- Synthesis, spectral, magnetic, DFT calculations, antimicrobial studies and phenoxazinone synthase biomimetic catalytic activity of new binary and ternary Cu(II), Ni(II) and Co(II) complexes of a tridentate ONO hydrazone ligand
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New mononuclear copper(II), nickel(II) and cobalt(II) hydrazone complexes of 2-cyano-N′-((4-oxo-4H-chromen-3-yl)methylene)acetohydrazide have been synthesized. Structure identification of the prepared complexes was carried out by physicochemical and spectroscopic techniques including elemental analyses, infrared, electronic, mass and electron spin resonance spectra, thermal analysis, conductivity and magnetic susceptibility measurements, powder x-ray diffraction and transmission electron microscope. The isolated binary complexes are neutral mononuclear complexes (with 1:1 and 1:2; M:L stoichiometries) and ternary complexes (with 1:1:1; M:L:L′ stoichiometry). The analytical and spectroscopic techniques illustrated the monoanionic tridentate behavior of the hydrazone ligand with γ-pyrone oxygen, enolic oxygen and azomethine nitrogen coordinating sites. The metal complexes displayed square planar, tetrahedral and octahedral geometries. Density Functional Theory calculations were carried out for the chelating agent and its copper(II) chelates. The phenoxazinone synthase activity of the binary copper(II) complexes was studied and discussed. The antimicrobial activity of the hydrazone ligand and its complexes was evaluated toward some sorts of Gram–positive bacteria, Gram–negative bacteria, yeast and fungus.
- Shebl, Magdy,Saleh, Akila A.,Khalil, Saied M. E.,Dawy, Magdah,Ali, Amira A. M.
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- Green Synthesis of Pyrazole and Oxazole Derivatives
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New intermediate 3-methyl-5-oxopyrazol propanenitrile was synthesized by one pot three component reactions using ethyl cyanoacetate, hydrazine hydrate, and ethyl acetoacetate and was used for the synthesis of new oxazole and pyrazole derivatives. All reactions were carried out using eco-friendly solvents and without catalyst.
- Toche, Raghunath B.,Patil, Vasant M.,Chaudhari (Patil), Sunita A.,Chavan, Satish M.,Sabnis, Ram W.
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- Ring-chain transformation of 4-aroyl-5-phenylamino-2,3-dihydrothiophene-2,3-diones: Facile and efficient synthesis of novel pyrrolo[2,3-c]pyrazol-3(2H)-ones and 1,2-dihydro-5H,6H-pyridazine-5,6-diones
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Seven, novel pyrrolo[2,3-c]pyrazol-3(2H)-one and 1,2-dihydro-5H,6H-pyridazine-5,6-dione chromophores were synthesized by the reaction of 4-aroyl-5-phenylamino-2,3-dihydrothiophene-2,3-diones with cyanoacetohydrazide and arylhydrazines such as phenylhydrazine and 4-nitrophenylhydrazine. These derivatives were characterized by elemental analysis, IR, UV-Visible, 1H, 13C NMR and mass spectroscopy. Spectral characteristics of the compounds were studied in four organic solvents of differing polarity.
- Hafez Taghva, Pardis,Kabirifard, Hassan
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- Synthesis, characterization and DNA photocleavage study of a novel dehydroacetic acid based hydrazone Schiff's base and its metal complexes
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A series of some novel colored complexes of Co(II), Ni(II), Cu(II), Mn(II) and Zn(II) with a novel dehydroacetic acid based hydrazone Schiff's base has been synthesized and evaluated for their DNA photocleavage potential. The ligand utilized in the present investigation was synthesized via a condensation reaction between cyanoacetic acid hydrazide and dehydroacetic acid. Further, the ligand was treated with different metal acetates of first transition series in 1:1 and 1:2 (metal to ligand) ratios, respectively, to obtain metal complexes with different ligand to metal stoichiometry. Ligand as well as all the synthesized metal complexes were characterized on the basis of data obtained from the techniques like 1H and 13C NMR, IR spectroscopy, mass spectrometry, UV visible spectroscopy, elemental analysis and molar conductance. 1H NMR spectrum of Zn(II) complexes showed the coordination of enolic oxygen atom without deprotonation, but in case of DLCu, the deprotonation of enolic proton was occurred prior to coordination. IR data revealed the participation of a carbonyl oxygen atom of ligand in coordination with metal ions. UV visible data confirmed the square-planar and octahedral geometry of the complexes. Mass spectrum showed the formation of both 1:1 and 1:2 metals to ligand stoichiometry. Most of metal complexes exhibited very good DNA photocleavage activities.
- Pal,Kumar,Gupta,Beniwal
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- Multifunctional iminochromene-2H-carboxamide derivatives containing different aminomethylene triazole with BACE1 inhibitory, neuroprotective and metal chelating properties targeting Alzheimer's disease
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Alzheimer's disease (AD) is a neurodegenerative disorder known for the presence of amyloid beta plaques resulting from the sequential action of β-secretase and γ-secretase on amyloid precursor protein. We developed and synthesized, through click reactions, a new family of iminochromene carboxamides containing different aminomethylene triazole. The BACE1 inhibition, neuroprotective capacity and metal chelation of these derivatives make them ideal candidates against AD. Most of the synthesized compounds were shown to have potent BACE1 inhibitory activity in a FRET assay, with an IC50 value of 2.2 μM for the most potent compound. Moreover, molecular modeling evaluation of these BACE1 inhibitors demonstrates the vital role of the amine and amide linkers through hydrogen bond interactions with key amino acids in the BACE1 active site. Our in vitro neuroprotective evaluations in PC12 neuronal cells of Aβ-induced neuroprotection demonstrated promising activity for most of the compounds as neuroprotective agents. Based on our findings, we propose that introduction of a phthalimide substitute on the triazole ring shown to be interesting multifunctional lead compound worthy of further study.
- Iraji, Aida,Firuzi, Omidreza,Khoshneviszadeh, Mehdi,Tavakkoli, Marjan,Mahdavi, Mohammad,Nadri, Hamid,Edraki, Najmeh,Miri, Ramin
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- Synthesis of Diphenyl Pyridazinone-based flexible system for conformational studies through weak noncovalent interactions: Application in DNA binding
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This paper reports conformational studies of pyridazinone-based flexible dimer connected through diethylamine linker. The conformational studies have been done by X-ray crystal structure and DFT calculation. Further, after crystallization, the compound has shown two types of crystals, one is hydrated and another one is non-hydrated. The hydrated and non-hydrated crystals showed difference in their conformation due to the presence of water in crystal lattice of hydrated crystal. The difference in their conformation has been proved by crystallographic studies, DSC curves and detailed analysis of Hirshfeld surfaces and fingerprint plots facilitating a comparison of intermolecular interactions. Along with conformational studies, this compound also showed DNA binding, as revealed in docking simulation studies.
- Kumar, Ranjeet,Singh, Praveen,Gaurav, Archana,Yadav, Pratima,Khanna, Ranjana S.,Tewari, Ashish Kumar
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- A new modification of the Friedlaender synthesis. A simple route to 2-aminoquinoline-3-carboxylic acid and its derivatives
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A new version of the Friedlaender synthesis of 2-aminoquinoline-3- carboxylic acid and its derivatives from stable 2-tosylaminobenzaldehyde or its morpholinal was proposed.
- Ukhin,Belov
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- 2-Imino 2H-chromene and 2-(phenylimino) 2H-chromene 3-aryl carboxamide derivatives as novel cytotoxic agents: synthesis, biological assay, and molecular docking study
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The inhibition of AKR1B10 has been recognized as a potential therapeutic approach to the treatment of various types of cancers. A novel series of compounds with imino-2H-chromen and phenylimino-2H-chromen scaffolds were synthesized by Knoevenagel condensation reaction. The in vitro cytotoxic activity of synthesized compounds was evaluated against MOLT-4 and SK-OV-3 cells. Among the tested compounds, N-(3,4-dimethoxyphenyl)-2-(phenylimino)-2H-chromene-3-carboxamide (8g) demonstrated potent inhibitory activity against both examined cell lines. The results of the molecular docking study suggested that this compound is involved in critical hydrogen-bonding interactions with the Val301 and Lue302 of AKR1B10 catalytic site.
- Edraki, Najmeh,Iraji, Aida,Firuzi, Omidreza,Fattahi, Yousef,Mahdavi, Mohammad,Foroumadi, Alireza,Khoshneviszadeh, Mehdi,Shafiee, Abbas,Miri, Ramin
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- Spectroscopic characterization of Cu(II), Ni(II), Co(II) complexes, and nano copper complex bearing a new S, O, N-donor chelating ligand. 3D modeling studies, antimicrobial, antitumor, and catalytic activities
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A new tridentate hydrazone ligand (HL), its Co(II), Ni(II), Cu(II) complexes (in 1:1, 1:2 molar ratios of metal to ligand), and the mixed-ligand Co(II), Ni(II), Cu(II) complexes of the ligand HL, with 8-HQ in 1:1:1 (M:L:8-HQ) stoichiometry, in addition to a nano Cu(II) complex have been synthesized and characterized using physical, analytical and spectral methods. Octahedral geometry was assigned for all investigated complexes except Cu(II) complex 1 which exhibited square planar arrangement. The TGA results suggested the thermal stability of the current complexes. The XRD data indicated that the particles of Cu(II) complex 2 were situated in nano-scale range. Furthemore, the SEM and TEM images of the nano Cu(II) complex 2 showed spherical and sheet-shaped particles with an average size of 48 nm. The geometries of the metal complexes were optimized with respect to the energy taking the 6-311G(p,d) basis set in Gaussian 09 W program in gaseous phase by DFT. The data obtained revealed that all metal complexes are more reactive than the free ligand HL, and the Cu(II) complex 1 has the highest chemical reactivity. The antimicrobial activity study illustrated enhancement in activity of the free ligand upon complex formation., and the Cu(II) complex 1 may be considered as promising antibacterial agent, and as promising antifungal agent. The results of antitumor activity study revealed an inhibition of HepG-2 cell growth for the ligand HL, with enhancement in activity upon complexation, and the Cu(II) complex 1 exhibited the highest cytotoxic activity. The phenoxazinone synthase activity study indicated the ability of both Cu(II) complexes 1 and 2 to catalyze the oxidative dehydrogenation of 2-aminophenol (OAPH) to 2-aminophenoxazine-3-one (APX) under atmospheric conditions and at room temperature.
- Ali, Amira A. M.,Dawy, Magdah,El-ghamry, Mosad A.,Khalil, Saied M. E.,Saleh, Akila A.,Shebl, Magdy
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- AIE based “on-off” fluorescence probe for the detection of Cu2+ ions in aqueous media
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A simple hydrazine carboxamide derivative with intramolecular charge transfer and aggregation induced emission (AIE) properties have been designed and synthesized. The derivative (Probe 1) shows typical AIE characteristic emission in THF-water mixtures and emits yellowish orange color on reaching the water fraction 98%. The probe molecule show selective sensing response for Cu2+ ions via fluorescence turn-off mechanism in aqueous media over other metal ions. The emission changes towards Cu2+ ions that could be clearly observed by the naked eyes under 365 nm UV lamp promote the probe molecule as a promising candidate for practical utilization. Furthermore, from the fluorescence titration data, the detection limit for Cu2+ ions was found to be 0.44 μM.
- Assiri, Mohammed A.,Al-Sehemi, Abdullah G.,Pannipara, Mehboobali
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- Discovery of SHR1653, a Highly Potent and Selective OTR Antagonist with Improved Blood-Brain Barrier Penetration
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The oxytocin receptor (OTR) plays a major role in the control of male sexual responses. Antagonists of the OTR have been reported to inhibit ejaculation in animal models and serve as a potential treatment for premature ejaculation (PE). Herein, we describe a novel scaffold featuring an aryl substituted 3-azabicyclo [3.1.0] hexane structure. The lead compound, SHR1653, was shown to be a highly potent OTR antagonist, which exhibited excellent selectivity over V1AR, V1BR, and V2R. This novel molecule was shown to have a favorable pharmacokinetic profile across species, as well as robust in vivo efficacy in a rat uterine contraction model. Interestingly, SHR1653 exhibited excellent blood-brain barrier penetration, which might be beneficial for the treatment of CNS-related PE.
- Li, Xin,Zhang, Zhigao,Chen, Yang,Wan, Hong,Sun, Jiakang,Wang, Bin,Feng, Bingqiang,Hu, Bing,Shi, Xingxing,Feng, Jun,Zhang, Lei,He, Feng,Bai, Chang,Zhang, Lianshan,Tao, Weikang
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supporting information
p. 996 - 1001
(2019/06/21)
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- A three component one-pot synthesis of N-amino-2-pyridone derivatives catalyzed by KF-Al2O3
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Synthesis of 1,6-diamino-4-phenyl-3,5-dicyano-2-pyridone derivatives via a one-pot, three-component reaction of aryl aldehydes, malononitrile, and cyanoacetic hydrazide at room temperature using KF-Al2O3 as a recyclable catalyst have been developed. The reaction proceeds through the initial Knoevenagel condensation between aldehyde and malononitrile in the presence of KF-Al2O3 to form the benzylidene derivative which then undergoes Michael addition with cyanoacetic hydrazide followed by intramolecular cyclization of the resulting intermediate to produce the N-amino-2-pyridones in good to excellent yields. The structure of the synthesized compounds were characterized and established on the basis of their spectral data analysis and single-crystal XRD analysis.
- Kshiar,Shangpliang,Myrboh
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supporting information
p. 1816 - 1827
(2018/06/25)
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- Facile one-pot synthesis of new [1,2,4]triazolo[1,5-a]pyridine derivatives by ultrasonic irradiation
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Herein, we report an ultrasonic promoted facile and convenient “one-pot” procedure for the synthesis of new [1,2,4]triazolo[1,5-a]pyridine derivatives 3, 4 and 5, using Amberlite IRA-400, in short reaction times and high yields and its comparison with classical reaction conditions. The structures of new compounds were assigned with the help of analytical 1H, 13C NMR, and mass spectral studies.
- Zribi, Lazhar,Zribi, Fathi,Marco-Contelles, José,Chabchoub, Fakher,Ismaili, Lhassane
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supporting information
p. 1934 - 1939
(2017/10/13)
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- Design, synthesis and anti-acetylcholinesterase evaluation of some new pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives
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The target new hybrid molecule types pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines phosphonates 4 and 2-(coumarin-3’’-yl)-7-phenylpyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines 5 were prepared via Michaelis–Arbuzov rearrangement (Arbuzov reaction) of pyrazolotriazolopyrimidines chloride 3a–c, with trialkyl phosphate and Knoevenagel reaction of 2-cyanomethyl derivatives 3d–f with salicylic aldehyde, respectively. The precursors 3 were obtained in two steps starting from aminopyrazole 1. Target compounds 4 and 5 were completely characterized by 1H NMR, 13C NMR, 31P NMR, IR and HRMS. The anti-acetylcholinesterase activity of compounds 4 and 5 was evaluated, and results found indicated that they have possessed significant activities (IC50?=?1.73–39.86?μM), and the preliminary SAR of these compounds was investigated.
- Romdhane, Anis,Said, Abderrahim Ben,Cherif, Maher,Jannet, Hichem Ben
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p. 1358 - 1368
(2016/07/06)
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- The C=N?C-X σ-hole interaction acts as a conformational lock
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An interesting C=N?C-X conformation lock, which determines the linear alignment of the C=N and C-X fragments, has been found for the first time and is rationalized by density functional theory calculations. Second-order perturbation theory analysis based on the NBO method further reveals that the nature of the C=N?C-X interaction is mainly the lp(C=N) → σ*(C-X) interaction.
- Zhang, Zhenfeng,Wang, Li,Xuan, Xiaopeng
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- A convenient synthesis of new 2-cyanomethylthieno[3,2-e]1[1,2,4]- triazolo[1,5-c]pyrimidine derivatives
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A new series of 2-cyanomethylthienotriazolopyrimidines has been synthesized in good yield through a facile method using substituted aminothiophene-3- carbonitrile as building block and cyanoacetic acid hydrazide as reagent in one framework. The structure of the synthesized compounds was established on the basis of their mass and spectral data.
- Jabli, Dhiab,Dridi, Khaireddine,El Efrit, Mohamed L.
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p. 403 - 408
(2014/05/20)
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- CCSO nano catalyzed solid phase synthesis of 3-oxo-5,6-disubstituted-2,3-dihydropyridazine-4-carbonitrile
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Co-doped Ce0.94Ca0.05Sr0.01O1.94 (CCSO) nano particles have been successfully synthesized by an auto-combustion method and were characterized by XRD, TEM and AFM analyses. The catalytic activity of the nano-catalyst is evaluated by the synthesis of substituted pyridazines from substituted benzil and cyano acetylhydrazide, which have great biological and pharmaceutical interest. Thus, a highly economically efficient one-pot solvent free synthesis of pyridazine was developed, which is promoted by the CCSO nano catalyst. The benefits of the reaction are its very short time (2-4 min) and high yields (90-95%). The method offers a highly convergent, inexpensive, and functionality-tolerable procedure for rapid access to important pyridazine compounds in good yields. This journal is
- Singh, Praveen,Kumar, Ranjeet,Yadav, Brijesh Kumar,Khanna, Ranjana S.,Tewari, Ashish Kumar
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p. 51239 - 51243
(2014/12/11)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Paragraph 0175
(2014/05/24)
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- Phenylimino-2H-chromen-3-carboxamide derivatives as novel small molecule inhibitors of β-secretase (BACE1)
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The inhibition of β secretase (BACE1) is potentially important approach to treatment of Alzheimer disease (AD). A novel series of 4-bromophenyl piperazine derivatives coupled to the phenylimino-2H-chromen-3-carboxamide scaffold were investigated as BACE1 inhibitors in this study. Docking study suggested that the phenyl-imino group of the scaffold establishes favorable π-π stacking interaction with side chain of Phe108 of flap pocket. Some of the docking proposed derivatives were synthesized and evaluated for BACE1 inhibitory activity using a FRET-based assay. High BACE1 inhibitory activities were observed from derivatives containing fused heteroaromtic groups attached through the aliphatic linkage to the N4-piperazine moiety, which may be attributed to the engagement of effective interactions with S1-S′1 sub-pocket residues. Of the most potent compounds, 9e displayed an IC 50 value for BACE1 of 98 nM. Some of these derivatives demonstrated good inhibitory activity on Aβ production in N2a-APPswe cells at 5 and 10 μM. These compounds might be considered as promising BACE1 inhibitory agents that could lower Aβ production in AD.
- Edraki, Najmeh,Firuzi, Omidreza,Foroumadi, Alireza,Miri, Ramin,Madadkar-Sobhani, Armin,Khoshneviszadeh, Mehdi,Shafiee, Abbas
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p. 2396 - 2412
(2013/05/21)
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- Combinatorial synthesis of 3,5-Dimethylene substituted 1,2,4-Triazoles
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Combinatorial cyclizations of imidates and hydrazides with methylene linked R groups, generated from the corresponding nitriles and carboxylic acids, respectively, provided a large library of 3,5-dimethylene substituted 1,2,4- trizoles. 2011 Bentham Science Publishers Ltd.
- Woodard, Scott S.,Jerome, Kevin D.
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experimental part
p. 132 - 137
(2012/04/18)
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- Synthesis and antimicrobial activity of pyridopyrazole and pyrazolo[3,4-d]dihydrothiazole
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6-Methyl-1,3-dihydro-4H,7H-pyrazolo[2,3-c]pyridine-4-one (4) were synthesized by microwave as well as conventional method. The reaction time reduced 10 times than that of conventional method. The pyrazolo[3,4-d] dihydrothiazole (8) were synthesized by reacting phenylisothiocyanate with 1-carbethoxy-5-amino-pyrazol-4-ene-3-one and were screened for their antimicrobial activities.
- Deshmukh,Deshmukh,Jagtap,Suryavanshi,Jadhav,Anbhule
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experimental part
p. 613 - 616
(2010/07/08)
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- Novel route for the transformation of a pyrimidine ring using hydrazides
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It has been shown from X-ray structural analytical data that the reaction of 2-ethoxycarbonylmethyl-1,4,6-trimethylpyrimidinium iodide with carboxylic acid hydrazides gives pyrazolo[1,5-a]pyrimidine derivatives and not the isomeric triazolo[4,3-a]pyridines previously reported. This novel and previously unreported rearrangement of 1,2-dialkylpyrimidinium salts occurs via recyclization of the pyrimidine ring with inclusion of a fragment of the nucleophilic reagent into the transformation product. 2006 Springer Science+Business Media, Inc.
- Danagulyan,Tadevosyan,Tamazyan,Panosyan
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p. 233 - 245
(2007/10/03)
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- Rapid microwave-assisted solution phase synthesis of substituted 2-pyridone libraries
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2-Pyridone and 2-quinolone analogues are well-known biologically active heterocyclic scaffolds. Libraries of 3,5,6-substituted 2-pyridone derivatives are generated by rapid microwave assisted solution phase methods using a one-pot, two-step protocol. The three-component condensation of CH-acidic carbonyl compounds, N,N-dimethylformamide dimethylacetal and methylene active nitriles, leads to 2-pyridones and fused analogues in moderate to good overall yields and high purities. The proposed mechanism of this novel multi-component reaction, structure elucidation of products and intermediates are discussed.
- Gorobets, Nikolay Yu.,Yousefi, Behrooz H.,Belaj, Ferdinand,Kappe, C. Oliver
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p. 8633 - 8644
(2007/10/03)
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- Pyrolysis of amino nitriles, cyanohydrazones, and cyanoacetamides. Part I. Elimination reaction of 1-arylmethyleneamino-1,2-dihydro-4, 6-dimethyl-2-oxopyridine-3-carbonitriles and substituted benzaldehyde cyanoacetylhydrazones
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Pyrolysis of the Schiff bases of 1-arylmethyleneamino-1,2-dihydro-4, 6-dimethyl-2-oxopyridine-3-carbonitriles (1-5) has been studied. These compounds eliminate via a six-membered transition state to produce substituted benzonitriles and 2-hydroxy-4,6-dimethylpyridine-3-carbonitrile. These eliminations are unimolecular first-order reactions. The kinetic data gave a good correlation with σ0 values of the substituents on the aryl group with ρ = 0.83 at 520 K. Utilization of the pyrolytic reaction in synthesis of various benzonitriles is considered, and mechanistic information has been obtained by comparing the kinetic data and product analysis of the Schiff bases with their open-chain substituted benzaldehyde cyanoacetylhydrazones (6-9) analogues.
- Al-Awadi,Elnagdi,Mathew,El-Gamry,Abdel Khalik
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p. 741 - 748
(2007/10/03)
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- Antihypertensive actions of hydrazidones: Study of acylated dichloroarylhydrazones
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A series of acylated dichloroarylhydrazones has been prepared and evaluated on spontaneously hypertensive rats (SHR). The presence of 2-Cl and 6-Cl aromatic substituents in a clonidine like position is not required since derivatives bearing 2- and 4-chloro as well as 3- and 4-chloro substituents exert antihypertensive activities. Activity is also maintained in certain 2,6 disubstituted derivatives where one of the chlorine atoms is replaced by F or NO2.
- Cave,Galons,Miocque,Rinjard,Tran,Binet
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- Constitution and Redox Stability of Copper(II)-Complexes with Substituted Hydrazines
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CuCl2 reacts with substituted hydrazines forming chelates of the Cu(II)L2Cl2 type (L = RCONHNH2, RCONHN(C6H5)2, RCONHNHCOR, H2NNHCO(CH2)nCONHNH2) which are characterized by quantitative analysis, i.r. and e.p.r. spectra.The complex polyhedron exhibits the geometry of a tetragonally distorted octahedron of C2v symmetry.The complexes undergo intramolecular redox decomposition in acetonitril forming Cu(I) species.The rate constants increase with decreasing half wave oxydation potential and decreasing HOMO energy of the hydrazine ligands, respectively.
- Kempe, G.,Boegel, M.,Roewer, G.
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p. 360 - 366
(2007/10/02)
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