Synthesis and Evaluation of Some New (1,2,4) Triazolo(4,3‐a)Quinoxalin‐4(5H)‐one Derivatives as AMPA Receptor Antagonists

This study involves the synthesis and anticonvulsant evaluation of 1‐ethyl‐3‐hydrazinylquinoxaline‐2‐(1H)‐one ( 8 ), its chemical confirmations 9 and 10 and certain (1,2,4) triazolo(4,3‐a)quinoxalin‐4(5H)‐one compounds 11 , 12 , 13 , 13a , 13b , 13c , 13d , 13e , 13f , 14 , 15 , 16 . The structure of the synthesized compounds was confirmed chemically by elemental analyses and spectral data (IR, ¹H NMR, ¹³C NMR, and Mass). Docking studies were preformed to all of the synthesized compounds to predict, in a qualitative way, the anticonvulsant activity of the proposed compounds. There is a promising correlation between the results of molecular modeling and the anticonvulsant activity of the synthesized compounds. The highest fitting value was noticed for compounds 9 and 10 , which showed the highest anticonvulsant activity.     

Synthesis and antioxidant activity of novel 15‐alkyl/aryl‐13, 17‐dihydro‐15λ5‐dibenzo [e,k] [1, 3, 7, 10, 2] dioxadiazaphosphacyclotridecin‐15‐selones/thiones/ones

A new class of phosphorus macrocycles were synthesized from 2‐[(E)‐2‐2 [(hydroxymethyl) phenyl] imino ethylidene) amino] phenyl methanol 1 with various phenylphosphorodichloridates, phenyldichlorophosphine, and ethyldichlorophosphite in the presence of triethylamine at 0–10°C under N₂ atmosphere in THF. All the title compounds were confirmed by analytical and spectral data (IR, ¹H‐, ¹³C‐, ³¹P‐NMR, and mass). The title compounds exhibited promising anti‐oxidant activity. J. Heterocyclic Chem., (2011).     

Synthesis and antimicrobialactivity of 2‐alkylcarbamato‐2,3‐dihydro‐5‐propylthio‐1H‐1,3,2‐benzodiazaphosphole 2‐oxides

Novel 2‐alkylcarbamato/thiocarbama‐to‐2,3‐dihydro‐5‐propylthio‐1H‐1,3,2‐benzodiazaphos‐phole 2‐oxides ( 4a–J ) were synthesized by cyclization of 4‐propylthio‐1,2‐phenylenediamine ( 3 ) with the corresponding dichlorophosphoryl carbamates/thiocarbamates ( 2a–J ) that were obtained by the addition of alcohols/thiols to isocyanatophosphoryl dichloride ( 1 ). The structures of the title compounds were confirmed by the ¹H, ¹³C, ³¹P NMR, and mass spectral studies. Some of these products were found to possess significant antimicrobial activity. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:336–340, 2000     

4‐Nitro‐3‐(5‐tetrazole)furoxan and Its Salts: Synthesis,Characterization, and Energetic Properties

A series of new energetic salts based on 4‐nitro‐3‐(5‐tetrazole)furoxan (HTNF) has been synthesized. All of the salts have been fully characterized by nuclear magnetic resonance (¹H and ¹³C), infrared (IR) spectroscopy, elemental analysis, and differential scanning calorimetry (DSC). The crystal structures of neutral HTNF ( 3 ) and its ammonium ( 4 ) and N‐carbamoylguanidinium salts ( 9 ) have been determined by single‐crystal X‐ray diffraction analysis. The densities of 3 and its nine salts were found to range from 1.63 to 1.84 g cm^?3. Impact sensitivities have been determined by hammer tests, and the results ranged from 2 J (very sensitive) to >40 J (insensitive). Theoretical performance calculations (Gaussian 03 and EXPLO 5.05) provided detonation pressures and velocities for the ionic compounds 4 – 12 in the ranges 25.5–36.2 GPa and 7934–8919 m s^?1, respectively, which make them competitive energetic materials.     

Synthesis of New Metal‐Free 1,4,8,11‐Tetraaza[14]annulene Derivatives Using 2‐Heteroaryl‐substituted Trimethinium Salts

The reaction of 2‐heteroaryl‐substituted trimethinium salts (A, B, and C) with aromatic 1,2‐diamines ( a , b , c , d , and e ) in acetonitrile/acetic acid leads to 6,13‐disubstituted 1,4,8,11‐tetraaza[14]annulene derivatives ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ). The UV–vis spectral behavior of these compounds was examined in acetonitrile. Elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and mass spectra confirm the molecular structure of the newly synthesized compounds.     

Design,Synthesis, and Insecticidal Activity of 1,5‐Diphenyl‐1‐pentanone Analogues

Three series of novel 1,5‐diphenyl‐1‐pentanone derivatives were designed and synthesized. Their structures were characterized by IR, ¹H NMR techniques, and elemental analysis. The insecticidal activities of the new compounds were preliminarily evaluated. The bioassay results indicated that the compounds X11 – X30 displayed better aphicidal activity against Aphis gossypii than compounds X1 – X10 and the lead compound (E)‐1,5‐diphenyl‐1‐penten‐1‐one ( A ). The inhibitory rates of compounds X6 and X29 were 100% against Plutella xylostella (L.) at 600 mg·L^?1. Compounds X12 , X13, X19 , X24, X25 , X26 and X27 showed higher insecticidal activity against Tetranychus cinnabarinus (Boisduval) at 600 mg·L^?1 than the lead compound ( A ).     

Design,synthesis of (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐ substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐dione analogues as potential cytotoxic agents

In an attempt to achieve promising cytotoxic agents, a series of new (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐diones 10 a‐n were designed, synthesized, and characterized by ¹H NMR, ¹³C NMR, IR, and ESI‐MS techniques. These compounds synthesized from appropriate reaction procedures with better yields. All the novel synthesized compounds 10a‐n were evaluated for their cytotoxic activity against the MCF‐7 cell line (Human breast cancer cell line) at different concentrations of 0.625, 1.25, 2.5, 5, and 10 μM, respectively. The cytotoxic evaluation assay is presented in terms of IC₅₀ values and percentage cell viability reduction compared against standard drug cisplatin. Among all novel synthesized compounds 10a‐n , some of the representative analogues particularly 10g and 10e exhibit remarkable cytotoxic activity with IC₅₀ values 0.454 and 0.586 μM, comparable to that of the standard drug cisplatin, and some analogues 10d , 10f , 10k, and 10m also have shown significant activity.     

Synthesis and antimicrobial activity of some 7‐aryl‐5,6‐dihydro‐14‐aza[1]benzopyrano[3,4‐b]phenanthren‐8H‐ones

The title compounds, 7‐aryl‐5,6‐dihydro‐14‐aza[1]benzopyrano[3,4‐b]phenanthren‐8H‐ones 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , 3l have been synthesized by reacting various 4‐hydroxy coumarins 1a , 1b , 1c with 2‐arylidene‐1‐tetralones 2a , 2b , 2c , 2d in the presence of ammonium acetate and acetic acid under Krohnke's reaction condition. The structures of all the synthesized compounds were supported by analytical, IR, ¹H‐NMR, and ¹³C‐NMR data. All the synthesized compounds 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , 3l have been screened for their antibacterial activities against Escherichia coli (Gram ?ve bacteria), Bacillus subtilis (Gram +ve bacteria), and antifungal activity against Candida albicans (Fungi). J. Heterocyclic Chem., (2011).     

A Facile and Simple Synthesis of Novel 2‐(substituted)‐5‐(1‐methyl‐1H‐indazol‐3‐yl)‐Oxazole Derivatives

Novel 2‐(substituted)‐5‐(1‐methyl‐1H‐indazol‐3‐yl)‐oxazoles ( 13 ) were synthesized in moderate yields, from 1‐methyl‐1H‐Indazole 3‐carboxylic acid ( 1 ), by converting it into a variety of amides ( 12 ) and further its heterocyclization. The structures of all the compounds have been elucidated on the basis of IR, ¹H‐NMR, and HRMS.     

Synthesis of 1‐substituted 5‐aryl‐3‐(3‐coumarinyl)‐2‐pyrazolines by the reaction of 3‐aryl‐1‐(3‐coumarinyl)propen‐1‐ones with hydrazines

1‐Acetyl‐ and 1‐propionyl‐2‐pyrazolines 11‐27 have been synthesized by the reaction of (3‐coumarinyl)chalcones 1‐10 with hydrazine in hot acetic acid or propionic acid. While 5‐aryl‐3‐(3‐coumarinyl)‐1‐phenyl‐2‐pyrazolines 28‐35 have been prepared by the reaction of (3‐coumarinyl)chalcones 1,3,5‐10 with phenylhydrazine in hot pyridine. Structures of all new compounds have been elucidated by microanalyses, ¹H and ¹³C nmr spectroscopies.     

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 of 10‐amino‐9‐aryl‐2,3,4,5,6,7,9,10‐octahydroacridine‐1,8‐dione derivatives

A series of novel 10‐amino‐9‐aryl‐2,3,4,5,6,7,9,10‐octahydroacridine‐1,8‐dione derivatives 4 were synthesized by hydrazine or phenylhydrazine and 9‐aryl‐1,8‐dioxo‐2,3,4,5,6,7,9‐heptahydroxanthene derivatives 3 , which were prepared by 5‐substituted‐1,3‐cyclohexanedione 1 and aromatic aldehydes 2 in the presence of concentrated H₂SO₄ as a catalyst in water. The structures of all compounds were characterized by IR, MS, ¹H‐NMR, and elemental analysis, and the title compounds possess good fluorescence properties. J. Heterocyclic Chem., (2012).     

Efficient Synthesis of Pyrrolo [2,3‐d] Pyrimidines Containing 1,4‐Disubstituted‐1,2,3‐Triazole Derivatives

Here, we demonstrate a simple but highly efficient method for the synthesis of multifunctionalized pyrrolo[2,3‐d]pyrimidines containing 1,4‐disubstituted 1,2,3‐triazole derivative coupled with various amines ( 10a , 10b , 10c , 10d , 10e , 10f , 10g ) and alcohol ( 10h ) to obtain final compounds ( 11a , 11b , 11c , 11d , 11e , 11f , 11g , 11h ) with reasonable to excellent yields (25% to 94%). The newly synthesized compounds were characterized by IR, ¹HNMR, ¹³CNMR, and mass spectroscopy analysis.     

Synthesis of 15‐Cyano‐12‐oxopentadecano‐15‐lactone and 15‐Cyano‐ 12‐oxopentadecano‐15‐lactam

15‐Cyano‐12‐oxopentadecano‐15‐lactone was synthesized in 59% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by reaction with trimethylsilylcyanide, hydrolysis, ring‐expansion, and Nef reaction. A two‐step, one‐pot synthesis of intermediate 2‐hydroxy‐4‐(1‐nitro‐2‐oxycyclododecyl)butanenitrile from 3‐(1‐nitro‐2‐oxocyclododecyl)propanal was developed and the conditions for the Nef reaction were studied. 15‐Cyano‐12‐oxopentadecano‐15‐lactam was synthesized in 40% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by Strecker reaction, ring‐expansion, and Nef reaction. The conditions for the Strecker and Nef reactions were studied. The structures of the target compounds, intermediates, and by‐product were characterized by IR, ¹H‐ and ¹³C‐NMR, and elemental analysis or MS.     

Synthesis and Reactions of Some Heterocyclic Candidates Based on 2‐Amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene Moiety as Anti‐Arrhythmic Agents

In continuation of our previous work, a series of novel thiophene derivatives 4 , 5 , 6 , 8 , 9 , 9a , 9b , 9c , 9d , 9e , 10 , 10a , 10b , 10c , 10d , 10e , 11 , 12 , 13 , 14 , 15 , 16 were synthesized by the reaction of ethyl 2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carboxylate ( 1 ) or 2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carbonitrile ( 2 ) with different organic reagents. Fusion of 1 with ethylcyanoacetate or maleic anhydride afforded the corresponding thienooxazinone derivative 4 and N‐thienylmalimide derivative 5 , respectively. Acylation of 1 with chloroacetylchloride afforded the amide 6 , which was cyclized with ammonium thiocyanate to give the corresponding N‐theinylthiazole derivative 8 . On the other hand, reaction of 1 with substituted aroylisothiocyanate derivatives gave the corresponding thiourea derivatives 9a , 9b , 9c , 9d , 9e , which were cyclized by the action of sodium ethoxide to afford the corresponding N‐substituted thiopyrimidine derivatives 10a , 10b , 10c , 10d , 10e . Condensation of 2 with acid anhydrides in refluxing acetic acid afforded the corresponding imide carbonitrile derivatives 11 , 12 , 13 . Similarly, condensation of 1 with the previous acid anhydride yielded the corresponding imide ethyl ester derivatives 14 , 15 , 16 , respectively. The structures of newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, MS spectral data, and elemental analysis. The detailed synthesis, spectroscopic data, LD₅₀, and pharmacological activities of the synthesized compounds are reported.     

A Facile and Efficient Synthesis of 2‐(5‐(4‐Substitutedphenyl)‐4, 5‐dihydro‐3‐phenylpyrazol‐1‐yl)‐6‐Substitutedbenzothiazoles and Their Biological Studies

A series of new 1‐substituted 3, 5‐diarylpyrazolines ( 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ) were synthesized in good yield by both conventional and microwave‐assisted synthesis from α, β‐ unsaturated ketones ( 6 , 7 , 8 , 9 ) in n‐butanol and benzothiazole hydrazines ( 2 , 3 , 4 , 5 ). All the new compounds were characterized by IR, NMR, and mass spectral data. The synthesized compounds ( 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ) were evaluated for antibacterial and anthelmintic activities. The compounds showed potent anthelmintic activity against earthworm species (Eudrilus eugeniae) and moderate antibacterial activity against bacterial strains such as Gram positive bacteria, Enterococcus faecalis, Staphylococcus aureus, and Bacillus subtilis, and Gram negative bacteria, Escherichia coli and Proteus mirabilis.     

Investigation of Some Functionalization Reactions of 4‐Benzoyl‐5‐phenyl‐1‐(4‐methoxyphenyl)‐1H‐pyrazole‐3‐carbonyl Chloride and Their Antimicrobial Activity

The 1H‐pyrazole‐3‐carboxylic acid 1 was converted via reactions of its acid chloride 3 with various asymmetrical disubstituted urea and alcohol derivatives into the corresponding novel 4‐benzoyl‐N‐(N′,N′‐dialkylcarbamyl)‐1‐(4‐methoxyphenyl)‐5‐phenyl‐1H‐pyrazole‐3‐carboxamide 4a , b and alkyl 4‐benzoyl‐1‐(4‐methoxyphenyl)‐5‐phenyl‐1H‐pyrazole‐3‐carboxylate 7a‐c , respectively, in good yields (57%‐78%). Friedel‐Crafts reactions of 3 with aromatic compouns for 15 min.‐2 h led to the formation of the 4‐3‐diaroyl‐1‐(4‐hydroxyphenyl)‐5‐phenyl‐1H‐pyrazoles 9a‐c , 4‐benzoyl‐1‐(4‐methoxyphenyl)‐3‐aroyl‐5‐phenyl‐1H‐pyrazoles 10a , b and than from the acylation reactions of 9a‐c were obtained the 3,4‐diaroyl‐1‐(4‐acyloxyphenyl)‐5‐phenyl‐1H‐pyrazoles 13a‐d . The structures of all new synthesized compounds were established by NMR experiments such as ¹H, and ¹³C, as well as 2D COSY and IR spectroscopic data, and elemental analyses. All the compounds were evaluated for their antimicrobial activities (agar diffusion method) against eight bacteria and two yeasts.     

Synthesis and pharmacological properties of N‐substituted‐N′‐(4,6‐dimethylpyrimidin‐2‐yl)‐thiourea derivatives and related fused heterocyclic compounds

A series of new N‐Substituted‐N′‐(4,6‐dimethylpyrimidin‐2‐yl)‐thiourea derivatives ( 3a , 3b , 3c , 3d ) and related fused heterocyclic compounds ( 4a , 4b , 4c , 4d ) were synthesized using tetrabutylammonium bromide as phase transfer catalyst (PTC). N‐[(2E)‐5,7‐dimethyl‐2H‐[1,2,4] thiadiazolo [2,3‐a] pyrimidin‐2‐ylidene] derivatives ( 4a , 4b , 4c , 4d ) were prepared by oxidative cyclization of 3a , 3b , 3c , 3d . The structures of these novel compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectrometry, and the elemental analysis. The crystal structures were determined from single crystal X‐ray diffraction data. The results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms and showed higher activity against fungi than bacteria. Compounds 3d and 3a exhibited the greatest antimicrobial activity. J. Heterocyclic Chem., 2011.     

Synthesis and antimicrobial activities of new 4,6‐diaryl‐ 4,5‐dihydro‐3‐hydroxy‐2H‐indazoles

A series of new 4,6‐diaryl‐4,5‐dihydro‐3‐hydroxy‐2H‐indazoles 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k were synthesized by the cyclization of ethyl 2‐oxo‐4,6‐diarylcyclohex‐3‐ene carboxylates 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k . The compounds were characterized by IR, ¹H NMR, ¹³C NMR, 2D NMR, and elemental analysis. The synthesized compounds were evaluated for in vitro antibacterial and antifungal activities against Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Candida albicans, Aspergillus niger, Aspergillus flavus, and Rhizopus sp. Most of the compounds exhibited good activity against the tested organisms. J. Heterocyclic Chem.,, (2012).     

Synthesis,Characterization, and Herbicidal Activities of New 1,3,4‐Oxadiazoles, 1,3,4‐Thiadiazoles,and 1,2,4‐Triazoles Derivatives Bearing (R)‐5‐Chloro‐3‐fluoro‐2‐phenoxypyridine

Synthesis of some novel 1,2,4‐triazoles, 1,3,4‐oxadiazoles and 1,3,4‐thiadiazoles bearing a (R) 5‐(1‐(4‐(5‐chloro‐3‐fluoropyridin‐2‐yloxy)phenoxy)ethyl) unit, as a moiety of commercial herbicide, using their thiosemicarbazides in an alkaline, iodine and acidic media is reported, respectively. The structure of the synthesized compounds was characterized by IR, ¹H, ¹³C NMR spectroscopic data, and elemental analyses. The herbicidal activities of synthesized compounds were evaluated against Echinochloa cruss‐galli, Avena fatua, and Sorgum halepense weeds. Compounds 7 and 12a showed potential herbicidal activity against gramineous weeds. Our results may provide some guidance for synthesis development of some novel oxa or thiadiazole and triazole‐based herbicidal lead structures.