity relationship studies of these compounds are also briefly described.     

Studies on the Reactivity of Amino‐1‐(6‐phenyl‐pyridazin‐3‐yl)‐1H‐pyrazole‐4‐carboxylic Acid Hydrazide Towards Some Reagents for Biological Evaluation

Novel 5‐amino‐1‐(6‐phenyl‐pyridazin‐3‐yl)‐1H‐pyrazole‐4‐carboxylic acid ethyl ester ( 2 ) was formed using (6‐phenyl‐pyridazin‐3‐yl)‐hydrazine ( 1 ) and ethyl(ethoxymethylene)cyanoacetate. The β‐enaminoester derivative 2 was in turn used as precursor for the preparation of 1‐(6‐phenyl‐pyridazin‐3‐yl)‐pyrazoles ( 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 15 , 16 ), 1‐(6‐phenyl‐pyridazin‐3‐yl)‐pyrazolo[3,4‐d]pyrimidines ( 5 , 6 , 14 ) and 1‐(6‐phenyl‐pyridazin‐3‐yl)‐pyrazolo[3,4‐d][1,2,3]triazine ( 13 ). The in vitro antimicrobial activity of the synthesized compounds was evaluated by measuring the inhibition zone diameters where some of them showed potent antimicrobial activity in compared with well‐known drugs (standards).     

Sulfonamide‐derived compounds and their transition metal complexes: synthesis,biological evaluation and X‐ray structure of 4‐bromo‐2‐[(E)‐{4‐[(3,4‐dimethylisoxazol‐5 yl)sulfamoyl]phenyl} iminiomethyl] phenolate

Sulfonamide‐derived new ligands, 4‐({[(E)‐(5‐bromo‐2‐hydroxyphenyl)methylidene]‐amino}methyl)benzenesulfonamide and 4‐bromo‐2‐((E)‐{4‐[(3,4‐dimethylisoxazol‐5‐yl)sulfamoyl]phenyl}iminiomethyl)phenolate and their transition metal [cobalt(II), copper(II), nickel(II) and zinc(II)] complexes were synthesized and characterized. The nature of bonding and structure of all the synthesized compounds were deduced from physical (magnetic susceptibility and conductivity measurements), spectral (IR, ¹H and ¹³C NMR, electronic, mass spectrometry) and analytical (CHN analysis) data. The structure of the ligand, 4‐bromo‐2‐((E)‐{4‐[(3,4‐dimethylisoxazol‐5‐yl)sulfamoyl]phenyl} iminiomethyl)phenolate was also determined by X‐ray diffraction method. An octahedral geometry was suggested for all the complexes. In order to evaluate the biological activity of the ligands and the effect of metals, the ligands and their metal complexes were screened for in vitro antibacterial, antifungal and cytotoxic activity. The results of these studies revealed that all compounds showed moderate to significant antibacterial activity against one or more bacterial strains and good antifungal activity against various fungal strains. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis and Cytotoxicity in Vitro of N‐Aryl‐4‐(tert‐butyl)‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐amine

A series of novel N‐aryl‐4‐(tert‐butyl)‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐amines synthesized in a green way. H₂O₂‐NaBr Brominating circulatory system was used in the synthesis of the key intermediate in a mild condition. All of the target compounds were confirmed by ¹H NMR and elemental analysis and tested for their cytotoxicity against two different human cancer cell lines. The cytotoxicity assay revealed that some of the title compounds showed moderate to strong cytotoxic activities. Compound 2i was the most potent compound with the IC₅₀ values of 9 μM against Hela cells and 15 μM against Bel–7402 cells, respectively.     

Synthesis of Novel Fluorescent 2‐{4‐[1‐(Pyridine‐2‐yl)‐1H‐pyrazol‐3‐yl] phenyl}‐2H‐naphtho [1,2‐d] [1,2,3] triazolyl Derivatives and Evaluation of Their Thermal and Photophysical Properties

Novel 2‐{4‐[1‐(pyridine‐2‐yl)‐1H‐pyrazol‐3‐yl] phenyl}‐2H‐naphtho [1,2‐d] [1,2,3] triazolyl fluorescent derivatives were synthesized from p‐nitrophenylacetic acid and 2‐hydrazino pyridine through Vilsmeier–Haack and diazotization reactions. Photophysical properties were evaluated, and results show that compounds have good fluorescence quantum yields. Thermal analysis showed that they are reasonably stable. The structures of the compounds were confirmed by FT‐IR, ¹H NMR, ¹³C NMR, and mass spectral and elemental analysis.     

Design,Synthesis, and Evaluation of 3‐((4‐(t‐Butyl)‐2‐(2‐benzylidenehydrazinyl)thiazol‐5‐yl)methyl)quinolin‐2(1H)‐ones as Neuraminidase Inhibitors

A series of novel 3‐((4‐(t‐butyl)‐2‐(2‐benzylidenehydrazinyl)thiazol‐5‐yl)methyl)quinolin‐2(1H)‐ones ( 7a – 7z ) were designed, synthesized and evaluated for their ability of inhibiting neuraminidase (NA) of in?uenza H1N1 virus. Some compounds displayed moderate influenza NA inhibitory activity. Compound 7l with the scaffold of 2‐(2‐(2‐methoxybenzylidene)hydrazinyl)thiazole was the best one, exhibiting moderate NA inhibitory activity with IC₅₀ of 44.66 µmol/L. Structure‐activity relationship showed that compounds with methoxy or hydroxy groups at the ortho position, fluorine and nitro groups at the meta position and chlorine and bromine groups at the para position of phenyl ring were more active. Docking study indicated that compound 7l has important interactions with some key residues (including Asp151, Glu119, Arg292, Tyr406, and Asn347) and binds to 430‐cavity adjacent to NA active site.     

Synthesis and Antimicrobial Screening of 2‐Aryl‐5‐((2‐arylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole Derivatives

A new series of 2‐aryl‐5‐((2‐arylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole derivatives was synthesized by condensation of 2‐(2‐substituted thiazol‐4‐yl)acetohydrazide with aryl aldehydes followed by oxidative cyclocondensation using iodobenzene diacetate. The structure of synthesized compounds was characterized by IR, NMR, and mass analysis. All the newly synthesized compounds were evaluated for their in vitro antimicrobial activity. Some of the compounds showed moderate antimicrobial activity.     

Synthesis and Characterization of New Thebaine Derivatives as Potential Opioid Agonists and Antagonists: 2‐[N‐(1H‐Tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazoles

In this study, we report the synthesis a series of novel 2‐[N‐(1H‐tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazole derivatives ( 7a – e ) which have potential opioid antagonist and agonist. The substitution reaction of 6,14‐endo‐ethenotetrahydrothebaine‐7α‐carbohydrazide with corresponding benzoyl chlorides gave diacylhydrazine compounds 4a – e in good yields. The treatment of compounds 4a – e with POCl₃ caused the conversion of side‐chain of compounds 5a – e into 1,3,4‐oxadiazole ring at C(7) position; thus, compounds 5a – e were obtained. Subsequently, cyanamides ( 6a – e ) were prepared from compounds 5a – e and then compounds 7a – e were synthesized by the azidation of 6a – e with NaN₃. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C APT, 2D‐NMR (COSY, NOESY, HMQC, HMBC) and high‐resolution mass spectral data.     

Synthesis and Characterization of Novel Arylaldehyde (Arylketone)‐(4‐Substituted phenyl‐5‐Substituted phenoxy‐Methyl‐4H‐1,2,4‐Triazole‐3‐yl)‐Thiol Acetyl Hydrazones

Fourteen novel arylaldehyde (arylketone)‐(4‐substituted phenyl‐5‐substituted phenoxy‐methyl‐4H‐1,2,4‐triazole‐3‐yl)‐thiol acetyl hydrazone derivatives ( 5a‐5g, 6a‐6g ) were synthesized by 4‐substituted phenyl‐5‐substituted phenoxy‐methyl‐1,2,4‐triazole‐3‐thione as starting material according to substructure link principle, followed by thioetherification, hydrazide hydrazone reaction. The structures of these compounds were confirmed by IR, ¹H NMR and elemental analysis. Crystal structure of compounds 1b and 6d were determined by the X‐ray diffraction.