- Photochemistry of o-Nitrophenylazide in Matrices. The First Direct Spectroscopic Observation of o-Dinitrosobenzene
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Photolysis of o-nitrophenylazide in an Ar matrix at 12 K produced the mixture of benzofuroxan and a new species, which could be identified as o-dinitrosobenzene on the basis of its IR and UV spectra.
- Murata, Shigeru,Tomioka, Hideo
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- Intramolecular interaction between ortho-azido and azoxy groups as a new way of forming a N-N bond. Synthesis of 2-alkylbenzotriazole 1-oxides
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Heating of 2-(alkyl-NNO-azoxy)-1-azidobenzenes in boiling benzene gave 2-alkyl-benzotriazole 1-oxides (Alk = Me, Et, Pri, and Bu t). This first-order reaction involves an earlier unknown intramolecular interaction between the azido and azoxy groups with simultaneous release of molecular nitrogen. The cyclization rate increases in the following sequence of the alkyl groups: Me i t. Complete assignment of the signals in the 1H, 13C, and 14N NMR spectra of 2-alkylbenzotriazole 1-oxides was performed.
- Lipilin,Karslyan,Churakov,Strelenko,Tartakovsky
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- Mass Spectral Fragmentation of Benzofurazan-1-oxide
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Fragmentations in the mass spectrum of benzofurazan-1-oxide have been studied using linked scan, accelerating voltage scan and mass-analysed ion kinetic energy spectrometric techniques.Major pathways involve NO.+NO. and NO.+CO loss, these double losses occuring in such rapid succession as to appear 'concerted' in some experiments.Minor pathways are loss of CO2, C2N2O2, or C2HN2O2 from the molecular ion.The major fragment ion, m/z 76, in the conventional mass spectrum is not detected in a mass-analysed ion kinetic energy spectrometric experiment with the molecular ion until collision activation is provided.The conventional electron impact spectrum invariably includes ions from benzofurazan which is produced by thermal deoxygenation in the source.
- Dyall, Leonard K.
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- Rates and Products of Reactions of N-Benzoyloxy-2-nitrobenzenamine with Metal Alkoxides
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A major pathway when N-benzoyloxy-2-nitrobenzenamine (1b) reacts with sodium methoxide is attack on carbonyl and production of methyl benzoate. In a competing pathway, proton abstraction is followed by loss of benzoate and formation of 2,1,3-benzoxadiazole N-oxide (4). With the more bulky t-butoxide base, only the latter pathway is followed, though the heterocyclic product undergoes subsequent destruction. Both the detection in the visible spectrum of a red transient intermediate, and a lack of an electron spin resonance spectrum, indicate it to be the anion (2b). The rates of the reactions of potassium t-butoxide with (1b) and N-benzoyloxy-4-nitrobenzenamine (7) are very similar, which rules out the possibility that the ortho-nitro group in (1b) provides neighbouring group assistance for loss of benzoate ion from the anion (2b). Rate measurements show that the loss of benzoate from (2b) is 39 times slower than chloride loss from the analogous anion (2a).
- Dyall, Leonard K.
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- Discovery of novel nitrogenous heterocyclic-containing quinoxaline-1,4-di-N-oxides as potent activator of autophagy in M.tb-infected macrophages
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As a continuation of our research on antimycobacterial agents, a series of novel quinoxaline-1,4-di-N-oxides (QdNOs) containing various nitrogenous heterocyclic moieties at the R6 position were designed and synthesized. Antimycobacterial activities, as well as the cytotoxic effects, of the compounds were assayed. Four compounds (6b, 6f, 6n, and 6o), characterized by 2-carboxylate ethyl or benzyl ester, 6-imidazolyl or 1,2,4-triazolyl, and a 7-fluorine group, exhibited the most potent antimycobacterial activity against M.tb strain H37Rv (MIC ≤ 0.25 μg/mL) with low toxicity in VERO cells (SI = 169.3–412.1). Compound 6o also exhibited excellent antimycobacterial activity in an M.tb-infected macrophage model and was selected for further exploration of the mode of antimycobacterial action of QdNOs. The results showed that compound 6o was capable of disrupting membrane integrity and disturbing energy homeostasis in M.tb. Furthermore, compound 6o noticeably increased cellular ROS levels and, subsequently, induced autophagy in M.tb-infected macrophages, possibly indicating the pathways of QdNOs-mediated inhibition of intracellular M.tb replication. The in vivo pharmacokinetic (PK) profiles indicated that compounds 6o was acceptably safe and possesses favorable PK properties. Altogether, these findings suggest that compound 6o is a promising antimycobacterial candidate for further research.
- Huang, Lingli,Lu, Qirong,Pan, Yuanhu,Qu, Wei,Xie, Shuyu,Yuan, Zonghui,Zhang, Heying,Zhang, Jie
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- Discovery of 1,2,3-triazole based quinoxaline-1,4-di-N-oxide derivatives as potential anti-tubercular agents
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A series of thirty one novel 2-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-3-methylquinoxaline-1,4-dioxide (7a-l), 3-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-6-chloro-2-methylquinoxaline-1,4-dioxide (8a-l) and 2-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-6,7-dichloro-3-methylquinoxaline-1,4-dioxide (9a-g) analogues were synthesized, characterized using various analytical techniques and single crystal was developed for the compounds 8 g and 9f. Synthesized compounds were evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain and two clinical isolates Spec. 210 and Spec. 192. The titled compounds exhibited minimum inhibitory concentration (MIC) ranging from 30.35 to 252.00 μM. Among the tested compounds, 8e, 8 l, 9c and 9d exhibited moderate activity (MIC = 47.6 – 52.0 μM) and 8a exhibited significant anti-tubercular activity (MIC = 30.35 μM). Furthermore, 8e, 8 l, and 9d were found to be less toxic against human embryonic kidney, HEK 293 cell lines. Finally, a docking study was also performed using MTB DNA Gyrase (PDB ID: 5BS8) for the significantly active compound 8a to know the exact binding pattern within the active site of the target enzyme.
- Aggarwal, Himanshu,Ewa, Augustynowicz-Kopec,G?ogowska, Agnieszka,Ghosh, Balaram,Kumar, Banoth Karan,Murugesan, Sankaranarayanan,Nandikolla, Adinarayana,Pulya, Sravani,Sekhar, Kondapalli Venkata Gowri Chandra,Srinivasarao, Singireddi,Suresh, Amaroju
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- Preparation method of mequindox
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The invention provides a preparation method of mequindox. The preparation method comprises the step of performing reaction by taking ortho-nitroaniline, sodium hypochlorite and acetylacetone as raw materials, taking an NaOH/attapulgite compound as a catalyst and taking sodium carboxymethyl cellulose as a solubilizing agent and a homogenizing agent so as to obtain the mequindox. The preparation method of the mequindox, provided by the invention, realizes the purpose of one-step preparation of the mequindox, omits the intermediate treatment step of benzofurazan, and is simple in technology and high in production efficiency. The purity of the prepared mequindox product can reach 99% or more, and the total yield of the prepared mequindox product can reach 84.5% or more, which is equivalent tosingle-step yield of 90% or more, so that the prepared mequindox product has broad application prospects.
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Paragraph 0046-0063
(2019/02/08)
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- Improved synthesis of quinocetone and its two deoxy metabolites
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Oxidation of o-nitroaniline with sodium hypochlorite afforded benzofurazan oxide in 96 % yield, and treatment of benzofurazan oxide with acetylacetone in the presence of triethylamine gave 2-acetyl-3-methyl-quinoxaline--1,4-dioxide in 94 % yield. Finally, condensation of 2-acetyl-3-methyl-quinox-aline-1,4-dioxide with benzaldehyde using 4-(dimethylamino)pyridinium acetate as a catalyst led to quinocetone in 95 % yield. Subsequently, reduction of the synthesized quinocetone with sodium dithionite resulted in two deoxy derivatives, 1-(3-methyl-4-oxido-2-quinoxalinyl)-3-phenyl-2-propen-1-one and 1-(3-methyl-2-quinoxalinyl)-3-phenyl-2-propen-1-one in 88.5 and 92 % yield, respectively. Furthermore, the synthesized quinocetone, and its deoxy derivatives were characterized by1H-NMR,13C-NMR and elemental analysis.
- Li, Yuwen,Qiu, Mei,Bai, Yubin,Qu, Shaoqi,Hao, Zhihui
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p. 265 - 270
(2018/04/12)
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- Cu-Catalyzed π-Core Evolution of Benzoxadiazoles with Diaryliodonium Salts for Regioselective Synthesis of Phenazine Scaffolds
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The Cu-catalyzed regioselective synthesis of phenazine N-oxides was realized from benzoxadiazoles and diaryliodonium salts. The process was initiated by the electrophilic arylation of benzoxadiazoles with diaryliodonium salts and followed by benzocyclization reactions. The further reduction of N-oxides in situ to phenazine scaffolds and deviation to organic fluorescent materials were readily accomplished.
- Sheng, Jinyu,He, Ru,Xue, Jie,Wu, Chao,Qiao, Juan,Chen, Chao
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supporting information
p. 4458 - 4461
(2018/08/09)
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- One-pot methodology for conversion of o-halogen nitrobenzenes to benzofuroxans
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Reaction of o-halonitrobenzenes with sodium azide under reflux of DMF/H2O gives benzofuroxans in one step in moderate to good yields. This is a faster methodology compared to the conventional procedure involving the preparation and subsequent pyrolysis of o-nitrophenyl azides. For comparison, the reaction was also performed under phase-transfer catalysis.
- Leyva, Elisa,Leyva-Ramos, Socorro,Jiménez-Cata?o, Rogelio,de Luna-Méndez, Telma A.,Cárdenas-Chaparro, Agobardo
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supporting information
p. 604 - 608
(2017/03/15)
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- Synthesis, photophysical, electrochemical and single-crystal x-ray diffraction study of (Z)-2-phenyl-3-(5-(4-(thiophen-2-yl)benzo[c][1,2,5]thiadiazol-7-yl)thiophen-2-yl)acrylonitrile
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The optical characteristics, redox properties, thermogravimetric stability and single-crystal X-ray diffraction study of (Z)-2-phenyl-3-(5-(4-(thiophen-2-yl)benzo[c][1,2,5]thiadiazol-7-yl)thiophen-2-yl)acrylonitrile are examined using ultraviolet–visible spectrophotometry, cyclic voltammetry, thermal gravimetric analysis–diffraction scanning calorimetry analysis, single-crystal X-ray diffraction and density functional theory calculations. Evidently, the crystal structure of compound 6 is sustained by a number of weak nonconventional intermolecular forces of attraction such as C-H?…?N, C-H?…?π donor–acceptor interactions.
- Bhanvadia, Viraj J.,Patel, Heta A.,Sharma, Neha N.,Patel, Arun L.
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p. 1052 - 1061
(2016/07/16)
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- Fast preparation of benzofuroxans by microwave-assisted pyrolysis of o-nitrophenyl azides
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Microwave-assisted pyrolysis of o-nitrophenyl azides gives benzofuroxans in good yields in short reaction times.
- Leyva, Elisa,Leyva, Socorro,González-Balderas, Regina M.,De Loera, Denisse,Jiménez-Cata?o, Rogelio
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p. 217 - 218
(2013/09/02)
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- Effect of complexation of 3-aminoquinoxaline-2-carbonitrile 1,4-dioxides with palladium and copper on their anti-T. cruzi activity
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Pd(II) and Cu(II) complexes of 3-aminoquinoxaline-2-carbonitrile 1,4-dioxides were prepared in order to improve the anti-Trypanosoma cruzi activity of these ligands. The in vitro evaluations demonstrated that the metal complexation modified the activity of the ligands in different manners. Except for one compound, complexation with palladium increased the trypanosomicidal activity 20-80-times. Besides, copper also modified favorably the activity, however, the copper compounds resulted less active than the palladium ones, at the studied doses. Springer Science+Business Media, LLC 2011.
- Benitez, Diego,Lavaggi, Maria L.,Gambino, Dinorah,Torre, Maria H.,Cerecetto, Hugo,Gonzalez, Mercedes
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scheme or table
p. 1439 - 1444
(2012/08/27)
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- Benzooxadiazaole-based D-A-D co-oligomers: Synthesis and electropolymerization
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Four D-A-D type co-oligomers have been synthesized by Stille condensation between monostannyl derivatives of furan/thiophene/selenophene/3,4- ethylenedioxythiophene (EDOT) and 4,7-dibromo-benzo[1,2,5]oxadiazole. All these co-oligomers were successfully electrochemically polymerized in dichloromethane and characterized by spectroelectrochemistry. All four polymers possess narrow optical band gap. Spectroelectrochemical studies of polymer films on indium tin oxide revealed that the replacement of donor EDOT with furan/thiophene/ selenophene has affected the low-energy charge-carrier (bipolaron) formation significantly. Kinetic studies based on chronoamperometry show that the polymer P5 (EDOT-capped benzo[1,2,5]oxadiazole system) possess better electrochromic property with high transmittance (66%) in visible region than the other copolymers.
- Pati, Palas Baran,Das, Soumyajit,Zade, Sanjio S.
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p. 3996 - 4003
(2012/11/07)
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- Generation of benzofuroxans by photolysis of crystalline o-nitrophenylazides. A green chemistry reaction
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Several benzofuroxans were obtained by photolysis of crystalline o-nitrophenylazides at ambient temperature. In this particular case, the solid matrix favored the elimination of nitrogen and exclusive formation of heterocyclic benzofuroxan. However, this reaction gives quantitative yields only with crystalline o-nitrophenylazides with a high melting point (above 50 °C).
- Leyva, Elisa,González-Balderas, Regina M.,De Loera, Denisse A.,Jiménez-Cata?o, Rogelio
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experimental part
p. 2447 - 2449
(2012/06/01)
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- D-A-D low band gap molecule containing triphenylamine and benzoxadiazole/benzothiadiazole units: Synthesis and photophysical properties
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Two D-A-D-type low band gap organic dyes based on triphenylamine and benzoxadiazole/benzothiadiazole, 4,7-Bis{5-{4-{2-[4-(N,N-diphenylamino)phenyl]- 1-nitrilethenyl}phenyl}-2-thienyl}-2,1,3-benzoxadiazole (BDNTBX) and 4,7-Bis{5-{4-{2-[4-(N,N-diphenylamino)phenyl]-1-nitrilethenyl}phenyl}-2-thienyl} -2,1,3-benzothiadiazole (BDNTBT) were successfully synthesized. The properties of two compounds were investigated by density functional theory (DFT) calculations, UV-vis absorption spectroscopy, cyclic voltammetry and fluorescence quenching experiment. The calculated ground-state geometries demonstrate intramolecular charge transfer (ICT) occurs in both molecules during the procedure of charge excitation from HOMO to LUMO. From the data in electrochemistry and fluorescence quenching experiments, the molecules reveal lower HOMO energy levels compared with that of P3HT and proper LUMO energy levels to obtain efficient charge separation with PCBM. Two synthesized compounds exhibit broad absorption range covering the whole visible spectral region. These photophysical and electrochemical properties call attention to that our materials are prospective candidates as donor materials for solution-processable organic photovoltaic cells.
- Zeng, Shaohang,Yin, Lunxiang,Jiang, Xueying,Li, Yanqin,Li, Kechang
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scheme or table
p. 229 - 235
(2012/09/07)
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- Effective promotion of beirut reaction by-cyclodextrin in water
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A mild and highly efficient, environmentally friendly procedure has been developed for the conversion from benzofurazan-N-oxides to quinoxaline di-N-oxides in the presence of-cyclodextrin in water at room temperature with excellent yields. The application of cyclodextrin precludes the use of organic solvent, and the catalyst can be recovered and reused in subsequent reactions with the same catalytic activity. Herein, the Beirut reaction is carried out in the medium of water for the first time. The reaction mechanism was proposed based on the inclusion complexation of-cyclodextrin with benzofurazan-N-oxides which was confirmed by 1H NMR, ultraviolet/visible spectrum, and infrared spectroscopy. Copyright
- Sun, Tao,Zhao, Wen-Jing,Hao, Ai-You,Sun, Li-Zhen
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experimental part
p. 3097 - 3105
(2011/09/14)
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- Studies on log Po/w of quinoxaline di-N-oxides: A comparison of RP-HPLC experimental and predictive approaches
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As reported in our previous papers, a series of quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and studied as anti-tuberculosis agents. Here, the capability of the shake-flask method was studied and the retention time (expressed as log K) of 20 compounds were determined by RP-HPLC analysis. We found that the prediction of log P by the RP-HPLC analysis can result in a high accuracy and can replace the shake-flask method avoiding the experimental problems presented by quinoxaline di-N-oxides. The studied compounds were subjected to the ALOGPS module with the aim of comparing experimental log Po/w values and predicted data. Moreover, a preliminary in silico screening of the QSAR relationship was made confirming the influence of reduction peak potential, lipophilicity, H-bond donor capacity and molecular dimension descriptors on anti-tuberculosis activity.
- Moreno, Elsa,Gabano, Elisabetta,Torres, Enrique,Platts, James A.,Ravera, Mauro,Aldana, Ignacio,Monge, Antonio,Perez-Silanes, Silvia
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scheme or table
p. 7893 - 7908
(2011/11/05)
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- Revisiting the thermal decomposition of five ortho-substituted phenyl azides by calorimetric techniques
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The thermal decomposition (TD) of 2-azidophenylmethanol (1), 2-azidobenzenecarbaldehyde (2), 1-(2-azidophenyl)-1-ethanone (3), (2-azidophenyl)(phenyl)methanone (4) and 1-azido-2-nitrobenzene (5) was analysed by DSC, TG and C80 calorimetric techniques under both oxidative and non-oxidative conditions. The TD of these azides in solution is well known to give the corresponding benzoxazoles, generally in good yields, with the exception of azide 1. When both the outcomes from the solid phase and in 'solution phase' TD reactions combined with the results from EI-MS experiments were considered, sufficient information was available to estimate the azides intrinsic molecular reactivity (MIR).
- Cardillo, Paolo,Gigante, Lucia,Lunghi, Angelo,Zanirato, Paolo
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experimental part
p. 191 - 198
(2010/08/04)
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- Simple and practical procedure for the preparation of benzofurazan-N-oxides in the presence of cyclodextrin in neutral condition
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A simple and practical procedure for the aqueous-phase preparation of benzofurazan-N-oxides has been developed in the presence of cyclodextrin at room temperature in neutral condition for the first time. Organic solvent can be precluded for the application of cyclodextrin, which can be recovered and reused in subsequent reactions without loss of activity. The reaction mechanism was studied based on the complexation of cyclodextrin and o-nitroaniline, which was proved by 1H NMR and IR spectroscopy.
- Sun, Tao,Hao, Aiyou,Shen, Jian,Song, Liqiang
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experimental part
p. 4309 - 4314
(2010/01/05)
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- Synthesis of the possible metabolites of quinocetone in animals
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The possible metabolites of quinocetone in animals had been prepared with different selective reagent by three synthetic routes. It was their principal reaction that Na2S2O4 reduced quinoxaline-1,4-dioxide derivatives to quinoxaline derivatives, H 2O2 s oxidized 2-carboxyl-quinoxaline derivatives to 2-carboxyl-quinoxaline-1 -oxide ones and P(OCH3) 3 reduced 2-carboxyl- quinoxaline-1,4-dioxide derivatives to 3-carboxyl-quinoxaline-1-oxide ones. The title compounds ware confirmed with NMR,UV, FAB-MS, et al.
- Li, Jian-Yong,Zhang, Ji-Yu,Zhou, Xu-Zheng,Li, Jin-Shan,Lu, Run-Hua
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- Synthesis of aryl azides via post-cleavage modification of polymer-bound triazenes
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Starting from immobilized arenes on the triazene T1 linker resin, cleavage was achieved by trifluoroacetic acid in the presence of trimethylsilyl azide to obtain aryl azides in good yields and excellent purities. A novel cleavage protocol has been introduced and analytical and preparative applications have been presented.
- Avemaria, Frank,Zimmermann, Viktor,Br?se, Stefan
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p. 1163 - 1166
(2007/10/03)
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- Novel substituted quinoxaline 1,4-dioxides with in vitro antimycobacterial and anticandida activity
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Thirty-six 6(7)-substituted-3-methyl- or 3-halogenomethyl-2-phenylthio-phenylsulphonyl-chloro-quinoxaline 1,4-dioxides belonging to series 3-6 were synthesised and submitted to a preliminary in vitro evaluation for antimycobacterial, anticandida and antibacterial activities. Antitubercular screening showed a generally good activity of 3-methyl-2-phenylthioquinoxaline 1,4-dioxides (3d,e,h-j) against Mycobacterium tuberculosis, and exhibited MIC between 0.39 and 0.78 μg mL-1 (rifampicin MIC=0.25 μg mL-1), whereas in compounds 4d,e, 5a,b,d,e,l and 6b-e,j,l MIC ranged between 1.56 and 6.25 μg mL-1. Results of the antibacterial and anticandida screening showed that 6e and 6l exhibited MIC=0.4 and 1.9 μg mL-1, respectively, against Candida krusei (miconazole MIC=0.9 μg mL-1), and 4i, 5b,d, 6e, MIC=3.9 μg mL-1 against Candida glabrata (miconazole MIC=0.4 μg mL-1), while compounds 3d,l, 5e,l, and 6b,d,e,l showed MIC=15.6 μg mL-1 against Vibrio alginolyticus.
- Carta, Antonio,Paglietti, Giuseppe,Rahbar Nikookar, Mohammad E,Sanna, Paolo,Sechi, Leonardo,Zanetti, Stefania
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p. 355 - 366
(2007/10/03)
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- Synthesis and herbicidal activity of N-oxide derivatives
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As part of an ongoing program on the chemistry and biological activity of N-oxide-containing molecules, a number of novel 1,2,5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline N,N'-dioxide derivatives were synthesized and evaluated for their herbicidal activity. Many of these compounds exhibited moderate to good herbicidal pre-emergence activity against Triticum aestivum. Dose - response studies were done on the more representative compounds (12, 20, and 26). The most active compound, butylcarbamoylbenzo[1,2-c]1,2,5-oxadiazole N-oxide, 26, displayed herbicidal activity at concentrations as low as 24 g/ha.
- Cerecetto, Hugo,Dias, Eduardo,Di Maio, Rossanna,Gonzalez, Mercedes,Pacce, Sandra,Saenz, Patricia,Seoane, Gustavo,Suescun, Leopoldo,Mombru, Alvaro,Fernandez, Grisel,Lema, Marisa,Villalba, Juana
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p. 2995 - 3002
(2007/10/03)
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- 1,2,3-Triazolo [1,5-a][1,4]- and 1,2,3-triazolo[l,5-a]-[1,5]benzodiazepine derivatives: Synthesis and benzodiazepine receptor binding
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This paper reports the synthesis of new 1,2,3-triazolo[1,4]benzodiazepine and 1,2,3-triazolo[1,5]benzodiazepine derivatives and their evaluation toward benzodiazepine receptors. Receptor affinity gradually and remarkably increases by moving the nitrogen atom of the central ring from position 3 through 4 to position 5, to give the most effective compound 6a (K(i) = 150 nM). N-methylation of the diazepine ring (7a) lowers receptorial binding. Introduction of a chlorine atom on the benzene ring doubles the K(i) value (6b) which remains unaltered by the N-methylation (7b).
- Bertelli, Lucia,Biagi, Giuliana,Giorgi, Irene,Livi, Oreste,Manera, Clementina,Scartoni, Valerio,Martini, Claudia,Giannaccini, Gino,Trincavelli, Letizia,Barili, Pier Luigi
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p. 305 - 311
(2007/10/03)
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- 1,2,3-Triazolo[1,5-a]quinoxalines: Synthesis and binding to benzodiazepine and adenosine receptors
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This paper reports the synthesis and binding assays toward benzodiazepine and adenosine A1 and A(2A) receptors of new 1,2,3-triazolo[1,5-a]quinoxalin-4-one derivatives. The prepared compounds show good affinity toward the benzodiazepine receptor (K(i) 53-314 nM); the GABA ratio values suggest an inverse agonist activity for the N(5) unsubstituted compounds 6b-d and an agonist activity for the N(5) methylated compounds 7a-c. Some derivatives of both series show good affinity (K(i) 1 receptorial subtype.
- Bertelli, Lucia,Biagi, Giuliana,Giorgi, Irene,Manera, Clementina,Livi, Oreste,Scartoni, Valerio,Betti, Laura,Giannaccini, Gino,Trincavelli, Letizia,Barili, Pier Luigi
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p. 113 - 122
(2007/10/03)
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- Antimicrobial and anticollagenase activity of phenazine-5, 10-dioxide and derivatives
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Disclosed are chemical agents with unexpected antimicrobial activity against the microbes, especially Porphyromonas gingivalis, known to be important in the cause and progression of gingivitis, periodontitis, and destruction of hard and soft oral tissues leading to tooth loss. The agents have additional unexpected anticollagenase activity useful in the direct mitigation of tissue damage. The agents can be formulated to produce various compositions and dental implements useful in management of peridental diseases, particularly those involving infection with certain gram-negative anaerobes.
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- Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides
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Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy.Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy.The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells.Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and /or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells.Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced.Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxide have reduction potentials significantly more positive than Tirapazamine (Epc -0.90 V).The most potent cytotoxins to cells in culture were the 6,7-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine.The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity.Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro.In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine.This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.
- Monge, Antonio,Palop, Juan A.,Cerain, Adela Lopez de,Senador, Virginia,Martinez-Crespo, Francisko J.,et al.
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p. 1786 - 1792
(2007/10/02)
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- NITROGEN-CONTAINING SPIROCYCLES
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Spirocycles of general structural formula: STR1 are Class III antiarrhythmic agents.
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- Oxidative Cyclizations. VIII. Mechanisms of Oxidation of ortho-Substituted Benzenamines and Improved Cyclizations by Bis(acetato-O)phenyliodine
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Published reports describe the oxidative cyclization of suitable ortho-substituted arenamines to form such products as 2,1-benzisoxazoles, benzofurazan 1-oxides and benzotriazoles, by using bis(acetato-O)phenyliodine at room temperature.However, the reactions are often inconveniently slow.We now report attempts to achieve short reaction times with more powerful iodine(III) oxidants.These often failed to give cyclic products, but the results enable us to argue that the reaction competing with cyclization involves the arenaminyl cation ArN+H.When such cations are predicted to be relatively unstable, the parent arenamine can be rapidly cyclized in high yield by oxidation with bis(acetato-O)phenyliodine in boiling benzene.
- Dyall, Leonard K.,Harvey, Jacqueline J.,Jarman, Tony B.
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p. 371 - 384
(2007/10/02)
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- Benzofuran compounds as class III antiarrhythmic agents
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Compounds of structural formula: STR1 wherein R' is hydrogen or an aromatic ring system, and Q is a substituted nitrogen or a nitrogen containing heterocycle, X and Y are bridging groups and p is 0 or 1, and E is --S-- or --O--, are Class III antiarrhythmic agents.
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- Enthalpies of combustion of 2,4,6-trimethylbenzonitrile, 2,4,6-trimethylbenzonitrile N-oxide, 2,6-dimethylbenzonitrile, 2,4,6-trimethoxybenzonitrile, and 2,4,6-trimethoxybenzonitrile N-oxide: the dissociation ethalpies of the (N-O) bonds
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The standard (pdeg = 0.1 MPa) molar enthalpies of combustion at 298.15 K were measured by static-bomb calorimetry and the standard molar enthalpies of sublimation at 298.15 K were measured by microcalorimetry for the following aromatic nitriles and aromatic nitrile N-oxides: .From the standard molar enthalpies of formation of the gaseous compounds, the molar dissociation enthalpies of the (N-O) bonds were derived: D(N-O)/(kJ*mol-1): trimethylbenzonitrile N-oxide, (222.2 +/- 4.6); trimethoxybenzonitrile N-oxide, (232.8 +/- 3.8).
- Acree, W. E.,Tucker, Sheryl A.,Zvaigzne, Anita I.,Meng-Yan, Yang,Pilcher, G.,Ribeiro da Silva, Maria D. M. C.
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- Class III antiarrhythmic agents
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Compounds of structural formula: STR1 wherein R' is hydrogen or an aromatic ring system, and Q is a substituted nitrogen or a nitrogen containing heterocycle, and E is --S-- or --O--, are Class III antiarrhythmic agents.
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- Reaction of N-Acyloxy-2-nitrobenzenamines.I. Thermolysis in Benzene or Bromobenzene
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N-Acyloxy-2-nitro- and N-acyloxy-2,4-dinitro-benzenamines have been pyrolysed at 140 deg C in benzene or bromobenzene solution.Homolysis ( to form RCO2-radical and ArNH-radical) is ruled out since virtually all the carboxylate is isolated as carboxylic acid.This acid might arise via a concerted elimination process ( the other product being a benzofurazan 1-oxide), or via heterolysis to ArNH01+, RCO21- with subsequent transfer of proton, and cyclization of the singlet 2-nitrophenylnitrene.These simple reactions compete with bimolecular reactions of products with substrate, in which the corresponding amine, azoxy compound and acid anhydride are generated.Attempts to synthesize N-tosyloxy derivatives of nitrobenzenamines gave only thermal decomposition products.N-Trifluoroacetoxy-2,4-dinitrobenzenamine was isolated as a crude product which detonated violently.
- Bryant, Ian R.,Dyall, Leonard K.
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p. 2275 - 2288
(2007/10/02)
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- Oxidative Cyclizations. VII. Cyclization of 2-Substituted Anilines with Alkaline Hypohalite
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The Green-Rowe oxidation of 2-nitroanilines with alkaline hypohlorite, to yield benzofuroxans, is demonstrated by studies of the visible spectra of transient intermediates to proceed through N-chlorination and a singlet nitrene.Two variations on the route to the nitrene are possible.The cyclization step is represented as an internal capture of the nitrene by the ortho substituent, and on this basis the Green-Rowe oxidative cyclization is now extended to anilines whose ortho substituent is benzoyl or phenylazo.It is not however successful for ortho phenyl.Azo compounds were observed as byproducts in some of these reactions, and are shown to arise via N,N-dichloroanilines.
- Dyall, Leonard K.
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p. 2013 - 2026
(2007/10/02)
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- Oxidative Cyclizations. VI Mechanism of Cyclization of N-Chloro-2-nitroanilines to Benzofuroxans under Alkaline Conditions
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An improved synthesis of N-chloro-2-nitroanilines used chlorine in CCl4 solution to halogenate the 2-nitroaniline.Treatment of these CCl4 solutions of the N-chloroamines with methanolic lithium methoxide, or potassium t-butoxide in t-butylalcohol, produced a transient red colour, and quantitative yields of the corresponding benzofuroxan (benzofurazan 1-oxide) were obtained.U.v and e.s.r. spectra indicated that the red species is the conjugate base of the N-chloroamine.On the basis of rate measurements, it is concluded that this red anion ejects chloride ion irreversibly to yield a singlet ortho-nitrophenylnitrene, which then rapidly cyclizes to the benzofuroxan.The ortho-nitro group does not assist in chloride ion ejection.
- Chapman, Kenneth J.,Dyall, Leonard K.,Frith, Lynn K.
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p. 341 - 354
(2007/10/02)
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- Ueber die Synthese von 2,3-Dialkylpyrazinen
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2,3-Dialkylquinoxalines (4), which are available from the reaction of benzofuroxan (1) with ketones and subsequent reduction of the 2,3-dialkylquinoxaline N,N'-dioxides (3), are converted to 2,3-dialkylpyrazines (6) by oxidation-decarboxylation steps.
- Heyns, Kurt,Behse, Ernst,Francke, Wittko
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p. 240 - 245
(2007/10/02)
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