- 2,2'-Biindolyl revisited. Synthesis and reactions
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An improved synthesis of 2,2'-biindolyl (1) is described. Derivatives of 1 with a variety of substituents in the 3,3'-positions, such as the 3,3'-diformyl derivative 19 have been synthesized. Potential syntheses of indolocarbazole alkaloids from such deri
- Bergman,Koch,Pelcman
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- Engineering Boron Hot Spots for the Site-Selective Installation of Iminoboronates on Peptide Chains
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Boronic acids (BAs) are a promising bioconjugation function to design dynamic materials as they can establish reversible covalent bonds with oxygen/nitrogen nucleophiles that respond to different pH, ROS, carbohydrates and glutathione levels. However, the dynamic nature of these bonds also limits the control over the stability and site-selectivity of the bioconjugation, which ultimately leads to heterogeneous conjugates with poor stability under physiological conditions. Here we disclose a new strategy to install BAs on peptide chains. In this study, a “boron hot spot“ based on the 3-hydroxyquinolin-2(1H)-one scaffold was developed and upon installation on a peptide N-terminal cysteine, enables the site-selective formation of iminoboronates with 2-formyl-phenyl boronic acids (Ka of 58128±2 m?1). The reaction is selective in the presence of competing lysine ?-amino groups, and the resulting iminoboronates, displayed improved stability in buffers solutions and a cleavable profile in the presence of glutathione. Once developed, the methodology was used to prepare cleavable fluorescent conjugates with a laminin fragment, which enabled the validation of the 67LR receptor as a target to deliver cargo to cancer HT29 cells.
- Russo, Roberto,Padanha, Rita,Fernandes, Fábio,Veiros, Luis F.,Corzana, Francisco,Gois, Pedro M. P.
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supporting information
p. 15226 - 15231
(2020/10/20)
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- Enantioselective Intermolecular Excited-State Photoreactions Using a Chiral Ir Triplet Sensitizer: Separating Association from Energy Transfer in Asymmetric Photocatalysis
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Enantioselective catalysis of excited-state photoreactions remains a substantial challenge in synthetic chemistry, and intermolecular photoreactions have proven especially difficult to conduct in a stereocontrolled fashion. Herein, we report a highly enantioselective intermolecular [2 + 2] cycloaddition of 3-alkoxyquinolones catalyzed by a chiral hydrogen-bonding iridium photosensitizer. Enantioselectivities as high as 99% ee were measured in reactions with a range of maleimides and other electron-deficient alkene reaction partners. An array of kinetic, spectroscopic, and computational studies supports a mechanism in which the photocatalyst and quinolone form a hydrogen-bonded complex to control selectivity, yet upon photoexcitation of this complex, energy transfer sensitization of maleimide is preferred. The sensitized maleimide then reacts with the hydrogen-bonded quinolone-photocatalyst complex to afford a highly enantioenriched cycloadduct. This finding contradicts a long-standing tenet of enantioselective photochemistry that held that stereoselective photoreactions require strong preassociation to the sensitized substrate in order to overcome the short lifetimes of electronically excited organic molecules. This system therefore suggests that a broader range of alternate design strategies for asymmetric photocatalysis might be possible.
- Zheng, Jian,Swords, Wesley B.,Jung, Hoimin,Skubi, Kazimer L.,Kidd, Jesse B.,Meyer, Gerald J.,Baik, Mu-Hyun,Yoon, Tehshik P.
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p. 13625 - 13634
(2019/08/26)
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- Enantioselective Excited-State Photoreactions Controlled by a Chiral Hydrogen-Bonding Iridium Sensitizer
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Stereochemical control of electronically excited states is a long-standing challenge in photochemical synthesis, and few catalytic systems that produce high enantioselectivities in triplet-state photoreactions are known. We report herein an exceptionally effective chiral photocatalyst that recruits prochiral quinolones using a series of hydrogen-bonding and π-π interactions. The organization of these substrates within the chiral environment of the transition-metal photosensitizer leads to efficient Dexter energy transfer and effective stereoinduction. The relative insensitivity of these organometallic chromophores toward ligand modification enables the optimization of this catalyst structure for high enantiomeric excess at catalyst loadings as much as 100-fold lower than the optimal conditions reported for analogous chiral organic photosensitizers.
- Skubi, Kazimer L.,Kidd, Jesse B.,Jung, Hoimin,Guzei, Ilia A.,Baik, Mu-Hyun,Yoon, Tehshik P.
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p. 17186 - 17192
(2017/12/06)
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- Enantioselective, intermolecular [2+2] photocycloaddition reactions of 3-acetoxyquinolone: Total synthesis of (-)-pinolinone
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The natural product (-)-pinolinone was synthesised via a concise route (six steps, 17% overall yield) from 3-acetoxyquinolone, employing an enantioselective intermolecular [2+2] photocycloaddition as the key step. The Royal Society of Chemistry 2014.
- Mayr, Florian,Wiegand, Christian,Bach, Thorsten
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supporting information
p. 3353 - 3355
(2014/03/21)
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- THERAPEUTIC HYDROXYQUINOLONES
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The invention provides compounds of formula (I) and salts thereof wherein R4-R8 have any of the meanings defined in the specification, as well as pharmaceutical compositions comprising the compounds or salts and methods for their use in therapy. The compounds have useful antiviral properties.
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Page/Page column 34
(2014/05/24)
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- Pinacol rearrangement of 3,4-dihydro-3,4-dihydroxyquinolin-2(1H)-ones: An alternative pathway to viridicatin alkaloids and their analogs
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3-Alkyl/aryl-3-hydroxyquinoline-2,4-diones were reduced with NaBH 4 to give cis-3-alkyl/aryl-3,4-dihydro-3,4-dihydroxyquinolin-2(1H)- ones. These compounds were subjected to pinacol rearrangement by treatment with concentrated H2SOs
- Rudolf, Ondrej,Rouchal, Michal,Lycka, Antonin,Klasek, Antonin
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p. 1905 - 1917
(2013/11/06)
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- 3-Hydroxyquinolin-2(1H)-ones as inhibitors of influenza A endonuclease
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Several 3-hydroxyquinolin-2(1H)-ones derivatives were synthesized and evaluated as inhibitors of 2009 pandemic H1N1 influenza A endonuclease. All five of the monobrominated 3-hydroxyquinolin(1H)-2-ones derivatives were synthesized. Suzuki-coupling of p-fluorophenylboronic acid with each of these brominated derivatives provided the respective p-fluorophenyl 3-hydroxyquinolin(1H)-2-ones. In addition to 3-hydroxyquinolin-2(1H)-one, its 4-methyl, 4-phenyl, 4-methyl-7-(p-fluorophenyl), and 4-phenyl-7-(p-fluorophenyl) derivatives were also synthesized. Comparative studies on their relative activity revealed that both 6- and 7-(p-fluorophenyl)-3-hydroxyquinolin-2(1H)- one are among the more potent inhibitors of H1N1 influenza A endonuclease. An X-ray crystal structure of 7-(p-fluorophenyl)-3-hydroxyquinolin-2(1H)-one complexed to the influenza endonuclease revealed that this molecule chelates to two metal ions at the active site of the enzyme.
- Sagong, Hye Yeon,Parhi, Ajit,Bauman, Joseph D.,Patel, Disha,Vijayan,Das, Kalyan,Arnold, Eddy,LaVoie, Edmond J.
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supporting information
p. 547 - 550
(2013/07/26)
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- Ring-expansion reaction of isatins with ethyl diazoacetate catalyzed by dirhodium(II)/DBU metal-organic system: En route to viridicatin alkaloids
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We present here the NHC-dirhodium(II)/DBU-catalyzed ring expansion reaction of isatins with ethyl diazoacetate. This new one-pot protocol yields the ethyl 3-hydroxy-2(1H)-oxoquinoline-4-carboxylate core, regioselectively and in good to excellent yields. A DFT mechanistic study indicates metallocarbene formation between the 3-hydroxyindole-diazo intermediate and the dirhodium(II) complex to be the rate-limiting step of the reaction. The synthesized ethyl 3-hydroxy-2(1H)-oxoquinoline-4-carboxylate core could be readily converted to viridicatin alkaloids, in yields up to 80 % by a microwave-assisted Suzuki-Miyaura cross coupling of the 3-hydroxy-4-bromoquinolin-2(1H)-one with arylboronic acid. Copyright
- Paterna, Roberta,Andre, Vania,Duarte, M. Teresa,Veiros, Luis F.,Candeias, Nuno R.,Gois, Pedro M. P.
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p. 6280 - 6290
(2013/10/21)
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- Development of a series of 3-hydroxyquinolin-2(1H)-ones as selective inhibitors of HIV-1 reverse transcriptase associated RNase H activity
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We report herein the synthesis of a series of 3-hydroxyquinolin-2(1H)-one derivatives. Esters and amide groups were introduced at position 4 of the basis scaffold and some modulations of the benzenic moiety were performed. Most compounds presented selecti
- Suchaud, Virginie,Bailly, Fabrice,Lion, Cedric,Tramontano, Enzo,Esposito, Francesca,Corona, Angela,Christ, Frauke,Debyser, Zeger,Cotelle, Philippe
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supporting information; experimental part
p. 3988 - 3992
(2012/07/03)
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- Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)-one series of potent D-amino acid oxidase (DAAO) inhibitors
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3-Hydroxyquinolin-2(1H)-one (2) was discovered by high throughput screening in a functional assay to be a potent inhibitor of human DAAO, and its binding affinity was confirmed in a Biacore assay. Cocrystallization of 2 with the human DAAO enzyme defined
- Duplantier, Allen J.,Becker, Stacey L.,Bohanon, Michael J.,Borzilleri, Kris A.,Chrunyk, Boris A.,Downs, James T.,Hu, Lain-Yen,El-Kattan, Ayman,James, Larry C.,Liu, Shenping,Lu, Jiemin,Maklad, Noha,Mansour, Mahmoud N.,Mente, Scot,Piotrowski, Mary A.,Sakya, Subas M.,Sheehan, Susan,Steyn, Stefanus J.,Strick, Christine A.,Williams, Victoria A.,Zhang, Lei
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experimental part
p. 3576 - 3585
(2010/03/30)
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- COMPOUND HAVING TGF-BETA INHIBITORY ACTIVITY AND PHARMACEUTICAL COMPOSITION CONTAINING SAME
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The present invention provides compounds of formula (I) or compounds of formula (II) and pharmaceutically acceptable salts or solvates thereof. An objective of the present invention is to provide compounds having TGF2 inhibitory activity.
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Page/Page column 69-70
(2010/11/24)
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- Dioxygenase-catalyzed cis-dihydroxylation of pyridine-ring systems
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Toluene dioxygenase-catalyzed dihydroxylation, in the carbocyclic rings of quinoline, 2-chloroquinoline, 2-methoxyquinoline, and 3-bromoquinoline, was found to yield the corresponding enantiopure cis-5,6- and -7,8-dihydrodiol metabolites using whole cells
- Boyd, Derek R.,Sharma, Narain D.,Modyanova, Ludmila V.,Carroll, Jonathan G.,Malone, John F.,Allen, Christopher C.R.,Hamilton, John T.G.,Gibson, David T.,Parales, Rebecca E.,Dalton, Howard
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p. 589 - 600
(2007/10/03)
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- Glycine receptor antagonist pharmacophore
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Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer''s disease, amyotrophic lateral sclerosis, Huntington''s disease and Down''s syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions and inducing anesthesia are disclosed by administering to an animal in need of such treatment a compound which has high binding to the glycine receptor.
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- 3-Hydroxy-quinolin-2-ones: Inhibitors of [3H]-glycine binding to the site associated with the NMDA receptor
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A series of substituted 3-hydroxy-quinolin-2-one derivatives 6 was synthesized and evaluated as inhibitors of [3H]-glycine and [3H]-AMPA binding to rat cortical membranes. These compounds were generally found to be more potent ligands for the NMDA-associated glycine binding site than the AMPA receptor. Affinity for the glycine site was found to be influenced by both the electronic and steric properties associated with the C-4 substituent and the nature and pattern of substitution of the aromatic ring. The most active compound in this series, 6y, displaces [3H]-glycine with an IC50 of 29 nM.
- Sit, Sing-Yuen,Ehrgott, Frederick J.,Gao, Jinnian,Meanwell, Nicholas A.
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p. 499 - 504
(2007/10/03)
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- Directed ortho-Lithiation of Chloroquinolines. Application to Synthesis of 2,3-Disubstituted Quinolines
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2-, 3- and 4-Chloroguinolines were selectively lithiated at low temperature by lithium diisopropylamide at the more acidic C-3, C-4 and C-3 positions respectively.Reaction of 2-chloro-3-lithioquinoline with electrophiles led to various 2,3-disubstituted quinolines.The versatility of this functionalization methodology is enhanced by the C-2 halogen reactivity towards oxygen or nitrogen nucleophiles.So, a great variety of 2,3-disubstituted quinolines were synthesized, such as 2-chloro, 2-alkoxy, 2-aminoquinolines or 2-quinolones bearing an hydroxy, carbonyl (aldehyde, ketone or carboxylic acid), iodo, trimethylsilyl or boronic acid moiety at the C-3.Some of the resulting 2,3-disubstituted synthons were annelated to tetracyclic polyaromatics, which possess the xanthone or indole structure.This could be achieved via further functionalization of the quinoline ring either by SNAr2 or heteroaromatic cross-coupling reactions, after the first directed-lithiation step.
- Marsais, F.,Godard, A.,Queguiner, G.
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p. 1589 - 1594
(2007/10/02)
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- N-Quaternary Compounds. Part LVI. 3-Hydroxyquinoline-2(1H)-thiones and Their N-Vinylation
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A convenient method for the synthesis of 2,3-dihydroxyquinolines is described.These intermediates are converted to 1,2-dihydrothiazoloquinolinium-4-olates.Ring opening reactions of the latter to the isomeric N- and S-vinylquinolines are affected by
- Johnsen, Bjoern A.,Undheim, Kjell
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p. 109 - 112
(2007/10/02)
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