1,225 results on '"Diazepine"'
Search Results
2. Protective Effects of a Dihydrodiazepine Against Endotoxin Shock Through Suppression of TLR4/NF-κB/IRF3 Signaling Pathways
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Hanieh, Hamza, Alfwuaires, Manal A., Abduh, Maisa S., Abdrabu, Alyaa, Qinna, Nidal A., and Alzahrani, Abdullah M.
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- 2024
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3. Synthesis, anticancer for prostate cancer cells and antibacterial activity of new diazepine derivatives
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Nahla Ghaze Fahad, Noor H. Imran, Hussein Ali Kadhim Kyhoiesh, and Mohammed K. Al-Hussainawy
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Heterocyclic ,Diazepine ,Anti-cancer ,PC3 ,Antibacterial ,Chemistry ,QD1-999 - Abstract
In the current study, four new benzodiazepine derivatives were synthesized via a reaction of o-phenylenediamine with some chalcone derivatives. The synthesized compounds were characterized by 1H NMR and FT-IR spectroscopies. The antibacterial activity of the obtained diazepines was screened against E. coli, Bacillus subtilis, and Staphylococcus aureus. The results showed that compound 8 had the highest activity toward Bacillus subtilis and Staphylococcus aureus, while compounds 5 and 7 showed the highest activity toward E. coli. To support in vitro studies, docking studies have been performed to determine whether the title compounds (5–8) are inhibitors of the androgen receptor prostate cancer mutant H874Y ligand binding domain bound with testosterone and an AR 20–30 peptide (2Q7K), and the relationship between calculated energies and docking studies has been investigated. Among the synthesized diazepines, compound 5 was subjected to anticancer screening, where its activity against human prostate cancer (PC3) was tested. According to the obtained results, compound 5 has good anticancer activity against PC3.
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- 2023
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4. Phosphorus Pentasulfide in Heterocycle Synthesis
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Kaur, Navjeet and Kaur, Navjeet
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- 2022
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5. 地西泮保护黑色素细胞氧化损伤的作用及机制.
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张锡梅, 瞿琳, 孟朵, 邹坤, and 吕金鹏
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BAX protein , *BCL-2 proteins , *OXIDATIVE stress , *DIAZEPAM , *HYDROGEN peroxide , *VITALITY - Abstract
The oxidative stress model of mouse melanocytes B16F10 was established and the protective effect and mechanism of diazepam on oxidative damage of B16F10 cells were studied. B16F10 cells in good growth state were selected to determine the concentration of hydrogen peroxide and the appropriate dose range of diazepam by MTT method. The protective effect of diazepam on oxidative damage of B16F10 cells was observed by fluorescence detection. Western blot was used to further explore the upstream pathway mechanism of diazepam's protective effect. The experimental results showed that diazepam can significantly reverse cellular oxidative damage, restore cell vitality, increase the expression of anti apoptotic protein Bcl-2 under stress, reduce the level of pro apoptotic protein Bax, and ultimately protect B16F10 cells under oxidative stress. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Survey reaction of 2-amino-N-(aryl) benzimidamides with ninhydrin in different conditions and investigation of reaction mechanism using density functional theory (DFT).
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Darehkordi, Ali, Mohammadi, Marziyeh, Sayyahi, Kobra, Ahmadi, Zahra, Rahmani, Fariba, and Nejadkhorasani, Farzaneh
- Abstract
In this investigation, firstly, 1-(2-amino-phenyl)-N-(aryl) methane diamine derivatives were synthesized by reaction of 2-aminobenzo nitrile with aromatic amines in the presence of aluminum chloride as the catalyst. Then, the reaction of these intermediates with ninhydrin in different conditions was investigated. The reaction between ninhydrin and 2-amino-N'-(aryl) benzimidamide derivatives in water as solvent under reflux conditions resulted in the synthesis of diazepine derivatives. The same results were obtained when the reaction was done in EtOH and in the presence of a few drops of sulfuric acid at room temperature. Also, this reaction was carried out in ethanol as solvent without the presence of sulfuric acid at room temperature which resulted in the synthesis of spiro [indene-2,2ʹ-quinazoline] derivatives. And finally, the reaction was carried out in ethanol as solvent without the presence of sulfuric acid at the reflux conditions which resulted in the synthesis of isoquinolino-quinazoline derivatives. These N-heterocycles compounds are important biologically. Mild reaction conditions, simple procedure and purification and also product diversity with changing conditions are important advantages of this method. Also, to better understanding reaction mechanism on the condensation reactions of 2-amino-N-(aryl) benzimidamides with ninhydrin in different conditions, density functional theory (DFT)-based quantum chemical methods have been applied. Calculated atomic charges suggest that the C-1 (+ 0.54 a.u.) center of ninhydrin is a better electrophile than C-2 (+ 0.42 a.u.) center. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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7. 1,3‐Diazepine Derivatives: Strategies for Synthesis.
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Malki, Yohan, Maillard, Ludovic T., and Masurier, Nicolas
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MOIETIES (Chemistry) - Abstract
The present review describes the methodologies reported for the synthesis of 1,3‐diazepine derivatives. This heterocyclic moiety forms the core structure of many compounds with potent biological activities. Synthetic strategies by ring closure or ring transformation are discussed. [ABSTRACT FROM AUTHOR]
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- 2022
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8. One-step synthesis of 2-Methyl-2,4-Diphenyl-2,3-Dihydro-1H-Benzo[b][1,4]diazepine: Investigating crystal structure, hirshfeld surface analysis and supercapacitor applications.
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Topkaya, Cansu, Hökelek, Tuncer, Aslan, Sema, Göktürk, Tolga, Kıncal, Sultan, Çağlar, Umut, and Güp, Ramazan
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MATERIALS science , *INTERMOLECULAR forces , *CRYSTAL structure , *SURFACE analysis , *SINGLE crystals , *BENZODIAZEPINES - Abstract
• Crystal structure elucidated: monoclinic arrangement with P 21/c space group revealed through single crystal X-ray analysis. • Hydrogen bonding dynamics explored: intramolecular O–H···N interactions between the main molecule and uncoordinated water molecule investigated for stability implications. • Comprehensive Hirshfeld surface analysis conducted: highlighted the significance of H...H and H...C/C...H interactions in shaping crystal packing. • Electrochemical performance assessed: potential utility in supercapacitors examined, shedding light on its energy storage capabilities. • Insightful findings: study contributes to understanding N-heteroaromatic compounds' chemistry, emphasizing potential applications in materials science. This study reports the synthesis, spectroscopic characterization and detailed crystal structure analysis of a benzodiazepine compound, 2-methyl-2,4-diphenyl-2,3-dihydro-1H-benzo[b][1,4]diazepine, synthesized from 1,2-phenylenediamine and acetophenone. The crystal structure, determined via single crystal X-ray analysis, reveals the compound's placement within the monoclinic system with the P 2 1 /c space group. The asymmetric unit comprises the main molecule and an uncoordinated water molecule linked through an intramolecular O–H···N hydrogen bond. The crystal packing is influenced by centrosymmetric dimers formed by uncoordinated water molecules through O–H···N hydrogen bonds, along with weak C–H···π interactions. Hirshfeld surface analysis highlights the significance of H ... H and H ... C/C ... H interactions in the crystal packing, providing insight into the intermolecular forces at play. Supercapacitance performance of the GCPE/L DABA electrode was assessed and specific capacitance value of 17.89 mF g −1 was achieved in a 0.1 M Na 2 SO 4 electrolyte. Long-term stability of the GCPE/L DABA electrode was maintained up to 2000 cycles. This study not only elucidates the structural features of the title compound but also sheds light on its potential utility through an investigation into its electrochemical performance via supercapacitor application. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Formation scheme and some properties of a thiamine-derived pigment, pyrizepine, formed through the Maillard reaction.
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Sachiko Kitayama, Asuka Igoshi, Yuko Shimamura, Kyoko Noda, and Masatsune Murata
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THIAMIN pyrophosphate , *MAILLARD reaction , *LIQUID chromatography-mass spectrometry , *BIOLOGICAL pigments , *PIGMENTS , *NUCLEAR magnetic resonance , *AMES test - Abstract
Recently, a yellow Maillard pigment named pyrizepine was identiied from a heated solution containing thiamine and glucose. Here, we examined the formation scheme of this pigment and some biological properties. The mass spectrometry and nuclear magnetic resonance data of pyrizepine prepared from [6-13C] glucose showed that the carbon at 6-position of glucose was inserted at 2 different positions of pyrizepine. 5-(Aminomethyl)-2-methylpyridin-4-amine (AMPA), a degradation product of thiamine, was detected in the reaction solution. The pigment also formed in the solution containing AMPA in place of thiamine. These results showed that pyrizepine formed from AMPA and C4 fragments derived from glucose. Pyrizepine showed antioxidative activities in the superoxide dismutase, 2,2-diphenyl-1-picrylhydrazyl, and H-ORAC assays. The pigment did not show mutagenicity with the Ames test. A trace amount of the pigment was detected in a pan-fried ground pork sample added glucose using liquid chromatography-tandem mass spectrometry. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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10. Complexation of Benzoannelated Porphyrazines with Zinc(II) and Cobalt(II) Acetates in Pyridine.
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Malyasova, A. S., Smirnova, P. N., and Koifman, O. I.
- Abstract
Complexation of tribenzodiazepinoporphyrazine with Cu(II), Zn(II), and Co(II) acetates has been studied. Cu(II) complex of tribenzodiazepinoporphyrazine forms immediately, therefore Zn(II) and Co(II) acetates have been used as salts. It has been found that the rate of complex formation of tribenzodiazepinoporphyrazine with metal ions in pyridine decreases in the series: Cu(II) > Zn(II) > Co(II), this order agrees well with literature data obtained for tetraazaporphin. When diazepine fragment is replaced by pyrazine one, the rate of porphyrazine complexation with Zn(II) decreases. It is supposed that, in the case of tribenzodiazepinoporphyrazine, the reaction of metal insertion proceeds through formation of outer complex, which favors to the further introduction of zinc(II) ion in coordination center of the macrocycle. The complexation of Zn(II) and Co(II) with studied porphyrazines is characterized by low values of activation energy and entropy, which may indicate the strong solvation of transition state. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Synthesis of new seven membered heterocyclic rings: An easy access to indeno-benzo[1,4]diazepines
- Author
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Raza M. Ghalib, Sayed H. Mehdi, Ali M. Malla, Goran A. Bogdanović, Srecko R. Trifunovic, and Mohd G. Alam
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Synthesis ,Crystal structures ,Ninhydrin ,Diazepine ,Benzoimidazole ,Chemistry ,QD1-999 - Abstract
An easy access has been demonstrated for seven membered diazepines and a six membered quinoxaline. The reaction proceeds rapidly with low-cost and readily available chemicals at mild temperature and provides straight forward access to diazepines and quinoxaline. All final products are new and confirmed by spectral analysis and by single crystal X-ray analysis. Two crystal structures of the diazepines have very similar compositions, exhibit similar conformations where four condensed and coplanar rings are placed in the same orientation to the rest of molecule.
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- 2020
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12. 1,3‐Diazepine: A privileged scaffold in medicinal chemistry.
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Malki, Yohan, Martinez, Jean, and Masurier, Nicolas
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PHARMACEUTICAL chemistry ,ENZYME inhibitors ,DRUG design ,NATURAL products ,MOLECULAR interactions - Abstract
Privileged structures have been widely used as effective templates for drug discovery. While benzo‐1,4‐diazepine constitutes the first historical example of such a structure, the 1,3 analogue is just as rich in terms of applications in medicinal chemistry. The 1,3‐diazepine moiety is present in numerous biological active compounds including natural products, and is used to design compounds displaying a large range of biological activities. It is present in the clinically used anticancer compound pentostatin, in several recent FDA approved β‐lactamase inhibitors (e.g., avibactam) and also in coformycin, a natural product known as a ring‐expanded purine analogue displaying antiviral and anticancer activities. Several other 1,3‐diazepine containing compounds have entered into clinical trials. This heterocyclic structure has been and is still widely used in medicinal chemistry to design enzyme inhibitors, GPCR ligands, and so forth. This review endeavours to highlight the main use of the 1,3‐diazepine scaffold and its derivatives, and their applications in medicinal chemistry, drug design, and therapy. We will focus more particularly on the development of enzyme inhibitors incorporating this scaffold, with a strong emphasis on the molecular interactions involved in the inhibition mechanism. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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13. Synthesis, Characterization and Evaluation Antibacterial Activity of Some Schiff Bases and (1,3-Oxazepine or Diazepine-4,7-Dione)
- Author
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Saad Jasim
- Subjects
schiff bases ,oxazepine ,diazepine ,Science - Abstract
In this study, some of Schiff bases, 1,3-oxazepine-4,7-dione and 1,3-diazepine-4,7-dione compounds derived from terephthalaldehyde and substituted aniline have been prepared, Schiff bases (a1-5) which derived from terephthalaldehyde and substituted aniline have been reacted with maleic anhydride and phthalic anhydride to produce 1,3-oxazepine-4,7-dione compounds (b1-10). 1,3-oxazepine-4,7-dione compounds (b1-10) have been reacted with phenyl hydrazine to produce 1,3-diazepine-4,7-dione compounds (c1-10). The prepared compounds were characterized using physical methods, the precise analysis of elements (C.H.N), infrared (IR) and (1H NMR) spectroscopy. The reactions were monitored by. Thin Layer Chromatography (TLC). The antibacterial activity was evaluated for some of the synthesis compounds.ً.
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- 2019
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14. Vegetable Oil-based Hybrid Submicron Particles Loaded with JMV5038: A Promising Formulation against Melanoma.
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Doufène, Koceïla, Malki, Yohan, Vincent, Laure-Anaïs, Cuq, Pierre, Devoisselle, Jean-Marie, Masurier, Nicolas, and Aubert-Pouëssel, Anne
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VEGETABLE oils , *MELANOMA , *CASTOR oil , *DRUG delivery systems , *VEGETABLES , *MELTING points - Abstract
The aim of this work was to carry out a preformulation study on JMV5038 as a new potent cytotoxic agent, and to develop its formulation within vegetable oil-based hybrid submicron particles (HNP) in order to obtain a versatile dosage form against melanoma. JMV5038 was first characterized through physico-chemical tests and it exhibited high melting point and logP value, an important pH-sensitivity that led to the formation of well-identified degradation products at low pH, as well as a substantial solubility value in silylated castor oil (ICO). Then, JMV5038-loaded HNP were formulated through a thermostabilized emulsion process based on the sol-gel cross-linking of ICO. They showed high loading efficiency and their in vitro release kinetic assessed in a biorelevant PBS/octanol biphasic system showed a constant sustained release over one month. The cytotoxic activity and cytocompatibility of HNP were evaluated on A375 melanoma cells and NIH 3T3 cells, respectively. JMV5038-loaded HNP exhibited a slightly enhanced cytotoxic activity of JMV5038 on melanoma cells while demonstrating their safety on NIH 3T3 cells. In conclusion, JMV5038-loaded HNP proved to be an efficient and safe drug subcutaneous delivery system that will be interesting to evaluate through preclinical studies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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15. Synthesis, Characterization of Diazepine-Bicycles System and Study of their Bio-Behavior.
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ALJAMALI, NAGHAM MAHMOOD and MAHMOOD, RABAB MAHDI UBAID
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BENZODIAZEPINES , *CHEMICAL yield , *ALCOHOLISM , *ANXIETY disorders , *SYNTHETIC marijuana , *SEIZURES (Medicine) , *RING formation (Chemistry) , *ANTIBACTERIAL agents - Abstract
Benzodiazepines have psychotropic, sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxing, and amnesic effects, so they are beneficial for a variety of symptoms such as alcohol dependence, seizures, anxiety disorders, panic, agitation and insomnia., most of them are given orally. The target in this study is synthesis of bicycles from Diazepine by cyclization step in two paths (from reaction of Oxazepine compound with and primary amine, or via reaction of imine compound with phthalamide, or via reaction of Diazepine with other amine by insertion reaction to yield other Diazepine from new type. All prepared compounds investigated by types of instrumental methods like (FT.IR, H.NMR, Mass)-spectrophotometric, other chemical characterization, with evaluation of formatted compounds as antibacterial compounds. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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16. Synthesis, Chalcone and Study of the Biological Activity for Different Heterocyclic Compounds from the Chalcone Derivative.
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AL-Hamidawi, Osama Ali and Al-Rammahi, Faez A.
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CHALCONE ,HETEROCYCLIC compounds ,THIOUREA ,ESCHERICHIA coli ,PYRAZOLES ,HYDRAZINES - Abstract
Copyright of Journals Kufa for Chamical is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2021
17. Synthesis and Characterization of Some Bis-1,3 Oxazepine - 4,7- dione and 1, 3 – Diazepine -4,7- dione Derivatives
- Author
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Saad Salim Jasim
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schiff bases ,oaxzpine ,dione ,diazepine ,Science - Abstract
In this study, some of the new compounds have been synthesized including some of different Schiff bases (1-6) via the reaction of phenyl-1,4-diamine with substituted benzaldehyde in absolute ethanol and converted into derivatives of 1,3-oxazepine-4,7-dione (7-12) via ring closure reaction [2+5] of Schiff bases with maleic anhydride in dry benzene then the 1, 3- oxazepine -4, 7- compounds (7-12) were reacted with phenylhydrazine to produce 1,3-diazepine-4,7-dione (13-18). The prepared compounds were characterized by determination of melting point, FT-IR and UV-Visspectra, and some of the prepared compounds have been characterized by (1H-NMR& C.H.N.) techniques.
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- 2018
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18. Targeting matrix metalloproteinases with novel diazepine substituted cinnamic acid derivatives: design, synthesis, in vitro and in silico studies
- Author
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Dharmender Rathee, Viney Lather, Ajmer Singh Grewal, and Harish Dureja
- Subjects
Targeting ,MMP-2 ,MMP-9 ,Diazepine ,Cinnamic acid ,Molecular docking ,Chemistry ,QD1-999 - Abstract
Abstract Lung cancer is the notable cause of cancer associated deaths worldwide. Recent studies revealed that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs (-2 and -9) play an important part in tumor development and angiogenesis, which suggests that creating potent MMP-2 and -9 inhibitors, should be an important goal in lung cancer therapy. In the present study, an effort has been made to develop new anti-metastatic and anti-invasive agents, wherein a series of novel diazepine substituted cinnamic acid derivatives were designed, synthesized and assayed for their inhibitory activities on MMP-2 and MMP-9. These derivatives were prepared via microwave assisted reaction of tert-butyl (3-cinnamamidopropyl)carbamate derivatives mixed with 2,3-dibromopropanoic acid and potassium carbonate was added to obtain 4-(tert-butoxycarbonyl)-1-cinnamoyl-1,4-diazepane-2-carboxylic acid derivatives. The newly synthesized compounds were characterized by IR, NMR and mass spectroscopy. All the tested compounds showed good to excellent cytotoxic potential against A549 human lung cancer cells. The active compounds displaying good activity were further examined for the inhibitory activity against MMPs (-2 and -9). In addition, the structure and anticancer activity relationship were further supported by in silico docking studies of the active compounds against MMP-2 and MMP-9.
- Published
- 2018
- Full Text
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19. Synthesis of new seven membered heterocyclic rings: An easy access to indeno-benzo[1,4]diazepines.
- Author
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Ghalib, Raza M., Mehdi, Sayed H., Malla, Ali M., Bogdanović, Goran A., Trifunovic, Srecko R., and Alam, Mohd G.
- Abstract
One-pot synthesis Green synthesis Crystal structures Up to 80% yield An easy access has been demonstrated for seven membered diazepines and a six membered quinoxaline. The reaction proceeds rapidly with low-cost and readily available chemicals at mild temperature and provides straight forward access to diazepines and quinoxaline. All final products are new and confirmed by spectral analysis and by single crystal X-ray analysis. Two crystal structures of the diazepines have very similar compositions, exhibit similar conformations where four condensed and coplanar rings are placed in the same orientation to the rest of molecule. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
20. A Facile Synthesis of Polycyclic Pyrimidine Fluorophores via Inter- and Intramolecular Cyclization of Activated 2-Amino-3,6-disubstitued Pyrimidin-4-ones.
- Author
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El-Sayed, H. A., Assy, M. G., Mahmoud, W. M., El-Sheakh, A. A., and Morsy, H. A.
- Subjects
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PYRIMIDINE synthesis , *PYRIMIDINE derivatives , *PYRIMIDINES , *RING formation (Chemistry) , *CARBOXYLIC acids , *ACETOPHENONE derivatives , *FLUOROPHORES - Abstract
An efficient synthesis and fluorescent properties of a new series of fused pyrimidine derivatives are described. Condensation of aminopyrimidine derivative 1 with acetophenone leads to olefinic pyrimidine 2, various addition-cyclization reactions of which give the corresponding bicyclic pyrimidines 4, 6, and 8. Cycloaddition reaction of pyrimidine 1 to benzoyl isothiocyanate gives thiourea derivative 9. Intramolecular cyclization of compound 9 with NaOH or Br2 produces pyrimidine derivatives 10 or 12, respectively. Heteroannulation of pyrimidine 1 with ninhydrin or α-carbonyl carboxylic acid 15 gives the tetracyclic pyrimidine 14 and diazepine derivative 18, respectively. Fluorescence properties of pyrimidine derivatives have been tested. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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21. Ammonium chloride-catalyzed green multicomponent synthesis of dihydropyrazine and tetrahydrodiazepine derivatives "on water".
- Author
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Shaabani, Ahmad, Sepahvand, Heshmatollah, and Ghasemi, Shima
- Abstract
This research describes a simple and efficient one-pot synthetic approach for the preparation of tetrahydrodiazepine and dihydropyrazine (or dihydroquinoxaline) derivatives in high yields in the presence of a substoichiometric amount of ammonium chloride as a green accelerator on water at 50 °C within 1–3 h. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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22. Synthesis of 4-OXO-4H-Chromene Derivative with Fused Benzodiazepine Ring
- Author
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Zemanová Ivana, Potančoková Michaela, and Gašparová Renata
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4-oxo-4H-chromene ,1,2-diaminobenzene ,diazepine ,fused heterocycles ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
6-Acetylbenzo[b]chromeno[2,3-e][1,4]diazepin-13(6H)-one 6 was synthesized by reaction of 4- oxo-4H-chromene-3-carboxaldehyde 1 with 1,2-diaminobenzene 2 followed by cyclisation of formed Schiff base 3 and spontaneous oxidation of dihydrodiazepine 4 by air oxygen. Finally, diazepine 5 was acetylated at N(6) by reaction with acetic anhydride.
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- 2016
- Full Text
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23. Contractions of 1,4-Diazepines to Pyrroles Triggered by Valence Tautomerization: A One-Pot Approach and Mechanism
- Author
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Srinivas Samala, Ju Young Lee, Jiyoung Kim, and Eun Jeong Yoo
- Subjects
chemistry.chemical_compound ,Diazepine ,Valence (chemistry) ,chemistry ,Mechanism (philosophy) ,Computational chemistry ,Aryl ,Organic Chemistry ,Physical and Theoretical Chemistry ,Ring (chemistry) ,Biochemistry ,Tautomer ,Pyrrole derivatives - Abstract
Herein, we describe the valence tautomerizations of fused 1,4-diazepines, which are reconstructed to give pyrrole derivatives and HCN gas. Several factors that influence the equilibrium between each valence tautomer of an 8π-electron diazepine skeleton are demonstrated. On the basis of these mechanistic studies, a cascade strategy for the construction of diazepines followed by ring contraction is developed to afford aryl- or alkyl-substituted pyrrolo[1,2-a]quinolines that are otherwise challenging to fabricate. In addition, further transformations of the obtained products highlight the advantages of the developed methodology.
- Published
- 2021
24. Synthesis, QSAR modeling, and molecular docking of novel fused 7‐deazaxanthine derivatives as adenosine A 2A receptor antagonists
- Author
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Svitlana V. Shishkina, I. O. Yaremchuk, Vasyl Kovalishyn, Anna M. Zinchenko, Ivan V. Semenyuta, Diana Hodyna, L. V. Muzychka, Oleg B. Smolii, Larysa Metelytsia, and Evgenii V. Verves
- Subjects
Pharmacology ,Quantitative structure–activity relationship ,chemistry.chemical_compound ,Diazepine ,Chemistry ,Adenosine A2A Receptor Antagonists ,Stereochemistry ,Drug Discovery ,Organic Chemistry ,7-deazaxanthine ,Molecular Medicine ,Biochemistry - Abstract
Predictive QSAR models for the search of new adenosine A2A receptor antagonists were developed by using OCHEM platform. The predictive ability of the regression models has coefficient of determination q2 = 0.65-0.71 with cross-validation and independent test set. The inhibition activities of novel fused 7-deazaxanthine compounds were predicted by the developed QSAR models. A preparative method for the synthesis of pyrimido[5',4':4,5]pyrrolo[1,2-a][1,4]diazepine derivatives was developed, and 11 new adenosine A2A receptor antagonists were obtained. Preliminary investigations into the toxicology of fused 7-deazaxanthine compounds toward commonly used model organism to assess toxicity invertebrate cladoceran D. magna were also described.
- Published
- 2021
25. Synthesis of Cu-Porphyrazines by Annulated Diazepine Rings with Electrochemical, Conductance Activities and Computational Studies
- Author
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Asmaa M. Fahim, Asmaa Aboelnaga, Fathy M. Abdelrazek, Hend S. Magar, and Eklass Nasar
- Subjects
Materials science ,Polymers and Plastics ,Infrared spectroscopy ,Carbon-13 NMR ,Electrochemistry ,Dielectric spectroscopy ,chemistry.chemical_compound ,Diazepine ,chemistry ,Solid-state nuclear magnetic resonance ,Polymer chemistry ,Materials Chemistry ,Reactivity (chemistry) ,Cyclic voltammetry - Abstract
In this investigation, we synthesized novel Cu-porphyrazines annulated with diazepines moiteis, the diazepines rings were obtained via 1,4-cycloaddition reactions of chalcone derivatives 1a-d with 2,3-diaminomaleonitrile utilized ultrasonic energy as green source energy to afford the corresponding diazepine derivatives 4a-d. The formed diazepine was characterized by using data from proton and carbon NMR, fourier-transform infrared spectra and Mass spectrum. Furthermore, in one pot system, the diazepine compounds reacted with copper sulfate in the presence of DBU to give Cu-porphyrazines annulated with diazepines moieties. The prepared Cu-porphyrazine rings 5a-d were characterized using solid state NMR, analysed HSQC, FT-IR, and thermal gravimetrical analysis. The Cu-Porphyrazines and diazepine compounds underwent electrochemical behavior such as cyclic voltammetry and impedance spectroscopy to ensure presence of Cu atom in the core of cyclic diazepines rings and approved the oxidation and reduction of these Porphyrazines on the surface and ability of their reactivity. The electrical conductivity of new Cu-porphyrazines were measured. The obtained diazepines and Cu-porphyrazines were investigated through DFT/B3PW91/LANDZ2 basis set and the stability of these compounds was confirmed.
- Published
- 2021
26. Porphyrazines with annulated diazepine rings. 6. Synthesis and properties of the alkyl substituted derivative - MgII complex of tetrakis-2,3-(5,7-di-tert-butyl-6H-1,4-diazepino)porphyrazine
- Author
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Ekaterina N. Tarakanova, Pavel A. Stuzhin, Sergey E. Nefedov, Pavel A. Tarakanov, and Roman S. Kumeev
- Subjects
chemistry.chemical_classification ,Tert butyl ,chemistry.chemical_compound ,Diazepine ,chemistry ,General Chemistry ,Porphyrazine ,Medicinal chemistry ,Tautomer ,Alkyl ,Derivative (chemistry) - Abstract
Novel MgII porphyrazine 3 bearing four appended seven-membered tert-butyl substituted 1,4-diazepine rings was prepared via Linstead macrocyclization of 5,7-di-tert-butyl-6[Formula: see text]-1,4-diazepine-2,3-dicarbonitrile 2, obtained by condensation of diaminomaleonitrile and 2,2,6,6-tetramethylheptanedione-3,5 (1) in anhydrous ethanol in the presence of P2O5. The structure of the dinitrile precursor 2 was established by single crystal X-ray work. 1H NMR study revealed that the 1,4-diazepine ring is present in the 6[Formula: see text] tautomeric form both in the dinitrile precursor 2 and the MgII complex 3. The inversion of the tert-butyl substituted diazepine ring occurs more easily than in the case of aryl and alkenyl substituted species. Although porphyrazine 3exhibit some tendency to aggregation in low-polar solvents the presence of bulky tert-butyl substituents stabilizes the monomeric form and hinders formation of H-bonded dimers characteristic for aryl and styryl substituted analogues.
- Published
- 2021
27. ЗАМІЩЕНІ АМІНОХАЛКОНИ ЯК ВИХІДНІ СПОЛУКИ ДЛЯ ОТРИМАННЯ НОВИХ ПОХІДНИХ 1,4-БЕНЗОДІАЗЕПІНІВ
- Subjects
condensation ,конденсація ,діазепін ,халкон ,acetophenone ,benzaldehyde ,diazepine ,бензальдегід ,chalcone ,ацетофенон - Abstract
The aim of this work is the synthesis of a number of substituted E‑1-(2-amino‑5-R1-phenyl)-3-(4-R2-phenyl)prop‑2-en‑1-ones (2-aminochalcones) as precursors for obtaining new derivatives of 7-R1–5-[2-R2-phenylvinyl]-1,4-benzodiazepin‑2-ones. Starting 5-substituted 2-aminoacetophenones with bromo and nitro group were synthesized from 2-aminoacetophenone by bromination of the latter with N‑bromosuccinimide in acetonitrile and nitration of 2-acetaminoacetophenone with a nitrating mixture followed by removal of acetyl protection. 2-Aminochalcones were synthesized according to standard methods during the interaction of a number of 5-substituted 2-aminoacetophenones with para-substituted benzaldehydes under basic catalysis conditions. The target products turned out to be brightly colored compounds with low melting points, their isolation and purification did not cause any difficulties. According to the data of 1H NMR spectroscopy, all synthesized 2-aminochalcones were individual trans isomers, which was also confirmed by X‑ray structural analysis of one of the obtained 2-aminochalcones. A number of new substituted E‑1-(2-amino‑5R1-phenyl)-3-(4-R2-phenylprop‑2-en‑1-ones) were synthesized – compounds with amino and ketofunctions and are precursors for obtaining of a new series of 5-substituted 1,4-benzodiazepines with various arylvinyl groups. 2-aminoacetophenone, 2-amino‑5-bromoacetophenone, and 2-amino‑5-nitroacetophenone were selected as substrates for this series. The methyl groups of these acetophenones were condensed according to Claisen-Schmidt with parasubstituted benzaldehydes. Condensation was carried out under alkaline conditions in an aqueous solution. Yields of aminochalcones reached 60–85%. The methyl group of 2-aminoacetophenones smoothly reacted with aromatic aldehydes to form the corresponding 2-aminophenylchalcones. The structure of the obtained compounds was confirmed by mass spectrometry and 1H NMR spectroscopy. The structure of one of the chalcones was proved by X‑ray structural analysis. The obtained compounds can be used for the synthesis of 1,4-benzodiazepines with 5-arylvinyl substituents., Синтезовано низку заміщених E‑1-(5-R1–2-амінофеніл)-3-(4-R2-феніл)проп‑2-ен‑1-онiв. Показано, що використана методика синтезу забезпечує високі виходи очікуваних продуктів. Будову синтезованих сполук підтверджено методами 1Н ЯМР спектроскопiї та мас-спектрометрiї, а для сполуки 9 також методом рентгеноструктурного аналізу– РСА.
- Published
- 2022
28. Reaction of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine with benzyltriethylammonium chloride.
- Author
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Kalogirou, Andreas S., Manoli, Maria, and Koutentis, Panayiotis A.
- Subjects
- *
AMMONIUM chloride derivatives , *DIAZINES , *CHEMICAL reactions , *SINGLE crystals , *PYRROLES - Abstract
Graphical abstract Highlights • 3,4,4,5-Tetrachloro-4 H -1,2,6-thiadiazine reacts with cat. BnEt 3 NCl to give a mixture of mono- and polycyclic heterocycles. • Single crystal X-ray studies support the structures of four minor products. • Independent synthesis for 8-bromo-4-chloropyrrolo[2′,1′:2,3]imidazo[4,5- c ][1,2,6]thiadiazine-6,7-dicarbonitrile. Abstract 3,4,4,5-Tetrachloro-4 H -1,2,6-thiadiazine was reacted with BnEt 3 NCl (10 mol%) to give perchloro-9-thia-1,5,8,10-tetraazaspiro[5.5]undeca-1,4,7,10-tetraene (up to 18% yield), 4,5,6-trichloropyrimidine-2-carbonitrile (up to 44% yield) and four minor side products: 2,7-dichlorothiazolo[5,4- d ]pyrimidine-5-carbonitrile, 2-(4-chloro-6 H -thiazolo[5,4- c ][1,2,6]thia-diazin-6-ylidene)malononitrile, 4,8-dichloropyrrolo[2′,1′:2,3]imidazo[4,5- c ][1,2,6]thiadiazine-6,7-dicarbonitrile and 4,7-dichloro-[1,2,6]thiadiazino[3,4- b ]thiazolo[5,4- e ][1,4]diazepin-9(10 H)-one. Single crystal X-ray studies support the structures of the minor products. Tentative rationale for the formation of these minor products and the synthesis of 8-bromo-4-chloropyrrolo[2′,1′:2,3]imidazo[4,5- c ][1,2,6]thiadiazine-6,7-dicarbonitrile are presented. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
29. A novel thiamine-derived pigment, pyrizepine, formed by the Maillard reaction.
- Author
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Igoshi, Asuka, Noda, Kyoko, and Murata, Masatsune
- Subjects
- *
MAILLARD reaction , *VITAMIN B1 - Abstract
To find a Maillard pigment derived from thiamine, a solution containing glucose and thiamine was heated and analyzed with high-performance liquid chromatography equipped with diode-array detection. As a result, a unique peak showing an absorption maximum at 380 nm was detected. This peak was then isolated from a reaction solution containing glucose, lysine and thiamine, and was identified as 1-(2-methyl-6,9-dihydro-5H-pyrimido[4,5-e][1,4]diazepin-7-yl)ethan-1-one using instrumental analyses. This compound, named pyrizepine, was a novel yellow pigment having a fused ring consisting of pyrimidine and diazepine. Pyrizepine was a major low-molecular-weight pigment in the reaction solution. The structure suggests that pyrizepine is formed by condensation reaction between a degradation product of thiamine and a tetrosone derivative formed from glucose by the Maillard reaction. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
30. Synthesis of dipyrrolo-diazepine derivatives via intramolecular alkyne cyclization.
- Author
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Baskın, Dılgeş, Balci, Metin, and Çetinkaya, Yasin
- Subjects
- *
DIAZEPINES , *RING formation (Chemistry) , *DIPYRROMETHANES , *ALKYNES , *REGIOSELECTIVITY (Chemistry) , *PYRROLES - Abstract
A regioselective approach was developed for the synthesis of dipyrrolo-diazepine derivatives. The synthetic route to dipyrrolo-diazepines first involves the synthesis of dipyrromethanes, followed by reaction of propargyl bromide in the presence of NaH to attach one alkyne functionality to the pyrrole nitrogen atom. Intramolecular heterocyclization with NaH in DMF between the alkyne functionality and pyrrole nitrogen atom gave the desired structures in good yields. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
31. Synthesis of a novel fused pyrrolodiazepine-based library with anti-cancer activity.
- Author
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Malik, Neha, Iyamu, Iredia D., Scheidt, Karl A., and Schiltz, Gary E.
- Subjects
- *
CHEMICAL synthesis , *DIAZEPINES , *DRUG development , *MANNICH reaction , *CHEMOSELECTIVITY , *ACYLATION - Abstract
Development of drugs for new and persistent diseases will increasingly rely on the expansion of accessible chemical space to allow exploration of novel molecular targets. Here we report the synthesis of a library of novel fused heterobicyclic small molecules based on the 1,4-diazepine and 2,4-pyrrolidinedione scaffolds. Key chemical transformations included a Mannich-type condensation and chemoselective N -acylation reactions. Screening shows anti-cancer activity of several library compounds which suggests translational potential of this novel chemical scaffold. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
32. Expedient and click synthesis, spectroscopic characterizations and DFT calculations of novel 1,5-bis(N-substituted 1,2,3‒triazole) benzodiazepinedione scaffolds.
- Author
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Paghandeh, Hossein and Saeidian, Hamid
- Subjects
- *
TRIAZOLES synthesis , *AMIDATION , *ALKYNES , *RING formation (Chemistry) , *DENSITY functional theory , *LITHIUM ions , *LITHIATION - Abstract
A practically reliable procedure for synthesis of new 1,5-bis( N -substituted 1,2,3‒triazole) benzodiazepinedione derivatives was reported by sequential amidation, propargylation and a click azide‒alkyne [3 + 2] cycloaddition reaction in a one pot fashion. The desired products were characterized by CHN analysis, 1 H and 13 C NMR and ESI-MS spectroscopy. Short reaction time, good yields (55–91%), mild reaction conditions and easily available and less expensive starting materials are advantages of this protocol. Natural bond orbital charge distribution and HOMO-LUMO analysis of the characterized structure of 4e have been also calculated by density functional theory (DFT) calculations. The Li + and Na + ion affinities of 4e have been also investigated by DFT studies to find the applicability of these products as ligand in coordination chemistry. Sodium ion affinity of 4e was determined as 60 kJ mol −1 is less than its lithium ion affinity, indicating that the lithiation of 4e is more exothermic than the sodiation. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
33. Conformationally rigid derivatives of WAY-267,464: Synthesis and pharmacology at the human oxytocin and vasopressin-1a receptors.
- Author
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Jorgensen, William T., Katte, Timothy A., Reekie, Tristan A., Kassiou, Michael, Gulliver, Damien W., Werry, Eryn L., and Connor, Mark
- Subjects
- *
VASOPRESSIN , *G protein coupled receptors , *OXYTOCIN , *PHARMACOLOGY , *DIAZEPINES , *MICROBIOLOGICAL assay - Abstract
WAY-267,464 ( 1 ) and twelve conformationally rigid analogues ( 3a-f–4a-f ) were synthesised, characterised and evaluated in cellular assays with the aim of systematically exploring interactions with the oxytocin receptor (OTR). Each analogue was evaluated in radioligand binding displacement assays at both human OTR and arginine vasopressin 1a receptors (V 1a R). Physiological characterisation was determined by whole cell IP1 accumulation assays on stably transfected human embryonic kidney (HEK) cells. Incorporation of the rigid, optionally substituted benzene ring abolished OTR activity and diminished V 1a R pharmacology when compared to 1 . A general trend was observed in V 1a R affinity for the propyl analogues ( 3d-3f ) which identified the ortho -substituted analogue as the best in series (Ki = 251 nM) followed by a decrease in affinity through the meta and para -derivatives ( 3e ; Ki = 874 nM and 3f ; Ki = 1756 nM respectively). This study confirms the importance of the central pharmacophoric motifs of WAY-267,464 and illuminates the differences in the binding pocket of the highly conserved OTR and V 1a R. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
34. SYNTHESIS, INVESTIGATION, CHROMATOGRAPHY, THERMAL-BEHAVIOR OF (FIVE, SEVEN)- MEMBERED RING WITH AZO AND ANIL COMPOUNDS.
- Author
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Aljamali, Nagham Mahmood
- Subjects
NITROGEN compounds ,CYCLIC compounds ,RING formation (Chemistry) ,DIAMINES ,CHROMATOGRAPHIC analysis - Abstract
This practical studying includes formation of a new Nitrogen-Cyclic compounds (five and seven membered ring) by azotation reaction and condensation reaction, then cyclization with diamine compounds (phenylene diamine, phenyl hydrazine) by some conditions with catalyst to formation di nitrogen cycle compounds. The structure of all formatted compounds was characterized by using many techniques (FT, IR, ¹H. NMR, Mass Spectra, Chromatography-Measurement, Thermal-Measurements)) then studying of physical and chemical characterization and other chemical studies. [ABSTRACT FROM AUTHOR]
- Published
- 2018
35. Crystal structure, Hirshfeld surface analysis and interaction energy calculation of 4-(furan-2-yl)-2-(6-methyl-2,4-dioxopyran-3-ylidene)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine
- Author
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El Mokhtar Essassi, Joel T. Mague, Bushra Amer, Lhoussaine El Ghayati, Sanae Lahmidi, Nada Kheira Sebbar, Tuncer Hökelek, and Mohamed El Hafi
- Subjects
π-stacking ,crystal structure ,hydrogen bond ,Crystallography ,furan ,Cyclohexane conformation ,Stacking ,tetrahydrobenzodiazepine ,General Chemistry ,Crystal structure ,Dihedral angle ,pyrandione ,Condensed Matter Physics ,Ring (chemistry) ,chemistry.chemical_compound ,Diazepine ,chemistry ,Pyran ,QD901-999 ,Furan ,General Materials Science - Abstract
The title compound {systematic name: (S,E)-3-[4-(furan-2-yl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-2-ylidene]-6-methyl-2H-pyran-2,4(3H)-dione}, C19H16N2O4, is constructed from a benzodiazepine ring system linked to furan and pendant dihydropyran rings, where the benzene and furan rings are oriented at a dihedral angle of 48.7 (2)°. The pyran ring is modestly non-planar [largest deviation of 0.029 (4) Å from the least-squares plane] while the tetrahydrodiazepine ring adopts a boat conformation. The rotational orientation of the pendant dihydropyran ring is partially determined by an intramolecular N—HDiazp...ODhydp (Diazp = diazepine and Dhydp = dihydropyran) hydrogen bond. In the crystal, layers of molecules parallel to the bc plane are formed by N—HDiazp...ODhydp hydrogen bonds and slipped π–π stacking interactions. The layers are connected by additional slipped π–π stacking interactions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (46.8%), H...O/O...H (23.5%) and H...C/C...H (15.8%) interactions, indicating that van der Waals interactions are the dominant forces in the crystal packing. Computational chemistry indicates that in the crystal the N—H...O hydrogen-bond energy is 57.5 kJ mol−1.
- Published
- 2021
36. o-Phenylenediamine as a Source of Fused Azole, Azine, and Diazepine Derivatives
- Author
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N. A. Ismail, A. M. Almostafa, Mohamed G. Assy, and W. Shehta
- Subjects
Diethyl succinate ,chemistry.chemical_compound ,Diazepine ,chemistry ,Nucleophile ,Thiourea ,Organic Chemistry ,Pyridine ,Ammonium thiocyanate ,Chloroacetyl chloride ,Medicinal chemistry ,Diethyl malonate - Abstract
A facile synthetic approach to diazepine and/or benzimidazole derivatives has been developed through the reaction of enamine [N1-(1-phenylethenyl)benzene-1,2-diamine] obtained from o-phenylenediamine and acetophenone. Its reaction with isophthaloyl chloride produced bis(1,5-benzodiazepinyl)benzene derivative via cyclization involving the nucleophilic enamino carbon atom, whereas the cyclocondensation with diethyl succinate occurred at the nucleophilic nitrogen atom to give bis-benzimidazole derivative. Depending on the conditions, the cyclization with carbon disulfide in DMSO afforded tricyclic 4-phenylimidazo[4,5,1-hi]indole-2(1H)-thione, while 4-phenyl-1,3-dihydro-2H-1,5-benzodiazepine-2-thione was formed in the presence of pyridine. Cyclocondensation of o-phenylenediamine with two equivalents of acetophenone in acid medium produced 3-phenyl-1-(1-phenylethenyl)-1,4-dihydroquinoxaline. N-(2-Aminophenyl)thiourea obtained from o-phenylenediamine and ammonium thiocyanate reacted with chloroacetyl chloride, diethyl malonate, carbon disulfide, and sodium nitrite in aqueous HCl to afford benzimidazole, thiadiazolobenzimidazole, and benzotriazole derivatives.
- Published
- 2021
37. Synthesis, density functional theory, and cytotoxic activity of some heterocyclic systems derived from 3-(3-(1,3-diphenyl-1H-pyrazol-4-yl)acryloyl)-2H-chromen-2-one
- Author
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Sameh A. Rizk and Sayed K. Ramadan
- Subjects
Chalcone ,010405 organic chemistry ,General Chemistry ,Pyrazole ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Tautomer ,0104 chemical sciences ,chemistry.chemical_compound ,Diazepine ,chemistry ,Thiourea ,Density functional theory ,Reactivity (chemistry) ,Malononitrile - Abstract
The behavior and reactivity of a coumarin-based chalcone bearing a pyrazole core 3 toward malononitrile, hydrazine, thiourea, hydrazinecarbothioamide, 2-aminoaniline, and 6-aminothiouracil were investigated as an attempt to design and synthesize a novel series of pyrazole-based heterocycles, viz. pyranocoumarin, diazepine, pyrimidochromene, triazepine, benzodiazepine, and pyrimidopyrimidine derivatives. DFT based on quantum chemical computation outlines the structure optimization of the intermediate that reacted to achieve the desired product. The antitumor activity screening against HePG-2 and MCF-7 cancer cell lines disclosed that the most potent compounds against two cell lines were 9 and 17 as compared to doxorubicin which may be attributed to their presence in more tautomeric structures. Also, the minimized energy, dipole moment, ionization potential, transferred electrons, and charge density distribution disclosed that the greater value of 0.126 and 0.8 for pyrazole derivatives 9 and 17, respectively, indicates the maximum transfer of electron and hence greater tendency of scavenging radicals and rapidly reduce oxygen to superoxide.
- Published
- 2021
38. Novel GABAA Agonist Entities: Pharmacological Investigation and Molecular Modeling Study of Thiazolo- and Thiadiazolo-[3,2-a][1,3]diazepine Analogs
- Author
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Hussein I. El-Subbagh
- Subjects
Pharmacology ,Agonist ,Molecular model ,medicine.drug_class ,GABAA receptor ,General Medicine ,chemistry.chemical_compound ,Diazepine ,Drug development ,chemistry ,Drug Discovery ,medicine ,Neuromuscular Blockers ,Biological evaluation - Abstract
Thiazolo- and thiadiazolo-[3,2-a][1,3]diazepines and their patented derivatives, tested with diverse CNS pharmacological activities, constitute an important class of compounds for new drug development. Therefore, research efforts were continued to design, synthesize, and evaluate compounds for their ultra-short, short-acting hypnotic, anticonvulsant, and neuromuscular blocking activities. The present review provides a summary of the work accomplished by these heterocycles and their biological evaluation.
- Published
- 2021
39. Reagent-Based Diversity-Oriented Synthesis of Triazolo[1,5-a][1,4]diazepine Derivatives from Polymer-Supported Homoazidoalanine
- Author
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Petra Králová and Miroslav Soural
- Subjects
chemistry.chemical_compound ,Diazepine ,chemistry ,010405 organic chemistry ,Reagent ,Organic Chemistry ,Alkylation ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,Polymer supported ,Cycloaddition ,0104 chemical sciences - Abstract
Herein, we report the synthesis of skeletally different triazolo[1,5-a][1,4]diazepines starting from immobilized homoazidoalanine. After sulfonylation with 2/4-nitrobenzenesulfonyl chlorides and Mitsunobu alkylation with various alkynols, the corresponding N-substituted nitrobenzenesulfonamides were obtained. Their catalyst-free Huisgen cycloaddition provided immobilized and functionalized triazolo[1,5-a][1,4]diazepines as the key intermediates for further modification. Using the concept of diversity-oriented, reagent-based synthesis, the key intermediates were subsequently converted to heterocycles bearing [5 + 7 + 5], [5 + 7 + 6], and [5 + 7 + 7] scaffolds. Furthermore, the synthesis of spirocyclic triazolodiazepines was developed.
- Published
- 2021
40. (4Z)-4-(2-Oxopropylidene)-1,3-bis(prop-2-en-1-yl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-one
- Author
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Jihad Sebhaoui, Youness El Bakri, Ibtissam Rayni, Khadija El Bourakadi, El Mokhtar Essassi, and Joel T. Mague
- Subjects
crystal structure ,hydrogen bond ,diazepine ,Crystallography ,QD901-999 - Abstract
In the title compound, C18H20N2O2, the diazepin-2-one ring adopts a tub conformation. The conformation of the acetyl group is partially determined by an intramolecular N—H...O hydrogen bond. In the crystal, pairwise C—H...O hydrogen bonds form inversion dimers.
- Published
- 2017
- Full Text
- View/download PDF
41. Shortcut Approach to 1,4-Diazepine from 3-Pyridylnitrene Intermedietes under Mild Condition
- Author
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Siti Mariyah Ulfa, Hideki Okamoto, and Kyosuke Satake
- Subjects
nitropyridine ,diazepine ,ring expansion ,regioselective ,pyridylnitrene ,Chemistry ,QD1-999 - Abstract
The reaction of nitropyridine derivatives and tributylphosphine (Bu3P) with the existence of nucleophilic solvent gives ring expansion product as diazepines in medium yield. Reaction mechanism subjected the formation of phenylnitrene, followed by intramolecular electrophilic insertion reaction to pyridine ring and subsequent ring enlargement. The intermediate in the reaction confirmed by computational calculation using B3LYP/6-31G* level. The intramolecular insertion reaction of pyridylnitrene is considered suppressed by the low HOMO (-9.932 eV) energy level of pyridine ring compared to that of benzene (-9.653 eV), hence 1,4-diazepine is obtained when employed 3-nitro-2,6-lutidine as starting material. The formation of diazepines was confirmed by the analysis of 1H NMR data. Separation of the product mixture using column chromatography on SiO2 was carried out and found to give expected diazepine along with the reduction product.
- Published
- 2014
42. 1,3‐Diazepine: A privileged scaffold in medicinal chemistry
- Author
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Jean Martinez, Nicolas Masurier, and Yohan Malki
- Subjects
Pharmacology ,0303 health sciences ,Scaffold ,Natural product ,Mechanism (biology) ,Drug discovery ,Chemistry, Pharmaceutical ,Purine analogue ,Ligands ,Medicinal chemistry ,Receptors, G-Protein-Coupled ,Coformycin ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Diazepine ,chemistry ,030220 oncology & carcinogenesis ,Drug Discovery ,Humans ,Molecular Medicine ,Moiety ,Signal Transduction ,030304 developmental biology - Abstract
Privileged structures have been widely used as effective templates for drug discovery. While benzo-1,4-diazepine constitutes the first historical example of such a structure, the 1,3 analogue is just as rich in terms of applications in medicinal chemistry. The 1,3-diazepine moiety is present in numerous biological active compounds including natural products, and is used to design compounds displaying a large range of biological activities. It is present in the clinically used anticancer compound pentostatin, in several recent FDA approved β-lactamase inhibitors (e.g., avibactam) and also in coformycin, a natural product known as a ring-expanded purine analogue displaying antiviral and anticancer activities. Several other 1,3-diazepine containing compounds have entered into clinical trials. This heterocyclic structure has been and is still widely used in medicinal chemistry to design enzyme inhibitors, GPCR ligands, and so forth. This review endeavours to highlight the main use of the 1,3-diazepine scaffold and its derivatives, and their applications in medicinal chemistry, drug design, and therapy. We will focus more particularly on the development of enzyme inhibitors incorporating this scaffold, with a strong emphasis on the molecular interactions involved in the inhibition mechanism.
- Published
- 2021
43. New methods for the synthesis of pyrrolo[1,2-x][1,4]diazepines and their (het)arene-annulated analogs (microreview)
- Author
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Elena Y. Zelina
- Subjects
chemistry.chemical_compound ,Annulation ,Diazepine ,chemistry ,Stereochemistry ,Organic Chemistry ,Ring (chemistry) ,Pyrrole - Abstract
The microreview is devoted to the original synthetic methodologies toward pyrrolo[1,2-x][1,4]diazepines and their (het)arene-annulated analogs published over the past 10 years. The approaches are divided into two groups depending on the starting compounds: annulation of the diazepine ring to the pyrrole fragment and simultaneous formation of pyrrole and diazepine rings via dicarbonyl intermediates.
- Published
- 2021
44. Synthesis of (5aS)-2-benzylthio-3-cyano-4,5a,6,7,8,10-hexahydro-5H-pyrrolo[1,2-a]thieno[3,2-e][1,4]diazepine-5,10-diones
- Author
-
A. E. Fedorov, A. M. Shestopalov, A. S. Sigeev, and Lyudmila A. Rodinovskaya
- Subjects
010405 organic chemistry ,Gaussian ,General Chemistry ,Nuclear magnetic resonance spectroscopy ,010402 general chemistry ,Combinatorial synthesis ,01 natural sciences ,0104 chemical sciences ,symbols.namesake ,chemistry.chemical_compound ,Diazepine ,chemistry ,Computational chemistry ,symbols - Abstract
A convenient method was developed for the combinatorial synthesis of substituted (5aS)-2-benzylthio-3-cyano-4,5a,6,7,8,10-hexahydro-5H-pyrrolo[1,2-a]thieno[3,2-e][1,4]-diazepine-5,10-diones. The structure and the most probable conformation of (5aS)-2-benzylthio-3-cyano-4,5a,6,7,8,10-hexahydro-5H-pyrrolo[1,2-a]thieno[3,2-e][1,4]diazepine-5,10-dione in solution was established by NMR spectroscopy and calculations using the Gaussian program.
- Published
- 2021
45. Synthesis of Diazepine and Thiazepine derivatives of 1H-imidazo [4, 5-b] pyridines (Research Article)
- Author
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A. Jeyanthi, Dayakar Gade, and B. Kusuma
- Subjects
chemistry.chemical_compound ,Diazepine ,chemistry ,Thiazepine ,Research article ,Medicinal chemistry - Published
- 2021
46. Synthesis and biological evaluation of the new ring system benzo[f]pyrimido[1,2-d][1,2,3]triazolo[1,5-a][1,4]diazepine and its cycloalkane and cycloalkene condensed analogues
- Author
-
Márió Gajdács, Ferenc Fülöp, Mohamed El Haimer, Márta Palkó, Matti Haukka, and István Zupkó
- Subjects
chemistry.chemical_classification ,General Chemical Engineering ,Cyclohexene ,Alkyne ,General Chemistry ,Medicinal chemistry ,chemistry.chemical_compound ,Cycloalkane ,Diazepine ,chemistry ,Amide ,Azide ,Cycloalkene ,Norbornene - Abstract
Derivatives of the new ring system benzo[f]pyrimido[1,2-d][1,2,3]triazolo[1,5-a][1,4]diazepinone and its cycloalkane and cycloalkene condensed analogues have been conveniently synthesized through a three-step reaction sequence. An atom-economical, one-pot, three-step cascade process engaging five reactive centers (amide, amine, carbonyl, azide, and alkyne) has been performed for the synthesis of alicyclic derivatives of quinazolinotriazolobenzodiazepine using cyclohexane, cyclohexene, and norbornene β-amino amides. The stereochemistry and relative configurations of the synthesized compounds were determined by 1D and 2D NMR spectroscopy and X-ray crystallography. The reaction was also performed using enantiomeric starting materials leading to enantiomeric quinazolinotriazolobenzodiazepine with an ee of 95%. The synthesis of 9H-benzo[f]pyrimido[1,2-d][1,2,3]triazolo[1,5-a][1,4]diazepinone, a new heterocyclic system, was achieved in a good yield using a retro Diels–Alder (RDA) procedure. Some compounds were tested for antiproliferative activities against five human cancer cell lines of gynecological.
- Published
- 2021
47. Oxidative cross-dehydrogenative coupling (CDC) via C(sp2)–H bond functionalization: tert-butyl peroxybenzoate (TBPB)-promoted regioselective direct C-3 acylation/benzoylation of 2H-indazoles with aldehydes/benzyl alcohols/styrenes
- Author
-
Richa Sharma, Sandeep Chaudhary, Lalit Yadav, and Ravi Kant Yadav
- Subjects
Solvent ,Acylation ,chemistry.chemical_compound ,Diazepine ,chemistry ,Chlorobenzene ,Hydrogen bond ,General Chemical Engineering ,Functional group ,Regioselectivity ,Substrate (chemistry) ,General Chemistry ,Medicinal chemistry - Abstract
An efficient, cost-effective, transition-metal-free, oxidative C(sp2)–H/C(sp2)–H cross-dehydrogenative coupling via a C(sp2)–H bond functionalization protocol for the regioselective direct C-3 acylation/benzoylation of substituted 2H-Indazoles 1a–m with substituted aldehydes 2a–q/benzyl alcohols 5a–e/styrenes 6a–e is reported. The operationally simple protocol proceeds in the presence of tert-butyl peroxybenzoate (TBPB) as an oxidant in chlorobenzene (PhCl) as a solvent at 110 °C for 24 h under an inert atmosphere, which furnished a diverse variety of substituted 3-(acyl/benzoyl)-2H-indazoles 3a–q/4a–l in up to 87% yields. The reaction involves a free-radical mechanism and proceeds via the addition of an in situ generated acyl radical (from aldehydes/benzyl alcohols/styrenes) on 2H-indazoles. The functional group tolerance, broad substrate scope, control/competitive experiments and gram-scale synthesis and its application to the synthesis of anti-inflammatory agent 11 and novel indazole-fused diazepine 13 further signify the versatile nature of the developed methodology.
- Published
- 2021
48. Novel Natural Based Diazepines as Effective Corrosion Inhibitors for Carbon Steel in HCl Solution: Experimental, Theoretical and Monte Carlo Simulations.
- Author
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Afia, Laila, Hamed, Othman, Larouj, Mohamed, Lgaz, Hassan, Jodeh, Shehdeh, and Salghi, Rachid
- Abstract
Three new heterocyclic diazepines (CC-diCl, CC-Cl and CC-F) were synthesized for the first time from the natural product curcumin and evaluated as non-toxic corrosion inhibitors for carbon steel (CS) in 1 M HCl. The evaluation was carried out using electrochemical impedance spectroscopy, polarization curves (PDP) measurement, weight loss (WL) and scanning electron microscopy studies. The molecular modeling methods: density functional theory calculations and Monte Carlo simulations were performed to obtain a good insight into the inhibition process. Results obtained from electrochemical techniques and WL tests revealed that, the studied diazepines were effective corrosion inhibitors for CS in the tested medium. Among the evaluated diazepines, CC-diCl showed the highest efficiency. According to the PDP results, the diazepines behaved as mixed-type (cathodic and anodic) inhibitors. A complete thermodynamic study was also performed on the diazepine with the highest efficiency CC-diCl to gain a better understanding of the inhibition process. The adsorption of the diazepines onto CS surface obeyed a Langmuir adsorption isotherm. A good correlation was obtained between the molecular modeling studies and inhibition efficiency ( IE%) of the tested diazepines. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
49. Synthesis and antimicrobial activity of fused isatin and diazepine derivatives derived from 2-acetyl benzofuran.
- Author
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Kenchappa, R., Bodke, Y., Nagaraja, O., and Telkar, S.
- Subjects
- *
ANTI-infective agents , *ISATIN , *DIAZEPINES , *BENZOFURAN , *GLUCOSAMINE synthase - Abstract
Acetyl benzofurans 1a, 1b reacted with isatins 2a- 2f in the presence of pyridine to give corresponding 3-[2-(1-benzofuran-2-yl)-2-oxoethyl]-3-hydroxy-1,3-dihydro-2 H-indol-2-one derivatives 3a- 3l. Dehydration of the latter in acidic media led to the corresponding α,β-unsaturated ketones 4a- 4l. The structures of newly synthesized compounds 3a- 3l and 4a- 4l were established on the basis of analytical and spectral data. The synthesized compounds were screened for their antibacterial and antifungal activities. Compounds 5d, 5f, and 5h displayed excellent antimicrobial activity. The synthesized compounds were studied for docking on the enzyme, Glucosamine-6-phosphate Synthase. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
50. [Bmim][PNiWO]·3HO an organic-inorganic hybrid as catalyst for one-pot pseudo-five-component synthesis of tetrazolyldiazepines.
- Author
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Mousavifaraz, Sajad, Nadealian, Zahra, Mirkhani, Valiollah, and Rahmati, Abbas
- Subjects
- *
NICKEL compounds , *DIAZEPINES , *HETEROGENEOUS catalysts , *CHEMICAL synthesis , *FOURIER transform infrared spectroscopy , *THERMOGRAVIMETRY - Abstract
In this research, two heterogeneous organic-inorganic hybrid catalysts, [bmim][PWO]·3HO and [bmim][PNiWO]·3HO, have been prepared. The catalysts were fully characterized by several techniques such as elemental analyses, Fourier transform infrared spectroscopy, thermo-gravimetric analysis, scanning electron microscope and energy-dispersive X-ray analysis. Next, the hybrid catalysts have been used for the synthesis of functionalized diazepines containing tetrazole ring. Tetrazolyl-1 H-spiro[benzo[b]cyclopenta[e][1,4] diazepines products were obtained in excellent yields and mild experimental conditions using [bmim][PNiWO]·3HO as catalyst. This process was carried out via a one-pot, pseudo-five-component condensation reaction by means of a 1,2-diamine, isocyanide, TMSN3 and two molecules of a linear or cyclic ketone in methanol, at ambient temperature. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
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