- One pot synthesis of α-N-heteroaryl ketone derivatives from aryl ketones using aqueous NaICl2
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A simple and efficient method for the synthesis of α-heteroaryl ketones from aryl ketones and amine using aqueous sodium dichloroiodate is established. This method is mild, operationally simple, has a short reaction time, and easy workup procedure to afford the corresponding α-N-heteroaryl ketone derivatives in moderate to good yield.
- Ghodse, Shrikant M.,Hatvate, Navnath T.,Telvekar, Vikas N.
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supporting information
(2021/12/08)
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- Structure–activity relationships (SARs) of α- ketothioamides as inhibitors of phosphoglycerate dehydrogenase (PHGDH)
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For many years now, targeting deregulation within cancer cells’ metabolism has appeared as a promising strategy for the development of more specific and efficient cancer treatments. Recently, numerous reports highlighted the crucial role of the serine synthetic pathway, and particularly of the phosphoglycerate dehydrogenase (PHGDH), the first enzyme of the pathway, to sustain cancer progression. Yet, because of very weak potencies usually in cell-based settings, the inhibitors reported so far failed to lay ground on the potential of this approach. In this paper, we report a structure–activity relationship study of a series of α-ketothioamides that we have recently identified. Interestingly, this study led to a deeper understanding of the structure–activity relationship (SAR) in this series and to the identification of new PHGDH inhibitors. The activity of the more potent compounds was confirmed by cellular thermal shift assays and in cell-based experiments. We hope that this research will eventually provide a new entry point, based on this promising chemical scaffold, for the development of therapeutic agents targeting PHGDH.
- Spillier, Quentin,Ravez, Séverine,Unterlass, Judith,Corbet, Cyril,Degavre, Charline,Feron, Olivier,Frédérick, Rapha?l
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- Solvent-Free Synthesis of α-Amino Ketones from α-Hydroxyl Ketones via A Novel Tandem Reaction Sequence Based on Heyns Rearrangement
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Heyns rearrangement have been famous for carbohydrate chemists for several decades. However, this reaction was underrated as a useful method for synthetic chemists due to preparative shortcomings. Herein we developed an efficient method for the synthesis of pharmaceutically important α-amino ketones from readily available α-hydroxy ketones and secondary amines through a tandem reaction sequence based on Heyns rearrangement. The reaction smoothly proceeded by using catalytic PTSA as catalyst without solvent. Primary and secondary α-hydroxy ketones were readily used and regioselectively afforded the correspondingly α-amino ketones with moderate yield.
- Li, Ling-Yu,Zeng, Qing-Le,Li, Guang-Xun,Tang, Zhuo
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supporting information
p. 694 - 699
(2019/03/26)
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- Enabling nucleophilic substitution reactions of activated alkyl fluorides through hydrogen bonding
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It was discovered that the presence of water as a cosolvent enables the reaction of activated alkyl fluorides for bimolecular nucleophilic substitution reactions. DFT calculations show that activation proceeds through stabilization of the transition structure by a stronger F···H 2O interaction and diminishing C-F bond elongation, and not simple transition state electrostatic stabilization. Overall, the findings put forward a distinct strategy for C-F bond activation through H-bonding.
- Champagne, Pier Alexandre,Pomarole, Julien,Therien, Marie-Eve,Benhassine, Yasmine,Beaulieu, Samuel,Legault, Claude Y.,Paquin, Jean-Francois
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p. 2210 - 2213
(2013/06/26)
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- Simplified heterocyclic analogues of fluoxetine inhibit inducible nitric oxide production in lipopolysaccharide-induced BV2 cells
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A series of fluoxetine, where the N-methylamino group was replaced and then simplified, were synthesized and their inhibitory effect was tested for nitric oxide (NO) production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-induced BV2 cells. Although the synthesized compounds generally revealed weaker activity or greater cytotoxicity than fluoxetine, compound 10a, in which the N-methylamino group in fluoxetine was replaced by morpholine, and the trifluoromethylphenyl ring was substituted with simple oxo group, suppressed NO production dose-dependently at 10, 20 and 40 μM concentrations with less cytotoxicity than fluoxetine, and inhibited iNOS mRNA and protein expression at the same concentrations in LPS-induced BV2 cells. The results suggested that the trifluoromethylphenyl ring moiety in fluoxetine is not necessary for the suppression of NO production and that 10a has the potential as a potent inhibitor of NO production.
- Park, Ju-Young,Kim, Seung-Woo,Lee, Ja-Kyeong,Im, Weon Bin,Jin, Byung Kwan,Yoon, Sung-Hwa
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experimental part
p. 538 - 544
(2012/02/15)
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- Biomimetic transfer hydrogenation of 2-alkoxy- and 2-aryloxyketones with iron-porphyrin catalysts
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In situ generated iron porphyrins are applied as homogeneous catalysts in the transfer hydrogenation of α-substituted ketones. Using 2-propanol as hydrogen donor various protected 1,2-hydroxyketones are reduced to the corresponding mono-substituted 1,2-di
- Enthaler, Stephan,Spilker, Bj?rn,Erre, Giulia,Junge, Kathrin,Tse, Man Kin,Beller, Matthias
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p. 3867 - 3876
(2008/09/20)
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- Novel N,S-phenacyl protecting group and its application for peptide synthesis
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The phenacyl group can be introduced onto amino and thio groups by N,S-alkylation reactions. Conversely, these groups are removed rapidly by employing magnesium in acetic acid. This protecting group was successfully applied to a short peptide synthesis of Boc-L-Cys-Gly-OMe. Georg Thieme Verlag Stuttgart.
- Tang, Guo,Ji, Tao,Hu, An-Fu,Zhao, Yu-Fen
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experimental part
p. 1907 - 1909
(2009/04/11)
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- Synthesis and Biological activity of kappa opioid receptor agonists. Part 2: Preparation of 3-aryl-2-pyridone analogues generated by solution- and solid-phase parallel synthesis methods
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New analogues of the previously described 3-aryl pyridone KOR agonists have been synthesised by parallel synthetic methods, both in solution- and with solid-phase chemistry, making use of the well known and versatile Mitsunobu, Suzuki and Buchwald reactions. Opioid receptor binding data for the compounds produced is reported.
- Semple, Graeme,Andersson, Britt-Marie,Chhajlani, Vijay,Georgsson, Jennie,Johansson, Magnus J.,Rosenquist, Asa,Swanson, Lars
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p. 1141 - 1145
(2007/10/03)
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- Indium tribromide: A highly effective catalyst for the addition of trimethylsilyl cyanide to α-hetero-substituted ketones
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The catalytic addition of trimethylsilyl cyanide (TMSCN) to a large variety of hetero-substituted ketones promoted by anhydrous InBr3 has been studied. The low catalytic loading (0.1-1 mol%) and the mild experimental conditions required represe
- Bandini, Marco,Cozzi, Pier Giorgio,Melchiorre, Paolo,Umani-Ronchi, Achille
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p. 3041 - 3043
(2007/10/03)
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- Highly chemoselective α-diazo carbonyl insertion reactions into N-H and S-H bonds catalysed by [RuCl(η5-C5H5)(PPh3)2]
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Complex [RuCl(η5-C5H5)(PPh3)2], in chloroform at 60 deg C, catalyses the chemoselective insertion of α-diazo carbonyl compounds into N-H and S-H bonds to afford α-keto-amines and α-keto-thioethers.
- Del Zotto, Alessandro,Baratta, Walter,Rigo, Pierluigi
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p. 3079 - 3082
(2007/10/03)
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- Epoxyethane-/ethynesulfonamides with antifilarial activities degradation kinetics and inhibitory effect on filarial malate dehydrogenase and lactate dehydrogenase
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Some eppxyethane-/ethynesulfonamides had shown strong filaricidal activity with inconstant reproducibility as a result of a lack of stability in aqueous solution. The degradation in hydroxylic and aprotic solutions of two epoxyethanesulfonamides and one ethynesulfonamide was investigated using TLC, HPLC, GC and mass spectrometry. For both epoxydes, the degradation rate followed first-order kinetics and was more rapid in hydroxylic than in aprotic solutions. The degradation increased with the temperature whereas it was not modified with and without light exposure. Four kinds of degradation products were found: the first one involved the oxidation of the epoxyde bond, the second the breaking of the N-S bond, the third a desulfonation product and the fourth was not identified. In contrast, the stability of ethynesulfonamide was better than those of epoxyethanesulfonamide. These results suggest that epoxyethanesulfonamides should be kept at + 4 °C before being injected to animals during the study of biological activity. Since epoxyde compounds are known to have inhibitory effects on parasite energy metabolism enzymes, the compounds were evaluated on two major filarial enzymes: lactate dehydrogenase (LDH) and cytoplasmic malate dehydrogenase (MDH). Both epoxyethanesulfonamides showed only a slight inhibitory effect on filarial LDH and MDH confirming the evidence that the main mode of action of these compounds remains to discover. Moreover, ethynesulfonamide and the degradation products of both epoxyethanesulfonamides had no effect on LDH and MDH.
- Radembino, Nathalie,Loiseau, Philippe M.,Dessalles, Marie-Christine,Marchat, Laurence,Bories, Christian,Gayral, Philippe,Mahuzier, Georges
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p. 294 - 299
(2007/10/03)
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- Synthesis of chiral alcohols by asymmetric reductions of various ketones including α-aminophenones
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LiAlH4 previously treated with 2.5 equiv. of (S)-(+) or (R)-(-)-2-(2-isoindolinyl)butan-1-ol 1 reduced the six α-aminophenones 4-9 into the corresponding optically active β-aminoalcohols 10-15 whose ee's were in the range of 40-97% after chroma
- Brown, Eric,Leze, Antoine,Touet, Joel
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p. 2029 - 2040
(2007/10/03)
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- α-amino ketone synthesis from aldehydes and N-(α-dialkylaminoalkyl)benzotriazoles
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Thiazolium salt-catalyzed reactions of aldehydes with morpholino-(alkylbenzotriazoles) allow the synthesis of a variety of α-amino ketones. The relationship between reaction conditions and selectivity is discussed.
- Katritzky, Alan R.,Cheng, Dai,Musgrave, Richard P.
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p. 273 - 280
(2007/10/02)
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- The SN2 Reactivity of 3,3-Disubstituted 1,2-Dioxetanes with Morpholine
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The reaction of morpholine with the 3-aryl-3-methyldioxetanes 1a-c (Y = 4-OMe, H, 4-NO2), the 3-(methoxymethyl)-3-phenyldioxetane (1d), and the 3-(halomethyl) 3-phenyldioxetanes 1e,f (X = Cl, Br) was investigated to determine the SN2 reactivity of these dioxetanes and the product distribution of the hydroxylamine ether 2 adducts and the dioxetane fragmentation products 3.It was shown that the overall reactivity and the product distribution are strongly dependent on the substituents of the dioxetanes 1.Thus, the reactivity of the dioxetanes 1 toward morpholine was demonstrated to correlate with the electron-accepting propensity of the substituents in the 3-position, while the product distribution depends on the electronic features of the primary dipolar adduct, which results from nucleophilic attack at the dioxetane peroxide bond.Electron-donating substituents (Y = 4-OMe) favor proton transfer from the hydroxylammonium site to the alkoxide ion due to the enhanced basicity of the latter, and, therefore, the formation of the hydroxylamine ether 2 is promoted.Additionally, electron-accepting substituents (Y = NO2) facilitate the Grob fragmentation of the primary dipolar adduct to the dioxetane cleavage products 3.The unexpected formation of the hydroperoxide 4f in the reaction of the dioxetane 1f with morpholine was shown to result from acid-catalyzed ring opening of the dioxetane by morpholinium bromide and subsequent morpholine trapping of the resulting stabilized, bromine-bridged benzylic cation.
- Adam, Waldemar,Stoessel, Roland,Treiber, Alexander
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p. 2879 - 2884
(2007/10/02)
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- Boranes in Synthesis. 2. Asymmetric Synthesis of β-Amino Alcohols. A Facile Conversion of 2-Amino Acetophenones to the Corresponding β-Amino Alcohols in High Enantiomeric Purity
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The asymmetric reduction of 2-amino acetophenones with Ipc2BH or Ipc2BCl at -78 deg C, yields the corresponding β-amino alcohols in good to excellent yields.Although only modest (12-45percent ee) enantiomeric excesses were obtained with Ipc2BH, 75-99perce
- Beardsley, David A.,Fisher, Gary B.,Goralski, Christian T.,Nicholson, Lawrence W.,Singaram, Bakthan
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p. 1511 - 1514
(2007/10/02)
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- Isoindolone derivatives, their preparation and the pharmaceutical compositions containing them
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This invention relates to isoindolone derivatives of general formula (I) in which the radicals R are hydrogen atoms or together form a bond, the symbols R'' are phenyl radicals which can be substituted by a halogen atom or a methyl radical in position 2 or 3, X is an oxygen or sulphur atom or a radical N--R 3, R 3 being H, optionally substituted alkyl or dialkylamino, R 1 is optionally substituted phenyl or cyclohexadienyl, naphthyl or a heterocycle and R 2 is H, halogen, OH, alkyl, amionoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxy, alkylthio, acyloxy, carboxyl, optionally substituted alkoxycarbonyl, benzyloxycarbonyl, amino or acylamino, in their (3aR,7aR) forms or in the (3aRS,7aRS) form or their mixtures, and if appropriate their salts where such exist, and their preparation.The new derivatives according to the invention are particularly valuable as antagonists of substance P. STR1
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- A New Thiazolium Salt-Catalyzed Synthesis of α-Aminoketones from Aldehydes and Iminium Salts
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A new reaction, closely related to both the classical Mannich reaction and the benzoin condensation, affords α-aminoketones from aldehydes and in situ prepared N-methylenemorpholinium or N-methylenepiperidinium salts.
- Castells, J.,Lopez-Calahorra, F.,Bassedas, M.,Urrios, P.
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p. 314 - 315
(2007/10/02)
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- New antifilarial agents. 1. Epoxy sulfonamides and ethynesulfonamides
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Two series of 2-substituted 1,2-epoxyethanesulfonamides 2 and ethynesulfonamides 5 were synthesized and evaluated for their antifilarial activity. The trans epoxides 2T were stereospecifically prepared by a Darzens reaction between aldehydes and halomethanesulfonamides. The cis isomers 2c were obtained from ethynesulfonamides 5 by semihydrogenation followed by KOCl epoxidation. 2-Substituted ethynesulfonamides 5 were synthesized from appropriate trans-ethenesulfonamides by a bromination/dehydrobromination sequence. These products, as well as several synthetic intermediates, were evaluated for antifilarial activity against Molinemia dessetae either in vivo in its natural host, the rodent Proechimys oris, or in vitro by a new test using cultures of the infective larvae. Most of the epoxides 2T and acetylenic derivatives 5 bearing a 2-aryl substituent were active in vitro. Among these compounds, four epoxides 2T and one acetylenic derivative 5 showed marked macrofilaricidal activity in vivo without any microfilaricidal activity. The differences between the in vivo and in vitro results may be due, in part, to the low chemical stability of the epoxy sulfonamides 2T. Despite this limitation, the activities observed in this reliable animal model suggest further development and testing of both series 2T and 5 as macrofilaricides.
- Brienne,Varech,Leclercq,Jacques,Radembino,Dessalles,Mahuzier,Gueyouche,Bories,Loiseau,Gayral
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p. 2232 - 2239
(2007/10/02)
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- The Reactions of α-Arylsulfonoxy Ketones with Nucleophiles
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α-(p-Nitrophenyl)sulfonoxy ketones can be converted to α-hydroxy ketals and α-hydroxy ketones by reaction with potassium carbonate and basic or acidic workup, respectively.They also react with amines to give α-amino ketones in high yields.Nonnucleophilic amines give an intramolecular aromatic substitution in the derived enolate.Factors which dictate the reaction patterns in these compounds are discussed.
- Hoffman, Robert V.,Jankowski, Bryan C.,Carr, C. Sean,Duesler, Eileen N.
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p. 130 - 135
(2007/10/02)
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- NOVEL APPLICATIONS OF α-AMINOSUBSTITUTED DIPHENYLPHOSPHINE OXIDES. THE CONVERSION OF ALDEHYDES INTO α-AMINOMETHYLKETONES.
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Aromatic and aliphatic aldehydes (R3CHO) can be converted into α-aminomethylketones (R3COCH2NR1R2) via reaction with (α-aminomethyl)diphenylphosphine oxides.
- Broekhof, Nico L.J.M.,Gen, Arne van der
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p. 2799 - 2802
(2007/10/02)
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