- Homogeneous Catalysts Supported on Soluble Polymers: Biphasic Suzuki-Miyaura Coupling of Aryl Chlorides Using Phase-Tagged Palladium-Phosphine Catalysts
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The Suzuki-Miyaura coupling of aryl chlorides and PhB(OH)2 under biphasic conditions (DMSO/heptane) can be performed in almost quantitative yields over several cycles by means of polymeric Pd catalysts with soluble polyethylene glycol phase tags. Three sterically demanding and electron-rich phosphines 1-CH2Br,4-CH2P(1-Ad) 2-C6H4, and 2-PCy2,2′ -OH-biphenyl, and 2-PtBu2,2′-OH-biphenyl were covalently bonded to 2000 Dalton MeOPEG-OH. The catalysts, which were formed in situ from Na2[PdCl4], the respective polymeric phosphine, KF/K 3PO4, and PhB(OH)2, efficiently couple aryl chlorides at 80°C at 0.5 mol% loading, resulting in a > 90% yield of the respective biphenyl derivatives. The use of polar phase tags allows the efficient recovery of palladium-phosphine catalysts by simple phase separation of the catalyst-containing DMSO solution and the product-containing n-heptane phase. The high activity (TOF) of the catalyst remains almost constant over more than five reaction cycles, which involve the catalytic reaction, separation of the product phase from the catalyst phase, and addition of new reactants to initiate the next cycle. The Buchwald type biphenyl phosphines form the most active Pd catalysts, which are 1.3-2.8 times more active than catalysts derived from diadamantyl-benzylphosphine, but appear to be less robust in the recycling experiments. There is no apparent leaching of the catalyst into the heptane solution ( 0.05%), as evidenced by spectrophotometric measurements, and contamination of the product with Pd is avoided.
- An Der Heiden, Markus,Plenio, Herbert
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- Studies on Pd/NiFe2O4 catalyzed ligand-free Suzuki reaction in aqueous phase: Synthesis of biaryls, terphenyls and polyaryls
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Palladium supported on nickel ferrite (Pd/NiF2O4) was found to be a highly active catalyst for the Suzuki coupling reaction between various aryl halides and arylboronic acids. The reaction gave excellent yields (70-98%) under ligand free conditions in a 1:1 DMF/H2O solvent mixture, in short reaction times (10-60 min). The catalyst could be recovered easily by applying an external magnetic field. The polyaryls were similarly synthesized.
- Borhade, Sanjay R.,Waghmode, Suresh B.
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- Identification and Optimization of Novel Small-Molecule Cas9 Inhibitors by Cell-Based High-Throughput Screening
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CRISPR/Cas9 has revolutionized several areas of life science; however, methods to control the Cas9 activity are needed for both scientific and therapeutic applications. Anti-CRISPR proteins are known to inhibit the CRISPR/Cas adaptive immunity; however, in vivo delivery of such proteins is problematic. Instead, small-molecule Cas9 inhibitors could serve as useful tools due to their permeable, proteolytically stable, and non-immunogenic nature. Here, we identified a small-molecule ligand with anti-CRISPR/Cas9 activity through a high-throughput screening utilizing an Escherichia coli selection system. Extensive structure-activity relationship studies, which involved a deconstruction-reconstruction strategy, resulted in a range of analogues with significant improvements in the inhibitory activity. Based on NMR and electrophoretic mobility shift assays, we propose that the inhibitory action of these compounds likely results from direct binding to apo-Cas9, preventing Cas9:gRNA complex formation. These molecules may find use as Cas9 modulators in various applications.
- Lee, Sang-Woo,Tran, Kim Tai,Vazquez-Uribe, Ruben,Gotfredsen, Charlotte Held,Clausen, Mads Hartvig,Mendez, Blanca Lopez,Montoya, Guillermo,Bach, Anders,Sommer, Morten Otto Alexander
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p. 3266 - 3305
(2022/02/23)
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- 4-Alkyl-1,2,4-triazole-3-thione analogues as metallo-β-lactamase inhibitors
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In Gram-negative bacteria, the major mechanism of resistance to β-lactam antibiotics is the production of one or several β-lactamases (BLs), including the highly worrying carbapenemases. Whereas inhibitors of these enzymes were recently marketed, they only target serine-carbapenemases (e.g. KPC-type), and no clinically useful inhibitor is available yet to neutralize the class of metallo-β-lactamases (MBLs). We are developing compounds based on the 1,2,4-triazole-3-thione scaffold, which binds to the di-zinc catalytic site of MBLs in an original fashion, and we previously reported its promising potential to yield broad-spectrum inhibitors. However, up to now only moderate antibiotic potentiation could be observed in microbiological assays and further exploration was needed to improve outer membrane penetration. Here, we synthesized and characterized a series of compounds possessing a diversely functionalized alkyl chain at the 4-position of the heterocycle. We found that the presence of a carboxylic group at the extremity of an alkyl chain yielded potent inhibitors of VIM-type enzymes with Ki values in the μM to sub-μM range, and that this alkyl chain had to be longer or equal to a propyl chain. This result confirmed the importance of a carboxylic function on the 4-substituent of 1,2,4-triazole-3-thione heterocycle. As observed in previous series, active compounds also preferentially contained phenyl, 2-hydroxy-5-methoxyphenyl, naphth-2-yl or m-biphenyl at position 5. However, none efficiently inhibited NDM-1 or IMP-1. Microbiological study on VIM-2-producing E. coli strains and on VIM-1/VIM-4-producing multidrug-resistant K. pneumoniae clinical isolates gave promising results, suggesting that the 1,2,4-triazole-3-thione scaffold worth continuing exploration to further improve penetration. Finally, docking experiments were performed to study the binding mode of alkanoic analogues in the active site of VIM-2.
- Gavara, Laurent,Legru, Alice,Verdirosa, Federica,Sevaille, Laurent,Nauton, Lionel,Corsica, Giuseppina,Mercuri, Paola Sandra,Sannio, Filomena,Feller, Georges,Coulon, Rémi,De Luca, Filomena,Cerboni, Giulia,Tanfoni, Silvia,Chelini, Giulia,Galleni, Moreno,Docquier, Jean-Denis,Hernandez, Jean-Fran?ois
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supporting information
(2021/06/15)
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- 1,2,4-Triazole-3-thione compounds with a 4-ethyl alkyl/aryl sulfide substituent are broad-spectrum metallo-β-lactamase inhibitors with re-sensitization activity
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Metallo-β-lactamases (MBLs) are important contributors of Gram-negative bacteria resistance to β-lactam antibiotics. MBLs are highly worrying because of their carbapenemase activity, their rapid spread in major human opportunistic pathogens while no clinically useful inhibitor is available yet. In this context, we are exploring the potential of compounds based on the 1,2,4-triazole-3-thione scaffold as an original ligand of the di-zinc active sites of MBLs, and diversely substituted at its positions 4 and 5. Here, we present a new series of compounds substituted at the 4-position by a thioether-containing alkyl chain with a carboxylic and/or an aryl group at its extremity. Several compounds showed broad-spectrum inhibition with Ki values in the μM to sub-μM range against VIM-type enzymes, NDM-1 and IMP-1. The presence of the sulfur and of the aryl group was important for the inhibitory activity and the binding mode of a few compounds in VIM-2 was revealed by X-ray crystallography. Importantly, in vitro antibacterial susceptibility assays showed that several inhibitors were able to potentiate the activity of meropenem on Klebsiella pneumoniae clinical isolates producing VIM-1 or VIM-4, with a potentiation effect of up to 16-fold. Finally, a selected compound was found to only moderately inhibit the di-zinc human glyoxalase II, and several showed no or only moderate toxicity toward several human cells, thus favourably completing a promising behaviour.
- Becker, Katja,Benvenuti, Manuela,Bossis, Guillaume,Conde, Pierre-Alexis,Crowder, Michael W.,Dillenberger, Melissa,Docquier, Jean-Denis,Gavara, Laurent,Hernandez, Jean-Fran?ois,Legru, Alice,Mangani, Stefano,Pozzi, Cecilia,Sannio, Filomena,Tassone, Giusy,Thomas, Caitlyn A.,Verdirosa, Federica
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supporting information
(2021/10/12)
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- 4-Amino-1,2,4-triazole-3-thione-derived Schiff bases as metallo-β-lactamase inhibitors
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Resistance to β-lactam antibiotics in Gram-negatives producing metallo-β-lactamases (MBLs) represents a major medical threat and there is an extremely urgent need to develop clinically useful inhibitors. We previously reported the original binding mode of 5-substituted-4-amino/H-1,2,4-triazole-3-thione compounds in the catalytic site of an MBL. Moreover, we showed that, although moderately potent, they represented a promising basis for the development of broad-spectrum MBL inhibitors. Here, we synthesized and characterized a large number of 4-amino-1,2,4-triazole-3-thione-derived Schiff bases. Compared to the previous series, the presence of an aryl moiety at position 4 afforded an average 10-fold increase in potency. Among 90 synthetic compounds, more than half inhibited at least one of the six tested MBLs (L1, VIM-4, VIM-2, NDM-1, IMP-1, CphA) with Ki values in the μM to sub-μM range. Several were broad-spectrum inhibitors, also inhibiting the most clinically relevant VIM-2 and NDM-1. Active compounds generally contained halogenated, bicyclic aryl or phenolic moieties at position 5, and one substituent among o-benzoic, 2,4-dihydroxyphenyl, p-benzyloxyphenyl or 3-(m-benzoyl)-phenyl at position 4. The crystallographic structure of VIM-2 in complex with an inhibitor showed the expected binding between the triazole-thione moiety and the dinuclear centre and also revealed a network of interactions involving Phe61, Tyr67, Trp87 and the conserved Asn233. Microbiological analysis suggested that the potentiation activity of the compounds was limited by poor outer membrane penetration or efflux. This was supported by the ability of one compound to restore the susceptibility of an NDM-1-producing E. coli clinical strain toward several β-lactams in the presence only of a sub-inhibitory concentration of colistin, a permeabilizing agent. Finally, some compounds were tested against the structurally similar di-zinc human glyoxalase II and found weaker inhibitors of the latter enzyme, thus showing a promising selectivity towards MBLs.
- Baud, Damien,Bebrone, Carine,Becker, Katja,Benvenuti, Manuela,Cerboni, Giulia,Chelini, Giulia,Cutolo, Giuliano,De Luca, Filomena,Docquier, Jean-Denis,Feller, Georges,Fischer, Marina,Galleni, Moreno,Gavara, Laurent,Gresh, Nohad,Kwapien, Karolina,Legru, Alice,Mangani, Stefano,Mercuri, Paola,Pozzi, Cecilia,Sannio, Filomena,Sevaille, Laurent,Tanfoni, Silvia,Verdirosa, Federica,Berthomieu, Dorothée,Bestgen, Beno?t,Frère, Jean-Marie,Hernandez, Jean-Fran?ois
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supporting information
(2020/09/16)
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- Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL)
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High serum fatty acid (FA) levels are causally linked to the development of insulin resistance, which eventually progresses to type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) generalized in the term metabolic syndrome. Adipose triglyceride lipase (ATGL) is the initial enzyme in the hydrolysis of intracellular triacylglycerol (TG) stores, liberating fatty acids that are released from adipocytes into the circulation. Hence, ATGL-specific inhibitors have the potential to lower circulating FA concentrations, and counteract the development of insulin resistance and NAFLD. In this article, we report about structure–activity relationship (SAR) studies of small molecule inhibitors of murine ATGL which led to the development of Atglistatin. Atglistatin is a specific inhibitor of murine ATGL, which has proven useful for the validation of ATGL as a potential drug target.
- Breinbauer, Rolf,Doler, Carina,Fuchs, Elisabeth,Grabner, Gernot F.,Mayer, Nicole,Melcher, Michaela-Christina,Migglautsch, Anna K.,Romauch, Matthias,Schweiger, Martina,Zechner, Rudolf,Zimmermann, Robert
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supporting information
(2020/07/13)
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- Base-free Pd-MOF catalyzed the Suzuki-Miyaura cross-coupling reaction of arenediazonium tetrafluoroborate salts with arylboronic acids
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A convenient and environmental benign synthesis of biaryls has been demonstrated by a straightforward reaction catalyzed by the palladium-containing metal-organic framework (Pd-MOF) [Pd (2-pymo)2]n (2-pymo = 2-pyrimidinolate). A series of functionalized biaryl derivatives have been synthesized in good to excellent yields by the Suzuki-miyaura cross-couplings of sustainable arenediazonium salts with a variety of arylboronic acids and the reactions were catalyzed by the Pd-MOF using methanol as a benign solvent. Those base- and additive-free catalytic reactions proceeded smoothly under non-anhydrous and non-degassed condition. Such transformation avoided high reaction temperature, tolerated many functional groups and presented a wide substrate scope. The catalyst could be recovered by filtration and reused for four successive cycles before collapse of the MOF structure.
- Liu, Yangyang,Wang, Jie,Li, Tang,Zhao, Zesheng,Pang, Wan
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- Electron-Catalyzed Cross-Coupling of Arylboron Compounds with Aryl Iodides
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Arylboroxines in combination with zinc chloride and potassium tert-butoxide were found to undergo the electron-catalyzed cross-coupling with aryl iodides to give the corresponding biaryls without the aid of transition-metal catalysis.
- Okura, Keisho,Teranishi, Tsuyoshi,Yoshida, Yuto,Shirakawa, Eiji
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supporting information
p. 7186 - 7190
(2018/06/15)
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- 1,2,4-Triazole-3-thione Compounds as Inhibitors of Dizinc Metallo-β-lactamases
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Metallo-β-lactamases (MBLs) cause resistance of Gram-negative bacteria to β-lactam antibiotics and are of serious concern, because they can inactivate the last-resort carbapenems and because MBL inhibitors of clinical value are still lacking. We previously identified the original binding mode of 4-amino-2,4-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione (compound IIIA) within the dizinc active site of the L1 MBL. Herein we present the crystallographic structure of a complex of L1 with the corresponding non-amino compound IIIB (1,2-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione). Unexpectedly, the binding mode of IIIB was similar but reverse to that of IIIA. The 3 D structures suggested that the triazole–thione scaffold was suitable to bind to the catalytic site of dizinc metalloenzymes. On the basis of these results, we synthesized 54 analogues of IIIA or IIIB. Nineteen showed IC50 values in the micromolar range toward at least one of five representative MBLs (i.e., L1, VIM-4, VIM-2, NDM-1, and IMP-1). Five of these exhibited a significant inhibition of at least four enzymes, including NDM-1, VIM-2, and IMP-1. Active compounds mainly featured either halogen or bulky bicyclic aryl substituents. Finally, some compounds were also tested on several microbial dinuclear zinc-dependent hydrolases belonging to the MBL-fold superfamily (i.e., endonucleases and glyoxalase II) to explore their activity toward structurally similar but functionally distinct enzymes. Whereas the bacterial tRNases were not inhibited, the best IC50 values toward plasmodial glyoxalase II were in the 10 μm range.
- Sevaille, Laurent,Gavara, Laurent,Bebrone, Carine,De Luca, Filomena,Nauton, Lionel,Achard, Maud,Mercuri, Paola,Tanfoni, Silvia,Borgianni, Luisa,Guyon, Carole,Lonjon, Pauline,Turan-Zitouni, Gülhan,Dzieciolowski, Julia,Becker, Katja,Bénard, Lionel,Condon, Ciaran,Maillard, Ludovic,Martinez, Jean,Frère, Jean-Marie,Dideberg, Otto,Galleni, Moreno,Docquier, Jean-Denis,Hernandez, Jean-Fran?ois
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p. 972 - 985
(2017/06/27)
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- Cyanoborohydride-promoted radical arylation of benzene
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Radical biaryl coupling of iodoarenes and benzene can be effectively promoted by tetrabutylammonium cyanoborohydride with air under photoirradiation conditions using a Xe lamp. The utility of this methodology is highlighted by its functional group tolerance and chemoselectivity.
- Kawamoto, Takuji,Sato, Aoi,Ryu, Ilhyong
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supporting information
p. 2111 - 2113
(2014/05/06)
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- N-Heterocyclic carbene/phosphite synergistically assisted Pd/C-catalyzed Suzuki coupling of aryl chlorides
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An N-heterocyclic carbene and phosphite synergistically enhanced Pd/C catalyst system has been developed for Suzuki coupling of aryl chlorides and aryl boronic acids from commercially available Pd/C with sterically demanding N,N′-bis(2,6-diisopropylphenyl)imidazolylidene and trimethylphosphite. A remarkable increase in catalytic activity of Pd/C was observed when used along with 1 equiv. N,N′-bis(2,6-diisopropylphenyl)imidazolium chloride and 2 equiv. phosphite with respect to palladium in appropriate solvents that were found to play a crucial role in Pd/C-NHC-P(OR)3-catalyzed Suzuki coupling. A dramatic ortho-substitution effect of carbonyl and nitrile groups in aryl chlorides was observed and explained by a modified quasi-heterogeneous catalysis mechanism. The Pd/C catalyst could be easily recovered from reaction mixtures by simple filtration and only low palladium contamination was detected in the biparyl products. A practical process for the synthesis of 4-biphenylcarbonitrile has therefore been developed using the N-heterocyclic carbene/phosphite-assisted Pd/C-catalyzed Suzuki coupling. Copyright
- Ke, Haihua,Chen, Xiaofeng,Zou, Gang
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- Copolymer-incarcerated nickel nanoparticles with N-heterocyclic carbene precursors as active cross-linking agents for Corriu-Kumada-Tamao reaction
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We have developed heterogeneous polymer-incarcerated nickel nanoparticles (NPs), which catalyze cross-coupling reactions. The matrix structure of these catalysts incorporates both N-heterocyclic carbenes (NHCs) as ligands and Ni-NPs, thanks to a new design of cross-linking agents in polymer supports. These embedded NHCs were detected by field gradient swollen-resin magic angle spinning NMR analysis. They were successfully applied to Corriu-Kumada-Tamao reactions with a broad substrate scope including functional group tolerance, and the catalyst could be recovered and reused several times without loss of activity.
- Soule, Jean-Francois,Miyamura, Hiroyuki,Kobayashi, Shu
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supporting information
p. 10602 - 10605
(2013/08/23)
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- Synthesis of pinacol arylboronates from aromatic amines: A metal-free transformation
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A metal-free borylation process based on Sandmeyer-type transformation using arylamines derivatives as the substrates has been developed. Through optimization of the reaction conditions, this novel conversion can be successfully applied to a wide range of aromatic amines, affording borylation products in moderate to good yields. Various functionalized arylboronates, which are difficult to access by other methods, can be easily obtained with this metal-free transformation. Moreover, this transformation can be followed by Suzuki-Miyaura cross-coupling without purification of the borylation products, which enhances the practical usefulness of this method. A possible reaction mechanism involving radical species has been proposed.
- Qiu, Di,Jin, Liang,Zheng, Zhitong,Meng, He,Mo, Fanyang,Wang, Xi,Zhang, Yan,Wang, Jianbo
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p. 1923 - 1933
(2013/03/29)
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- Palladium(II)-exchanged hydroxyapatite-catalyzed Suzuki-Miyaura-type cross-coupling reactions with potassium aryltrifluoroborates
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Palladium(II)-exchanged hydroxyapatite (PdHAP; Pd/Ca ratio = ca. 1/200) was prepared by ion-exchanging with Ca2+ from calcined hydroxyapatite (2.0 mmol) and Pd(NO3)2 (0.10 mmol) in water (150 mL) at 70 °C for 24 h. The PdHAP (1 mol% Pd to aryl bromides) functioned as a catalyst for the Suzuki-Miyaura-type cross-coupling reaction of aryl bromides and potassium aryltrifluoroborates with triphenylphosphine (1 mol%) and excess potassium carbonate at 50 °C in methanol under air. This cross-coupling reaction was found to proceed in water, while the rate was slow compared with that in methanol. The heterogeneous PdHAP catalyst was used ten times repeatedly at 50 °C in methanol under air, though its catalytic activity gradually declined. XRD and XRF analyses and TEM images revealed that most of palladium species would still be supported as isolated ions on the repeatedly used PdHAP, in spite of the changes of the structure and composition of PdHAP surface at the late stages in the repetitive uses and the partial leaching of Pd species at the initial stages in the repetitive uses. The gradual decline of the catalytic activity might be dependent on either the changes of PdHAP surface at the late stages or the partial leaching of Pd species at the initial stages. Still, heterogeneous PdHAP served as a reusable catalyst for Suzuki-Miyaura-type cross-coupling reaction with potassium aryltrifluoroborates.
- Masuyama, Yoshiro,Sugioka, Yutaka,Chonan, Shiori,Suzuki, Noriyuki,Fujita, Masahiro,Hara, Kenji,Fukuoka, Atsushi
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experimental part
p. 81 - 85
(2012/02/03)
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- ORGANOMETALLIC COMPLEX, LIGHT-EMITTING ELEMENT, DISPLAY DEVICE, ELECTRONIC DEVICE, AND LIGHTING DEVICE
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Provided are organometallic complexes that can exhibit phosphorescence. One of the novel organometallic complexes is represented by General Formula (G1). In General Formula (G1), R1 represents any of an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms which may have a substituent, and an aralkyl group having 7 to 10 carbon atoms which may have a substituent. In addition, R2 represents any of an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms which may have a substituent, and an aryl group having 6 to 12 carbon atoms which may have a substituent. Further, Ar represents an arylene group having 6 to 13 carbon atoms which may have a substituent. Further, M represents a Group 9 element or a Group 10 element.
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Page/Page column 150-151
(2011/05/11)
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- Studies on phosphine free Pd-salen complexes as effective catalysts for aqueous Suzuki reaction
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Palladium complexes of the salen ligands, N,N'-bis(salicylidene)- ethylenediamine and N,N'-bis(salicylidene)-1,.-phenylenediamine have been explored for their catalytic activity in a phosphine-free aqueous Suzuki reaction. The various reaction parameters have been systematically optimized with respect to various solvents, bases, temperatures and Pd concentrations. The studies conclude that 1:1 DMF to water solvent ratio, Na2CO 3 as base and 0.5 mo1% of palladium at 90°C is apt for Suzuki reactions. Rapid transformation of substituted aryl iodides and aryl bromides into corresponding biaryls has been observed with excellent yield ranging from 70-86%, under optimized conditions.
- Borhade, Sanjay R.,Waghmode, Suresh B.
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experimental part
p. 565 - 572
(2010/12/25)
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- Preparation of unsymmetrical biaryls by pd(II)-catalyzed cross-coupling of aryl iodides
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The Ullmann homo-and cross-couplings of aryl iodides are carried out to afford symmetrical and unsymmetrical biaryls in moderate to good yields in a catalytic system of Pd(OAc)2/K2CO3/MeCOEt. The high selectivity of unsymmetrical biaryl products in cross-couplings mainly depends on the reactivity difference between two iodoarene substrates and their employed ratios.
- Wang, Liqiang,Lu, Wenjun
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supporting information; experimental part
p. 1079 - 1082
(2009/07/25)
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- Efficient cobalt-catalyzed formation of unsymmetrical biaryl compounds and its application in the synthesis of a sartan intermediate
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(Chemical Equation Presented) No prior preparation of the organometallic reagent is required in a cobalt-catalyzed coupling of two different aryl halides under mild conditions (see scheme). A broad spectrum of valuable biaryl compounds can be prepared in this way. Not only may a variety of reactive substituents be present, but heteroaryl halides and aryl triflates are also suitable substrates. DMF = N,N-dimethylformamide, FG = functional group.
- Amatore, Muriel,Gosmini, Corinne
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supporting information; experimental part
p. 2089 - 2092
(2009/02/06)
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- IRON OR COBALT-CATALYZED CARBON-CARBON COUPLING REACTION OF ARYLS, ALKENES AND ALKINES WITH COPPER REAGENTS
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The invention relates to a method for combining carbon-carbon bonds starting from a copper compound of an aryl, heteroaryl, alkene or alkine and an aryl, heteroaryl, alkene or alkine compound with a suitable nucleofuge. The copper compounds can be produced inter alia by transmetallization from a Gignard or lithium compound. The cross-coupling of said compounds is carried out with a halogen-substituted aryl compound with the aid of an iron or cobalt catalyst using a suitable solvent and suitable additives.
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Page/Page column 8
(2010/11/08)
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- Radical additions of aryl iodides to arenes are facilitated by oxidative rearomatization with dioxygen
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Inter- and intramolecular additions of aryl radicals derived from aryl iodides to arenes are promoted by tris(trimethylsilyl)silane and occur under exceptionally mild conditions (15-30 min at 25 °C) in nondegassed benzene. A chain mechanism involving reaction of the intermediate cyclohexadienyl radical with oxygen to directly generate the aromatized product and the hydroperoxy radical is proposed. Copyright
- Curran, Dennis P.,Keller, Adam I.
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p. 13706 - 13707
(2007/10/03)
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- Iron-catalyzed aryl-aryl cross-couplings with magnesium-derived copper reagents
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(Chemical Equation Presented) Well-matched couples: Functionalized aryl and heteroaryl copper species obtained from the corresponding magnesium derivatives undergo Fe-catalyzed cross-coupling reactions with aryl iodides that bear keto, ester, triflate, or nitrile groups (see scheme).
- Sapountzis, Ioannis,Lin, Wenwei,Kofink, Christiane C.,Despotopoulou, Christina,Knochel, Paul
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p. 1654 - 1657
(2007/10/03)
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- Versatile palladium-catalyzed arylation of organomanganese chlorides by aryl bromides
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In THF, a palladium-catalyzed cross-coupling reaction of organomanganese reagents with various aryl bromides including unreactive deactivated or hindered aryl bromides was performed successfully in the presence of a new catalytic system 1% PdCl2(dppp)-four equivalents DME. The scope of the reaction is very broad since many functional groups are tolerated, moreover, even hindered O,O′-di- or trisubstituted diaryls were obtained in high yields. It is interesting to note that hindered aryl bromides are more reactive than the corresponding aryl iodides. Alkyl, alkenyl and alkynylmanganese chlorides also react under similar conditions.
- Riguet, Eric,Alami, Mouad,Cahiez, Gérard
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p. 376 - 379
(2007/10/03)
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- Derivatives of aminobenzoic and aminobiphenylcarboxylic acids useful as anti-cancer agents
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The present invention provides compounds having the formula: wherein n is0or1; R is —NH2or wherein R1and R2are independently selected from the group consisting of H, alkyl, aralkyl, heteroaralkyl, carboxy, carboxyalkyl, and carbamoyl; Q is R3C(O)— or wherein R5is selected from the group consisting of H, alkyl, aralkyl, heteroaralkyl, and carbamoylalkyl, and R3and R4are selected from the group consisting of H, alkyl, alkoxy, arylalkoxy, aralkyl, heteroaralkyl, and carbamoylalkyl; the Q—NH—(CH2)n— and the —C(O)R substituents of the compound of formula I are independently positioned ortho, meta, orpara relative to the carbon atoms that form the bond between the two phenyl groups to which said substituents are bound, with the proviso that said substituents are not both positioned ortho; and the Q—NH—(CH2)nand the —C(O)R substituents of the compound of formula II are positioned meta orpara to each other; or a biolabile ester thereof, or a pharmaceutically acceptable salt thereof. The compounds are useful for treating uPA- or uPAR-mediated disorders, e.g., tumor metastasis, tumor angiogenesis, restenosis, chronic inflammation, or corneal angiogenesis.
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- Nonpeptide arginine vasopressin antagonists for both V(1A) and V2 receptors: Synthesis and pharmacological properties of 2-Phenyl-4'- [(2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]benzanilide derivatives
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A series of compounds structurally related to 4'-[(2,3,4,5-tetrahydro- 1H-1-benzazepin-1-yl)carbonyl]benzanilide was synthesized and demonstrated to have arginine vasopressin (AVP) antagonist activity for both V(1A) and V2 receptors. The introduction of a phenyl or a 4-substituted phenyl group into the ortho position of the benzoyl moiety resulted in an increase in both binding affinity and antagonistic activity. The 2-(4-methylphenyl) derivative (1g) exhibited high antagonistic activities for both V(1A) (8.6- fold) and V2 (38-fold) receptors and high oral activity (8.6-fold) compared with the 2-methyl lead compound (1a). Detail of the synthesis and the pharmacological properties of this series are presented.
- Matsuhisa, Akira,Tanaka, Akihiro,Kikuchi, Kazumi,Shimada, Yoshiaki,Yatsu, Takeyuki,Yanagisawa, Isao
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p. 1870 - 1874
(2007/10/03)
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