- Characterization and photocatalytic behavior of 2,9-di(aryl)-1,10-phenanthroline copper(i) complexes
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The synthesis, characterization, photophysical properties, theoretical calculations, and catalytic applications of 2,9-di(aryl)-1,10-phenanthroline copper(i) complexes are described. Specifically, this study made use of di(aryl)-1,10-phenanthroline ligands including 2,9-di(4-methoxyphenyl)-1,10-phenanthroline (1), 2,9-di(4-hydroxyphenyl)-1,10-phenanthroline (2), 2,9-di(4-methoxy-3-methylphenyl)-1,10-phenanthroline (3), and 2,9-di(4-hydroxy-3-methylphenyl)-1,10-phenanthroline (4). The 2:1 ligand-to-metal complexes, as PF6- salts, i.e., ([Cu·(1)2]PF6, [Cu·(2)2]PF6, [Cu·(3)2]PF6, and [Cu·(4)2]PF6) have been isolated and characterized. The structures of ligands 1 and 2 and complexes [Cu·(1)2]PF6 and [Cu·(3)2]PF6 have been determined by single-crystal X-ray analysis. The photoredox catalytic activity of these copper(i) complexes was investigated in an atom-transfer radical-addition (ATRA) reaction and the results showed fairly efficient activity, with a strong wavelength dependence. In order to better understand the observed catalytic activity, photophysical emission and absorption studies, and DFT calculations were also performed. It was determined that when the excitation wavelength was appropriate for exciting into the LUMO+1 or LUMO+2, catalysis would occur. On the contrary, excitations into the LUMO resulted in no observable catalysis. In light of these results, a mechanism for the ATRA photoredox catalytic cycle has been proposed.
- Cetin, M. Mustafa,Hodson, Roman T.,Hart, C. Robin,Cordes, David B.,Findlater, Michael,Casadonte, Dominick J.,Cozzolino, Anthony F.,Mayer, Michael F.
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Read Online
- Eco-Friendly Methodology for the Formation of Aromatic Carbon–Heteroatom Bonds by Using Green Ionic Liquids
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A new sustainable method is reported for the formation of aromatic carbon–heteroatom bonds under solvent-free and mild conditions (no co-oxidant, no strong acid and no toxic reagents) by using a new type of green ionic liquid. The bromination of methoxy arenes was chosen as a model reaction. The reaction methodology is based on only using natural sodium bromine, which is transformed into an electrophilic brominating reagent within an ionic liquid, easily prepared from the melted salt FeCl3 hexahydrate. Bromination reactions with this in-situ-generated reagent gave good yields and excellent regioselectivity under simple and environmentally friendly conditions. To understand the unusual bromine polarity reversal of sodium bromine without any strong oxidant, the molecular structure of the reaction medium was characterised by Raman and direct infusion electrospray ionisation mass spectroscopy (ESI-MS). An extensive computational investigation using density functional theory methods was performed to describe a mechanism that suggests indirect oxidation of Br? through new iron adducts. The versatility of the methodology was successively applied to nitration and thiocyanation of methoxy arenes using KNO3 and KSCN in melted hexahydrated FeCl3.
- Richards, Kenza,Petit, Eddy,Legrand, Yves-Marie,Grison, Claude
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supporting information
p. 809 - 814
(2020/11/30)
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- Cooperativity within the catalyst: alkoxyamide as a catalyst for bromocyclization and bromination of (hetero)aromatics
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Alkoxyamide has been reported as a catalyst for the activation ofN-bromosuccinimide to perform bromocyclization and bromination of a wide range of substrates in a lipophilic solvent, where adequate suppression of the background reactions was observed. The key feature of the active site is the alkoxy group attached to the sulfonamide moiety, which facilitates the acceptance as well as the delivery of bromonium species from the bromine source to the substrates.
- Mondal, Haripriyo,Sk, Md Raja,Maji, Modhu Sudan
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supporting information
p. 11501 - 11504
(2020/10/12)
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- Decarboxylative Suzuki-Miyaura coupling of (hetero)aromatic carboxylic acids using iodine as the terminal oxidant
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A novel methodology for the decarboxylative Suzuki-Miyaura-type coupling has been established. This process uses iodine or a bromine source as both the decarboxylation mediator and the terminal oxidant, thus avoiding the need for stoichiometric amounts of transition metal salts previously required. Our new protocol allows for the construction of valuable biaryl architectures through the coupling of (hetero)aromatic carboxylic acids with arylboronic acids. The scope of this decarboxylative Suzuki reaction has been greatly diversified, allowing for previously inaccessible non-ortho-substituted aromatic acids to undergo this transformation. The procedure also benefits from low catalyst loadings and the absence of stoichiometric transition metal additives.
- Quibell, Jacob M.,Duan, Guojian,Perry, Gregory J.P.,Larrosa, Igor
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supporting information
p. 6445 - 6448
(2019/06/07)
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- Environmentally benign indole-catalyzed position-selective halogenation of thioarenes and other aromatics
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Halogenated aromatic compounds are the cores of many pharmaceutical, agricultural and chemical products but they are commonly prepared using electrophilic halogenation reactions in non-green chlorinated solvents under harsh conditions. A separate problem happens in the aromatic halogenation of thioarenes because they readily undergo oxidative side-reactions. Herein we report an environmentally benign electrophilic bromination of aromatics using an indole-catalytic protocol, which is suitable for a wide range of substrates including thioarenes.
- Shi, Yao,Ke, Zhihai,Yeung, Ying-Yeung
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supporting information
p. 4448 - 4452
(2018/10/17)
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- Transition-metal-free decarboxylative bromination of aromatic carboxylic acids
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Methods for the conversion of aliphatic acids to alkyl halides have progressed significantly over the past century, however, the analogous decarboxylative bromination of aromatic acids has remained a longstanding challenge. The development of efficient methods for the synthesis of aryl bromides is of great importance as they are versatile reagents in synthesis and are present in many functional molecules. Herein we report a transition metal-free decarboxylative bromination of aromatic acids. The reaction is applicable to many electron-rich aromatic and heteroaromatic acids which have previously proved poor substrates for Hunsdiecker-type reactions. In addition, our preliminary mechanistic study suggests that radical intermediates are not involved in this reaction, which is in contrast to classical Hunsdiecker-type reactivity. Overall, the process demonstrates a useful method for producing valuable reagents from inexpensive and abundant starting materials.
- Quibell, Jacob M.,Perry, Gregory J. P.,Cannas, Diego M.,Larrosa, Igor
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p. 3860 - 3865
(2018/04/26)
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- Zwitterionic-Salt-Catalyzed Site-Selective Monobromination of Arenes
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A zwitterionic-salt-catalyzed electrophilic monobromination of arenes with high regioselectivity has been developed. Under mild reaction conditions, a wide range of monobrominated aromatic compounds can be obtained in excellent yields. The reaction can be operated using an extremely low catalyst loading (0.05 mol %) with the inexpensive brominating agent N-bromosuccinimide. The versatility of this catalytic protocol has been demonstrated by the scale-up reaction with a 0.01 mol % catalyst loading to provide the selectively halogenated compound in quantitative yield.
- Xiong, Xiaodong,Tan, Fei,Yeung, Ying-Yeung
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supporting information
p. 4243 - 4246
(2017/08/23)
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- Intermolecular Aryl C?H Amination through Sequential Iron and Copper Catalysis
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A mild, efficient and regioselective method for para-amination of activated arenes has been developed through a combination of iron and copper catalysis. A diverse range of products were obtained from an operationally simple one-pot, two-step procedure involving bromination of the aryl substrate with the powerful Lewis acid iron(III) triflimide, followed by a copper(I)-catalysed N-arylation reaction. This two-step dehydrogenative process for the regioselective coupling of aromatic C?H bonds with non-activated amines was applicable to anisole-, phenol-, aniline- and acetanilide-type aryl compounds. Importantly, the arene substrates were used as the limiting reagent and required no protecting-group manipulations during the transformation.
- Mostafa, Mohamed A. B.,Calder, Ewen D. D.,Racys, Daugirdas T.,Sutherland, Andrew
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supporting information
p. 1044 - 1047
(2017/02/05)
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- Selective Halogenation Using an Aniline Catalyst
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Electrophilic halogenation is used to produce a wide variety of halogenated compounds. Previously reported methods have been developed mainly using a reagent-based approach. Unfortunately, a suitable "catalytic" process for halogen transfer reactions has yet to be achieved. In this study, arylamines have been found to generate an N-halo arylamine intermediate, which acts as a highly reactive but selective catalytic electrophilic halogen source. A wide variety of heteroaromatic and aromatic compounds are halogenated using commercially available N-halosuccinimides, for example, NCS, NBS, and NIS, with good to excellent yields and with very high selectivity. In the case of unactivated double bonds, allylic chlorides are obtained under chlorination conditions, whereas bromocyclization occurs for polyolefin. The reactivity of the catalyst can be tuned by varying the electronic properties of the arene moiety of catalyst.
- Samanta, Ramesh C.,Yamamoto, Hisashi
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supporting information
p. 11976 - 11979
(2015/08/18)
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- A Metal-Free and Ionic Liquid-Catalyzed Aerobic Oxidative Bromination in Water
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A metal-free aerobic oxidative bromination of aromatic compounds in water has been developed. Hydrobromic acid is used as a bromine source and 2-methylpyridinium nitrate ionic liquid is used as a recyclable catalyst. Water is used as the reaction mediate. This is the first report of aerobic oxidative bromination using only catalytic amount of metal-free catalyst. This system shows not only high bromine atom economy, but also high bromination selectivity. The possible mechanism and the role of the catalyst in this system have also been discussed.
- Wang, Jian,Chen, Shu-Bin,Wang, Shu-Guang,Li, Jing-Hua
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p. 513 - 517
(2015/03/30)
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- Aerobic oxidative bromination of arenes using an ionic liquid as both the catalyst and the solvent
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A method for the bromination of alkoxy-substituted benzenes and naphthalenes was developed by using the residual oxygen in the reaction tube as the oxidant, and [Bmim]NO3 (1-butyl-3-methylimidazolium nitrate) ionic liquid as both the catalyst and the solvent. No other reagent apart from the ionic liquid and molecular bromine was used in the reactions, and basically all the bromine atoms in the bromine source were transferred to the bromination products, showing that the presented protocol is highly atom economic and practical.
- Ren, Yun-Lai,Wang, Binyu,Tian, Xin-Zhe,Zhao, Shuang,Wang, Jianji
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supporting information
p. 6452 - 6455
(2015/11/16)
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- Total Synthesis of (±)-Taiwaniaquinol F and Related Taiwaniaquinoids
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Total synthesis of (±)-taiwaniaquinol F (1a) has been accomplished via an efficient Lewis acid-catalyzed Nazarov-type cyclization of aryldiallylcarbinols (±)-2e derived from safranal 7. The methodology works under mild conditions using only 2 mol % of met
- Kakde, Badrinath N.,Kumari, Pooja,Bisai, Alakesh
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p. 9889 - 9899
(2015/11/03)
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- Synthesis of deuterated benzopyran derivatives as selective COX-2 inhibitors with improved pharmacokinetic properties
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We designed a series of specifically deuterated benzopyran analogues as new COX-2 inhibitors with the aim of improving their pharmacokinetic properties. As expected, the deuterated compounds retained potency and selectivity for COX-2. The new molecules possess improved pharmacokinetic profiles in rats compared to their nondeuterated congeners. Most importantly, the new compounds showed pharmacodynamic efficacy in several murine models of inflammation and pain. The benzopyran derivatives were separated into their enantiomers, and the activity was found to reside with the S-isomers. To streamline the synthesis of the desired S-isomers, an organocatalytic asymmetric domino oxa-Michael/aldol condensation reaction was developed for their preparation.
- Zhang, Yanmei,Tortorella, Micky D.,Wang, Yican,Liu, Jianqi,Tu, Zhengchao,Liu, Xiaorong,Bai, Yang,Wen, Dingsheng,Lu, Xin,Lu, Yongzhi,Talley, John J.
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p. 1162 - 1166
(2014/12/10)
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- SMALL MOLECULE INHIBITORS OF FIBROSIS
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Described herein are compounds and compositions for the treatment of a fibrotic disease.
- -
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Paragraph 00344
(2015/01/06)
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- Polymer-anchored peroxo compounds of molybdenum and tungsten as efficient and versatile catalysts for mild oxidative bromination
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A polymer supported peroxomolybdate(VI) compound of the type [MoO 2(O2)(CN)2]-PAN [PAN = poly(acrylonitrile)] (PANMo) was obtained by reacting H2MoO4 with 30% H 2O2 and the macromolecular ligand, PAN at near neutral pH. The macrocomplex has been characterized by elemental analysis (CHN and EDX analysis), spectral (IR, UV-Vis and 13C NMR, 95Mo NMR), thermal (TGA-DTG) as well as SEM studies. The catalytic activity of PANMo and its previously reported tungsten containing analog PANW, in oxidative bromination of organic substrates has been explored. The supported complexes could serve as efficient heterogeneous catalysts for the oxidative bromination of a variety of structurally diverse aromatic compounds, with H 2O2 as terminal oxidant, to afford bromo organics in impressive yields under environmentally clean conditions. The catalysts afforded regeneration and could be reused for a minimum of six reaction cycles.
- Boruah, Jeena Jyoti,Das, Siva Prasad,Borah, Rupam,Gogoi, Sandhya Rani,Islam, Nashreen S.
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p. 246 - 254
(2013/05/23)
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- Poly(4-vinylpyridinium bromochromate): An efficient reagent for bromination of aromatic compounds
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A simple and efficient method for the bromination of various aromatic compounds by using poly(4-vinylpyridinium bromochromate) is reported. This method has several advantages such as good selectivity between ortho and para positions of aromatic compounds, simple workup, short reaction times, and high yields of the products.
- Albadi, Jalal,Tajik, Hassan,Keshavarz, Mosadegh,Abedini, Masoumeh
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p. 179 - 181
(2013/07/27)
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- TRIAZOLONE COMPOUNDS AND USES THEREOF
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The invention disclosed herein is directed to compounds of Formula (I) and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention also comprises pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula (I), or a pharmaceutically acceptable salt thereof. The invention disclosed herein is also directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention disclosed herein is further directed to methods of treating prostate, breast, colon, pancreatic, chronic lymphocytic leukemia, melanoma and other cancers comprising administration of a of a therapeutically effective amount of a selective PPARα antagonist. The compounds and pharmaceutical compositions of the invention are also useful in the treatment of viral infections, such as HCV infections and HIV infections. The invention disclosed herein is also directed to a methods of preventing the onset of and/or recurrence of acute and chronic myeloid leukemia, as well as other cancers, comprising administration of a of a therapeutically effective amount of a selective PPARα antagonist.
- -
-
Paragraph 00122; 00126; 00127
(2013/09/26)
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- Simple and improved regioselective brominations of aromatic compounds using N-benzyl-N,N-dimethylanilinium peroxodisulfate in the presence of potassium bromide under mild reactions conditions
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A simple, efficient, and mild method for the selective bromination of some activated aromatic compounds using N-benzyl-N,N-dimethylanilinium peroxodisulfate in the presence of potassium bromide in non-aqueous solution is reported. The results obtained revealed good to excellent selectivity between the ortho and para positions of phenols and methoxyarenes.
- Ghasemnejad-Bosra, Hassan,Ramzanian-Lehmali, Farhad,Jafari, Somaye
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experimental part
p. 685 - 692
(2012/01/16)
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- Oxidative bromination of aromatic compounds using O-iodoxybenzoic acid with tetraethylammonium bromide
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A mild and selective procedure for the bromination of activated arenes using o-iodoxybenzoic acid and tetraethylammonium bromide is presented. The reactions were carried out at room temperature and gave moderate to excellent yields. Copyright Taylor & Francis Group, LLC.
- Bhalerao, Dinesh S.,Mahajan, Ulhas S.,Akamanchi, Krishnacharya G.
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experimental part
p. 2814 - 2819
(2009/04/04)
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- Bromination of some aromatic compounds with potassium bromide in the presence of benzyltriphenylphosphonium peroxodisulfate
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A simple, efficient, and mild method for selective bromination of some activated aromatic compounds using potassium bromide in the presence of benzyltriphenylphosphonium peroxodisulfate in nonaqueous solution is reported. The results obtained revealed good to excellent selectivity between ortho and para positions of phenols and methoxyarenes. Copyright Taylor & Francis Group, LLC.
- Tajik, Hassan,Mohammadpoor-Baltork, Iraj,Albadi, Jalal
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p. 323 - 328
(2007/10/03)
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- A convenient and selective method for the para-bromination of aromatic compounds with potassium bromide in the presence of poly(4-vinylpyridine)- supported peroxodisulfate in nonaqueous solution
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A convenient and selective procedure for the para-bromination of aromatic compounds has been developed using potassium bromide in the presence of poly(4-vinylpyridine)-supported peroxodisulfate in nonaqueous solution.
- Tajik,Mohammadpoor-Baltork,Hassan-Zadeh,Rafiee Rashtabadi
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p. 1282 - 1284
(2008/03/27)
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- De novo asymmetric synthesis of milbemycin β3 via an iterative asymmetric hydration approach
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The enantioselective synthesis of the spiroketal/macrolide natural product milbemycin β3 has been achieved in 22 steps and 2.8% overall yield from an achiral dienoate. The spiroketal ring system was installed by three sequential asymmetric hydr
- Li, Miaosheng,O'Doherty, George A.
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p. 3987 - 3990
(2007/10/03)
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- Bromination of aromatic compounds with potassium bromide in the presence of poly(4-vinylpyridine)-supported bromate in nonaqueous solution
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A simple, efficient, and mild method for selective bromination of activated aromatic compounds using potassium bromide in the presence of poly(4-vinylpyridine)-supported bromate in nonaqueous solution is reported. The results obtained revealed excellent to good selectiveity between ortho and para positions of methoxyarenes, anilines, and phenols. Copyright Taylor & Francis, Inc.
- Tajik, Hassan,Shirini, Farhad,Hassan-Zadeh, Parwin,Rashtabadi, Hassan Rafiee
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p. 1947 - 1952
(2007/10/03)
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- Towards a total synthesis of the new anticancer agent mensacarcin: Synthesis of the carbocyclic core
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A synthesis of the carbocyclic core associated with the new anti-cancer agent mensacarcin (1) is reported. The strategy involves the synthesis of several novel highly substituted aromatic compounds, such as 12 and 23. The lithium derivative of 12 readily
- Tietze, Lutz F.,Stewart, Scott G.,Polomska, Marta E.,Modi, Andrea,Zeeck, Axel
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p. 5233 - 5242
(2007/10/03)
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- Direct and regioselective iodination and bromination of benzene, naphthalene and other activated aromatic compounds using iodine and bromine
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Direct and regioselective iodination and bromination of benzene, naphthalene and other activated aromatic compounds with iodine and bromine or their sodium salts proceed well in the presence of Fe(NO3) 3·1.5N2O4/charcoal in CH 2Cl2 at room temperature.
- Firouzabadi,Iranpoor,Shiri
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p. 8781 - 8785
(2007/10/03)
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- Ionic liquid promoted regioselective monobromination of aromatic substrates with N-bromosuccinimide
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Aromatic substrates were monobrominated regioselectively with NBS in the ionic liquid 1,3-di-n-butylimidazolium tetrafluoroborate [bbim]BF4 in 5 min at 28°C in excellent isolated yields (80-98%) in the absence of a catalyst.
- Rajagopal,Jarikote,Lahoti,Daniel, Thomas,Srinivasan
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p. 1815 - 1817
(2007/10/03)
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- Design of liquid crystalline block molecules with nonconventional mesophase morphologies: Calamitic bolaamphiphiles with lateral alkyl chains
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Novel bolaamphiphiles, consisting of a biphenyl rigid core, polar 2,3-dihydroxypropoxy groups at each terminal end, and an additional long alkyl chain in a lateral position have been synthesized. The structures of these ternary block molecules were systematically changed by variation of the length and position of the alkyl chain, by introduction of additional spacer units between one of the 2,3-dihydroxypropyl groups and the rigid core, and by replacement of one of the 2,3-dihydroxypropoxy groups by a single hydroxy group. The influence of these structural variations on the liquid crystalline properties of these new materials was investigated by polarized-light microscopy, differential scanning calorimetry, and X-ray diffraction. These investigation have shown that, by elongation of the lateral chain, a transition from a smectic monolayer structure (SmA1) via a strongly distorted layer structure (SmA+), a centered rectangular columnar phase (Colr/c2mm) and a noncentered rectangular columnar phase (Colr/p2gg) to a hexagonal columnar phase (Colh/p6mm) takes place. Elongation of the bolaamphiphilic core leads to the loss of the columnar phases, which are replaced by smectic phases, whereas reduction of its length favors the hexagonal columnar phase. This phase sequence is explained as a result of the microsegregation of the lateral alkyl chains from the rigid aromatic cores. The segregated alkyl chains are organized in columns that interrupt the smectic layers. The hydrogen bonding keep the bolaamphiphilic cores fixed end to end, so that they form networks of cylinders around the lipophilic columns. The space required by the alkyl chains with respect to the length of the bolaamphiphilic cores is restricted and largely determines the geometry of the cylinders, which leads to the observed phase sequence. The obtained mesophase morphologies, built up by three distinct sets of subspaces, are related to morphologies of some ternary block copolymers. Furthermore, the investigated compounds represent a novel class of materials, capable of forming supramolecular columnar mesophases.
- Koelbel,Beyersdorff,Xiao Hong Cheng,Tschierske,Kain,Diele
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p. 6809 - 6818
(2007/10/03)
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- Use of methyllithium in metal/halogen exchange; a mild and efficient method for the synthesis of ortho substituted toluenes
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Methyllithium, in the presence of excess methyl iodide, can be used to convert suitably substituted aromatic bromides to the corresponding toluenes under mild conditions and in high yield.
- Andrews,Kitteringham,Voyle
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p. 2323 - 2327
(2007/10/03)
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- Total synthesis of (±)-heliannuol D, an allelochemical from Helianthus annuus
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The total synthesis of (±)-heliannuol D and its epimer has been completed in 9 steps and 12% overall yield from 2-methylanisole. The benzoxepane moiety of the title compound, a common structural feature in the heliannuol family of natural products, is pre
- Vyvyan, James R.,Looper, Ryan E.
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p. 1151 - 1154
(2007/10/03)
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- Environment friendly regiospecific bromination of aromatic ethers by N- bromosuccinimide in presence of montmorillonite
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Reaction of methoxybenzenes and naphthalenes with N-bromosuccinimide in presence of montmorillonite clay (K10) affords excellent yields of regiospecifically brominated products under mild conditions in the absence of solvent.
- Perumal,Vijayabaskar,Gomathi,Selvaraj
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p. 603 - 604
(2007/10/03)
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- Nuclear monobromination of alkyl phenyl ethers with NaClO2, NaBr, Mn(acac)3, and moist silica gel in aprotic solvent
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Nuclear monobromination of aromatic ethers can be achieved with a NaClO2/NaBr/Mn(acac)3 catalyst/silica gel system in dichloromethane in regioselective and high-yielding manner under mild conditions.
- Hirano, Masao,Monobe, Hiroyuki,Yakabe, Shigetaka,Morimoto, Takashi
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p. 1463 - 1470
(2007/10/03)
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- Kaolin-assisted Aromatic Chlorination and Bromination
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Moist kaolin catalyses the regioselective and high-yielding chlorination and bromination of C6H5OR (R = C1-C8 alkyl. Bu1, allyl, cyclohexyl, benzyl) to 4-XC6H4OR (X = Cl and Br, respectively) with NaCl02 and Mn(acac)3 in CH2Cl2 in the absence and presence of NaBr, respectively, under mild and neutral conditions.
- Hirano, Masao,Monobe, Hiroyuki,Yakabe, Shigetaka,Morimoto, Takashi
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p. 662 - 663
(2007/10/03)
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- Electrophilic Aromatic Bromination Using Bromodimethylsulfoniuin Bromide Generated in Situ
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It has been shown that bromodimethylsulfonium bromide, generated in situ by treating dimethyl sulfoxide with aqueous hydrobromic acid, is a milder and more selective reagent for electrophilic aromatic bromination than elemental bromine.
- Majetich, George,Hicks, Rodgers,Reister, Steven
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p. 4321 - 4326
(2007/10/03)
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- Novel terphenyls as selective cyclooxygenase-2 inhibitors and orally active anti-inflammatory agents
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A novel series of terphenyl methyl sulfones and sulfonamides have been shown to be highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. The sulfonamide analogs 17 and 21 were found to be much more potent COX-2 inhibitors and orally active anti-inflammatory agents than the corresponding methyl sulfone analogs 16 and 20, respectively, albeit with some decrease in COX-2 selectivity. Structure-activity relationship studies have determined that incorporation of two fluorine atoms in the central phenyl group, as in 20 and 21, is extremely advantageous for both in vitro COX-2 potency and selectivity as well as in vivo activity. Several noticeable examples in the 1,2-diaryl-4,5-difluorobenzenesulfonamide series are 21a-c,k,l,n (COX-2, IC50 = 0.002-0.004 μM), in which all have in vitro COX-1/COX-2 selectivity > 1000. In addition, sulfonamides 21a,b,d,g,j,m,n,q were shown to have greatly enhanced oral activity with more than 90% inhibition of prostaglandin E2 production in the air pouch model of inflammation. Furthermore, sulfonamide 21b was found to be very active in the rat adjuvant-induced arthritis model (ED50 = 0.05 mg/kg) and carrageenan-induced hyperalgesia assay (ED50 = 38.7 mg/kg) with no indication of gastrointestinal toxicity in rats at doses as high as 200 mg/kg.
- Li, James J.,Norton, Monica B.,Reinhard, Emily J.,Anderson, Gary D.,Gregory, Susan A.,Isakson, Peter C.,Koboldt, Carol M.,Masferrer, Jaime L.,Perkins, William E.,Seibert, Karen,Zhang, Yan,Zweifel, Ben S.,Reitz, David B.
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p. 1846 - 1856
(2007/10/03)
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- A new method for the generation of 5,6-quinolinedione-5-methide: Part V Synthesis of polycyclic heteroaromatics
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Reaction of 6-acetoxy-5-bromomethylquinoline (1c) and 2-bromomethyl-4-(2'-pyridyl)phenyl acetate (2b) with tetrachlorocatechol in acetone in the presence of anhydrous potassium carbonate resulted in the formation of diastereomeric products 3c, 3d, 4e and
- Kasturi, T. R.,Mandal, A. B.,Sridevi, G.
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- A new mild and selective reagent for nuclear bromination
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Hexamethylene tetramine tribromide HMTAHBr3 - a new, mild and regioselective brominant is reported for bromination of aromatic hydrocarbons, substituted ethers, phenols and anilides in high yields.
- Bisarya,Rao
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p. 779 - 788
(2007/10/02)
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- Substituted aminoalkoxybenzene anti-fungicidal compositions and use
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The compound of the formula STR1 wherein each of R1 and R2 individually is hydrogen, lower alkyl or lower alkenyl or together signify straight-chain alkylene with 2 to 4 carbon atoms, R3 is hydrogen, halogen or lower alkyl, Q is alkylene with 4 to 11 carbon atoms and at least 4 carbon atoms between the two free valencies or alkenylene with 4 to 11 carbon atoms and at least 4 carbon atoms between the two free valencies and each of Y and Y' individually is a direct bond or the group --CH2 --, --CH2 CH2 --, --CH=CH-- or --C C--, the group R1 R2 N--Q--O-- is attached to the 3- or 4 -position of ring A and the symbol R designates that the ring to which it is attached is unsubstituted or is substituted with at least one substitutent selected from the group consisting of halogen, trifluoromethyl, cyano, nitro, lower alkyl and lower alkoxy, and their pharmaceutically acceptable acid addition salts can be used for the control or prevention of fungal infections, especially of topical or systemic infections which are caused by pathogenic fungi, and for the manufacture of antifungally-active medicaments. The compounds of formula I have not only a pronounced antifungal activity, but they also exhibit synergistic effects in combination with other known antifungally-active substances which inhibit sterol biosynthesis such as ketoconazole and terbinafine.
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- Diterpenes of Azadirachta indica. Syntheses to confirm structure
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The structure of the diterpene nimbinone 1b has been confirmed by syntheses via a cascade cyclisation and also from podocarpic acid by two separate series of transformations. Synthesis of structure 3b from dehydroabietic acid shows that this does not exhibit the properties described for nimbosodione.
- Burnell,Dumont,Theberge,Desfosses
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p. 2571 - 2578
(2007/10/02)
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- 107. Substitution electrophile aromatique dans l'anhydride sulfureux liquide. Etude cinetique de la reaction de bromination d'anisoles monosubstitues. Transmission des effets electroniques et caracteristiques de l'etat de transition
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Reactivity-structure correlations for anisole and eleven of its substituted derivatives established from bromination rate constants in liquid SO2, unlike observations in water, show the reaction to be highly sensitive to substituent effects, (ρ+H2O = -7.1; ρ+SO2 = -10.51).This result is ascribed to the solvation of the methoxy group which decreases the conjugation of para-substituted (ρ+O = -9.70) compared to that of ortho-substituted derivatives (ρ+p = -8.86).The highly solvated transition state lies far from reactants on the reaction coordinate and the positive charge developed in this state is nearly unity.
- Castellonese, Paul,Villa, Pierre
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p. 1068 - 1077
(2007/10/02)
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- ETUDE CINETIQUE DE LA REACTION DE BROMINATION DANS LE SO2 LIQUIDE. REACTIVITES DU BENZENE, DES POLYMETHYLBENZENES ET D'ANISOLES SUBSTITUES. DETERMINATION DES REACTIVITES RELATIVES ET CALCUL DES FACTEURS DE VITESSE PARTIELLE
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Absolute rate constants for the bromination of a series of anisoles and polymethylbenzenes, have been measured in liquid sulfur dioxide at -23 +/- 2 deg C.Rate constants for benzene and toluene were determined by extrapolation as: 9.6E-7 and 4.2E-4 l mol-1 mn-1 respectively.Under these conditions, the bromination of anisole provides 0.56percent ortho- and 98.99percent para-bromoanisole, and the rate relative to benzene is 6.98E8/1.00.These date lead to the partial rate factors for the methoxy group: οOMef = 1.1E7 and pOMef = 4.12E9.The value mOMef = 1.4 is calculated from the rate constant for p-dimethoxy benzene, 10 l mol-1 mn-1.Similarly, in the case of bromination of toluene, a relative rate of 443/1.00, and an isomer distribution of 16percent ortho- and 84percent para, permit the calculation of partial rate for the methyl group:οMef = 212 mMef = 6.4 pMef = 2232 > correlations log k = f(Σ?+), established for the bromination of anisoles and polymethylbenzenes, exhibit large values for their slopes (ρAnisoles+ = -10.51; ρ+polymethylbenzenes = -9.5), and indicate satisfactory additivity of substituent effects.It appears that the + M effect of the methoxy group is less strong in this solvent than it is in water or acetic acid.Despite its low dielectric constant, (D = 17.5 at -20 deg C), liquid sulfur dioxide appearars to be quite a favourable medium for electrophilic aromatic substitution.Thus, for identical experimental conditions, the rate constants for bromination are 1E2 to 1E4 lower than those observed in water, but 1E3 to 1E5 larger than those in acetic acid.
- Castellonese, Paul,Villa, Pierre
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