- Reaction of 4-nitro-1,2-phenylenediamine with 1-(4-R-phenyl)-3-(4-nitrophenyl)propenones
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By the reaction of 4-nitro-1,2-phenylenediamine with 1-(p-R-phenyl)-3-(4-nitrophenyl)propenones, Michael adducts with a 1:2 composition have been obtained. A stagewise scheme is proposed for the formation of these compounds. The structure of one of the products has been established by means of x-ray structure analysis. 1996 Plenum Publishing Corporation.
- Kolos,Orlov,Arisa,Shishkin,Struchkov,Vorob'eva
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- Virtual screening identification and chemical optimization of substituted 2-arylbenzimidazoles as new non-zinc-binding MMP-2 inhibitors
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Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases known to exert multiple regulatory roles in tumor progression and invasiveness. This encouraged over the years the approach of MMP, and particularly MMP-2, targeting for anticancer treatment. Early generations of MMP inhibitors, based on aspecific zinc binding groups (ZBGs) assembled on (pseudo)peptide scaffolds, have been discontinued due to the clinical emergence of toxicity and further drawbacks, giving the way to inhibitors with alternative zinc-chelator moieties or not binding the catalytic zinc ion. In the present paper, we continue the search for new non-zinc binding MMP-2 inhibitors: exploiting previously identified compounds, a virtual screening (VS) campaign was carried out and led to the identification of a new class of ligands. The structure-activity relationship (SAR) of the benzimidazole scaffold was explored by synthesis of several analogues whose inhibition activity was tested with enzyme inhibition assays. By performing the molecular simplification approach, we disclosed different sets of single-digit micromolar inhibitors of MMP-2, with up to a ten-fold increase in inhibitory activity and ameliorated selectivity towards off-target MMP-8, compared to selected lead compound. Molecular dynamics calculations conducted on complexes of MMP-2 with docked privileged structures confirmed that analyzed inhibitors avoid targeting the zinc ion and dip inside the S1′ pocket. Present results provide a further enrichment of our insights for the design of novel MMP-2 selective inhibitors.
- Agamennone, Mariangela,Caradonna, Alessia,Di Pizio, Antonella,Laghezza, Antonio,Loiodice, Fulvio,Luisi, Grazia,Piemontese, Luca,Tortorella, Paolo
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- Synthesis of new TCH/Ni-based nanocomposite supported on SBA-15 and its catalytic application for preparation of benzimidazole and perimidine derivatives
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A stable nickel-decorated SBA-15 nanocomposite (Ni/TCH@SBA-15) was synthesized through surface modification of silica nanoparticles with 3-chloropropyltriethoxysilane (CPTES) and thiocarbohydrazide (TCH) followed by metal–ligand coordination with Ni (II). The structure of this organometallic nanocomposite was characterized by Fourier transform-infrared, field emission-scanning electron microscopy, EDAX, transmission electron microscopy, atomic absorption spectroscopy and N2 adsorption–desorption (Brunauer–Emmett–Teller) techniques. The catalytic performance of Ni/TCH@SBA-15 (NNTS-15) was determined for the synthesis of 2-aryl-substituted benzimidazoles and 2,3-dihydroperimidines. The excellent yields within shorter reaction times, simplicity of catalytic methods, non-toxicity and clean reactions, mild reaction conditions and easy work-up procedure are the important merits of these synthetic protocols. Moreover, the Ni (II) bonded to the SBA-15 surface was stable under the catalytic reaction conditions resulting in its efficient recycling and reuse.
- Kalhor, Mehdi,Rezaee-Baroonaghi, Fahimeh,Dadras, Akbar,Zarnegar, Zohre
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- Synthesis of benzimidazole and quinoxaline derivatives using reusable sulfonated rice husk ash (RHA-SO3H) as a green and efficient solid acid catalyst
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In this work, a simple, rapid and efficient method for the preparation of benzimidazoles and quinoxalines from the condensation of o-phenylene diamines with aldehydes and/or 1,2-dicarbonyl compounds in the presence of sulfonated rice husk ash (RHA-SO3H) as an efficient green catalyst is reported. RHA-SO3H can be easily prepared using a readily available organic compound by simple modification of rice husk ash. All reactions are performed under mild reaction conditions with high to excellent yields. The method is applicable to aromatic, unsaturated and hetero aromatic aldehydes. The advantages of this method are short reaction times, milder conditions, easy work-up, solvent-free conditions and catalyst reusability.
- Shamsi-Sani, Mahnaz,Shirini, Farhad,Abedini, Masoumeh,Seddighi, Mohadeseh
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p. 1091 - 1099
(2016/04/26)
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- Preparation, characterization, and application of 1,1′-disulfo-[2,2′-bipyridine]-1,1′-diium chloride ionic liquid as an efficient catalyst for the synthesis of benzimidazole derivatives
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In this study, 2,2′-bipyridine was treated with chlorosulfonic acid and 1,1′-disulfo-[2,2′-bipyridine]-1,1′-diium chloride, [BiPy](SO3H)2Cl2, as a new ionic liquid catalyst was obtained and characterized with a variety of techniques including IR, 1H, and 13C NMR, Hammett acidity function as well as mass spectra method. After preparation and characterization, this ionic liquid was used as an efficient catalyst for the green and mild synthesis of benzimidazole derivatives. In addition, this reagent is efficiently able to catalyze the preparation of benzimidazole derivatives from the protected derivatives of aldehydes including oximes and semicarbazones. All reactions are performed under mild conditions in excellent yields.
- Shirini, Farhad,Abedini, Masoumeh,Seddighi, Mohadeseh,Arbosara, Fatemeh Shaabani
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p. 7683 - 7693
(2015/02/19)
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- One-pot synthesis of benzimidazoles in water in the presence of SiO 2-OPO3H
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Silica-bound phosphoric acid (SiO2-OPO3H), as an eco-friendly, reusable, and heterogeneous catalyst, was applied for synthesis of 2-substituted benzimidazoles in water at 70°C. Very short reaction times, clean work-up, and high yields are among the advantages of this protocol.
- Mirjalili,Bamoniri,Rahimi Kazerouni
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- Benzimidazole derivatives: Synthesis, leishmanicidal effectiveness, and molecular docking studies
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Leishmanolysin GP63 is a zinc metalloprotease, expressed at the surface of Leishmania promastigotes. Studies on this protein are hindered as only a limited number of effective non-toxic inhibitors of this drug target are known. Present study describes the identification of a variety of 2-aryl- and 5-nitro-2-arylbenzimidazoles as new GP63 inhibitors. All the compounds were tested for in vitro activity against the promastigote form of Leishmania major and showed very good activity. 2-(Thiophen-2-yl)-1H-benzimidazole (19) and 2-(1H-indol-3-yl)-5-nitro-1H-benzimidazole (34) with IC50 value of 0.62 μg/mL were identified as lead of this library. Molecular docking studies were performed on binding site of GP63 to study the binding mode of compounds. The results of both in vitro and in silico studies clearly indicated that benzimidazoles may serve as new drug candidates in the combat against leishmaniasis.
- Shaukat, Awais,Mirza, Hira M.,Ansari, Amna H.,Yasinzai, Masoom,Zaidi, Sohail Z.,Dilshad, Sana,Ansari, Farzana L.
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p. 3606 - 3620
(2013/07/26)
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- DBSA mediated chemoselective synthesis of 2-substituted benzimidazoles in aqueous media
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An efficient synthetic method has been developed for the facile synthesis of 2-substituted benzimidazoles in organized aqueous media in the presence of a surfactant (viz. DBSA) as catalyst and I2 as co-catalyst. The method described has the advantages of operational simplicity, excellent yields, high chemoselectivity, and clean and green reaction profile.
- Kumar, Vikash,Khandare, Dipratn G.,Chatterjee, Amrita,Banerjee, Mainak
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p. 5505 - 5509
(2013/09/23)
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- New strategy for the synthesis of 2-phenylbenzimidazole derivatives with sodium perborate (SPB) as oxidant
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A novel strategy for the synthesis of 2-phenylbenzimidazoles with sodium perborate (SPB) as oxidant under mild reaction condition is developed. Excellent chemoselectivity and broad substrate tolerance are the main advantages of this route.
- Yuan, Jun,Zhao, Zhenjiang,Zhu, Weiping,Li, Honglin,Qian, Xuhong,Xu, Yufang
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p. 7026 - 7030
(2013/07/26)
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- Selectivity control during the solid supported protic acids catalysed synthesis of 1,2-disubstituted benzimidazoles and mechanistic insight to rationalize selectivity
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Selectivity control during the formation of 1,2-disubstituted benzimidazoles has been achieved for the reaction of o-phenylenediamine with aldehydes in the presence of solid supported protic acids as catalysts and choosing an appropriate reaction medium. Perchloric acid adsorbed on silica-gel (HClO4-SiO2) was found to be the most effective catalyst system for the synthesis of 1,2-disubstituted benzimidazoles in EtOH at rt. Apart from the catalyst and solvent, the electronic and steric factors of the aldehyde and the electronic factor of the o-phenylenediamine are also significant contributory factors in dictating the selectivity. An understanding of the mechanistic course of the formation of the 1,2-disubstituted benzimidazoles has been outlined that would rationalise the origin of selectivity control under the set experimental parameters. The Royal Society of Chemistry.
- Kumar, Dinesh,Kommi, Damodara N.,Chebolu, Rajesh,Garg, Sanjeev K.,Kumar, Raj,Chakraborti, Asit K.
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- Fast and efficient method for the synthesis of 2-arylbenzimidazoles using MCM-41-SO3H
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Nanosized MCM-41-SO3H material based on ordered mesoporous silica gel with covalently attached sulfonic acid groups was synthesized and used as acid catalyst for green synthesis of 2-substituted benzimidazole derivatives. Echofriendly protocol, short reaction times, easy and quick isolation of the products, and excellent yields are the main advantages of this procedure. Copyright by Walter de Gruyter.
- Mahdavinia, Gholam Hossein,Rostamizadeh, Shahnaz,Amani, Ali Mohammad,Sepehrian, Hamid
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experimental part
p. 33 - 37
(2012/07/28)
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- One-pot synthesis of benzimidazoles and benzothiazoles in the presence of Fe(HSO4)3 as a new and efficient oxidant
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A series of substituted benzimidazoles and benzothiazoles were prepared through the one-pot reaction of ophenylenediamine and o-aminothiophenol with various aldehydes in the presence of ferric hydrogensulfate both in EtOH and water as solvent. The reactions proceed smoothly in excellent yield, high chemoselectivity and with an easy work-up.
- Eshghi, Hossein,Rahimizadeh, Mohammad,Shiri, Ali,Sedaghat, Parisa
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experimental part
p. 515 - 518
(2012/04/23)
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- 6-Nitrobenzimidazole derivatives: Potential phosphodiesterase inhibitors: Synthesis and structure-activity relationship
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6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC50 values between 1.5 ± 0.043 and 294.0 ± 16.7 μM. Compounds 30 (IC50 = 1.5 ± 0.043 μM), 1 (IC50 = 2.4 ± 0.049 μM), 11 (IC50 = 5.7 ± 0.113 μM), 13 (IC50 = 6.4 ± 0.148 μM), 14 (IC50 = 10.5 ± 0.51 μM), 9 (IC50 = 11.49 ± 0.08 μM), 3 (IC50 = 63.1 ± 1.48 μM), 10 (IC50 = 120.0 ± 4.47 μM), and 6 (IC50 = 153.2 ± 5.6 μM) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC50 = 274 ± 0.007 μM), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. A structure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters.
- Khan,Shah, Zarbad,Ahmad,Ambreen,Khan,Taha,Rahim,Noreen,Perveen,Choudhary,Voelter
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experimental part
p. 1521 - 1526
(2012/04/23)
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- Mild and efficient synthesis of benzimidazole using lead peroxide under solvent-free conditions
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Benzimidazole derivatives have been synthesized using a catalytic amount of lead peroxide (PbO2) at room temperature with excellent yields. The remarkable selectivities under mild, neutral and solvent-free conditions and use of a commercially available, inexpensive catalyst are attractive features of this method. Copyright
- Patil, Vishvanath D.,Patil, Jaymala,Rege, Priyanka,Dere, Ganesh
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experimental part
p. 58 - 62
(2011/03/19)
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- Synthesis and preliminary evaluation of selected 2-aryl-5(6)-nitro- 1H-benzimidazole derivatives as potential anticancer agents
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In this study we report the synthesis and preliminary evaluation of a series of six 2-aryl-5(6)-nitro-1H-benzimidazole derivatives (1-6) as potential anticancer agents. Cytotoxicity was evaluated against seven human neoplastic cell lines using the MTT assay. Compound 6 [2-(4-chloro-3-nitrophenyl)-5(6)- nitro-1H-benzimidazole] was the most active of the series, showing an IC 50 of 28 nM against the A549 cell line. This compound displayed a selective in vitro cytotoxic activity index (>700) in non neoplastic HACAT cells (IC50 = 22.2 μM). Compounds 3 and 6 induce arrest in the S phase of the cell cycle, and compounds 1-6 induce apoptosis in the K562 cell line. Compound 6 induces poly (ADP-ribose) polymerase (PARP) inhibition activity as a potential mechanism of action. These results suggest that compound 6 could be a potent anticancer agent. Compound 3 displayed the best inhibitory activity against PARP with an IC50 value of 0.05 μM, compared to the activity shown by the positive control 3-aminobenzamide (IC50 = 28.5 μM).
- Romero-Castro, Aurelio,Leon-Rivera, Ismael,Avila-Rojas, Laura Citlalli,Navarrete-Vazquez, Gabriel,Nieto-Rodriguez, Alejandro
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experimental part
p. 181 - 189
(2012/02/16)
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- Solvent-free chemoselective synthesis of some novel substituted 2-arylbenzimidazoles using amino acid-based prolinium nitrate ionic liquid as catalyst
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A simple and eco-friendly protocol for the synthesis of substituted 2-arylbenzimidazoles is described. In this process, 2-arylbenzimidazoles were prepared in the presence of a newly introduced ionic liquid prolinium nitrate [Pro]NO3 as catalyst, under solvent-free condition. This process was performed under mild condition without using any oxidant with good to excellent yields and remarkable chemoselectivity in the absence of any byproduct. The ionic liquid can be recovered easily and reused.
- Rostamizadeh, Shahnaz,Aryan, Reza,Ghaieni, Hamid Reza,Amani, Ali Mohammad
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scheme or table
p. 74 - 78
(2009/05/07)
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- Very fast and efficient synthesis of some novel substituted 2-arylbenzimidazoles in water using ZrOCl2?nH2O on montmorillonite K10 as catalyst
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A simple and eco-friendly protocol for the synthesis of some novel substituted 2-arylbenzimidazoles was developed. In this process, these compounds were prepared in water as the solvent using ZrOCl2?nH 2O supported on montmorillonite K10 as an efficient water tolerating Lewis acid. The reaction was performed under mild conditions with good to excellent yields and remarkable chemoselectivity in the absence of any byproduct.
- Rostamizadeh, Shahnaz,Amani, Ali Mohammad,Aryan, Reza,Ghaieni, Hamid Reza,Norouzi, Leila
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experimental part
p. 547 - 552
(2010/06/16)
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- A simple and efficient one-pot synthesis of 2-substituted benzimidazoles
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A simple and efficient procedure for the synthesis of substituted benzimidazoles through a one-pot condensation of o-phenylenediamines with aryl aldehydes in the presence of H2O2/HCl system in acetonitrile at room temperature is described. Short reaction time, large-scale synthesis, easy and quick isolation of the products, and excellent yields are the main advantages of this procedure. Georg Thieme Verlag Stuttgart.
- Bahrami, Kiumars,Khodaei, Mohammad Mehdi,Kavianinia, Iman
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p. 547 - 550
(2008/01/03)
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- Studies on analgesic and anti-inflammatory activities of 1- dialkylaminomethyl-2-(p-substituted phenyl)-5-substituted benzimidazole derivatives
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In this study the analgesic and anti-inflammatory activity of 1,2,5- trisubstituted benzimidazole derivatives have been examined. Analgesic activities of these compounds were investigated by using the modified Koster test. Among the compounds synthesized especially compound 1g (1- diethylaminomethyl)-2-(p-chlorophenyl)-5-nitro benzimidazole hydrochloride) has shown higher activity than acetylsalicylic acid (ASA) and indometacin. Compound 1e (1-(diethylaminomethyl)-2-(p-methoxyphenyl)-5-nitro benzimidazole hydrochloride, 1f (1-(diethylaminomethyl)-2-(p-tolyl)-5-nitro henzimidazole hydrochloride and 1i (1-(pipenridinomethyl)-2-(p-methoxyphenyl)-5-nitro benzimidazole hydrochloride) proved as potent as the standard ASA. Therefore the compounds 1e, 1f, 1g and 1i were screened for their anti-inflammatory activities using the carrageenan-induced hind paw edema test. Except 1g all compounds were almost inactive against this model of inflammation compared to indometacin.
- Ersan, Seyhan,Nacak, Sultan,Noyanalpan, Ningur,Yesilada, Erdem
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p. 834 - 836
(2007/10/03)
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- Synthesis and antimicrobial activity of 1-dialkylaminomethyl-2-(p-substituted phenyl)-5-substituted benzimidazole derivatives
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1-(Dialkylaminomethyl)-2-(p-substituted phenyl)-5-substituted benzimidazole derivatives 1 have been synthesized by reacting 2-phenylbenzimidazole derivatives with formaldehyde and a secondary amine. The derivatives of 2-phenylbenzimidazole were obtained by reacting the bisulfide addition product of substituted benzaldehydes with 4-substituted-o-phenylenediamines. Their structures were confirmed by microanalysis, IB and NMB spectral analysis. Antimicrobial activity of the compounds was investigated by the microdilution susceptibility test in Mueller-Hinton Broth and Sabouraud Dextrose Broth was used for the determination of antibacterial and antifungal activities. Test organisms: Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as Gram-positive bacteria, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 as Gram-negative bacteria, and Candida albicans, C. parapsilosis, C. stellatoidea as yeast-like fungi. Compounds 1a, 1b, 1c, 1e and 1i showed slight to moderate activity against all microorganisms. Compound 1g showed the highest activity. It was found more potent than streptomycin against Enterococcus faecalis and Pseudomonas aeruginosa.
- Ersan, Seyhan,Nacak, Sultan,Acar, Nilguen,Noyanalpan, Ningur
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p. 410 - 412
(2007/10/03)
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- Synthesis of Aromatic Derivatives of 1,5-Benzodiazepine in the Reaction of 4-Nitro-o-phenylenediamine with Chalcone Dibromides
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The reaction of 4-nitro-o-phenylenediamine with 4-nitro-4'-R-chalcone dibromides affords the corresponding β-(2-amino-4-nitroanilino)chalcones; x-ray diffraction data indicate that these are the Z-isomers.Experiments have been performed to determine the conditions required for cyclization of these compounds into 2,4-diaryl-7(8)-nitro-1,5-benzodiazepines.In the solid phase or in ethanol solutions, these compounds exist primarily in the 3H tautomeric form; but in DMSO solutions, the 1H form predominates.
- Kolos, N. N.,Orlov, V. D.,Yuzefovskaya, E. Ya.,Yaremenko, F. G.,Vorob'eva, N. P.,et al.
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p. 827 - 834
(2007/10/03)
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- AN EXPEDIENT ROUTE TO 1H-BENZIMIDAZOLES AND 1H-IMIDAZOPYRIDINES
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1H-Benzimidazoles, 1H-imidazopyridines, and 1H-imidazopyridines can be synthesized readily by reaction of unisolated N-(1-chloroalkyl)pyridinium chlorides with 1,2-benzenediamines, 2,3-pyridinediamine, and 3,4-pyridinediamine, respectively.
- Eynde, Jean-Jacques Vanden,Mayence, Annie,Maquestiau, Andre,Anders, Ernst
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p. 357 - 364
(2007/10/02)
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- A convenient approach to the synthesis of quinoxalines from isoxazolones and 1,2-diaminobenzenes
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2-Aryl-6,7-(un)substituted-quinoxalines (3a-t) and 2-arylbenzimidazoles (4a-t) have been obtained by condensation of 3-aryl-5(4H)-isoxazolones (1a-e) and 4-(un)substituted-1,2-diaminobenzenes (2a-d) under neutral conditions.The mechanism of their formation is illustrated.
- Rao, M Hanmantha,Reddy, A Pandu Ranga,Veeranagaiah, V
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