- Discovery of IACS-9779 and IACS-70465 as Potent Inhibitors Targeting Indoleamine 2,3-Dioxygenase 1 (IDO1) Apoenzyme
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Indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme that mediates the rate-limiting step in the metabolism of l-tryptophan to kynurenine, has been widely explored as a potential immunotherapeutic target in oncology. We developed a class of inhi
- Burke, Jason P.,Cross, Jason B.,Czako, Barbara,Hamilton, Matthew M.,Han, Michelle,Harris, Angela L.,Jiang, Yongying,Jones, Philip,Krapp, Stephan,Lammens, Alfred,Leonard, Paul G.,Lewis, Richard T.,Mandal, Pijus K.,Marszalek, Joseph R.,McAfoos, Timothy J.,Mikule, Keith,Mseeh, Faika,Parker, Connor A.,Petrocchi, Alessia,Pfaffinger, Dana,Reyna, Naphtali J.,Rogers, Norma E.,Soth, Michael J.,Theroff, Jay P.,Tremblay, Martin R.,Trevitt, Graham,Virgin-Downey, Brett,Wilcoxen, Keith,Xu, Alan,Yu, Simon S.
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p. 11302 - 11329
(2021/08/16)
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- tert-Butyl Nitrite as a Twofold Hydrogen Abstractor for Dehydrogenative Coupling of Aldehydes with N-Hydroxyimides
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A synthetically practical transition metal/catalyst/halogen-free dehydrogenative coupling of aldehydes with N-hydroxyimides promoted solely by tert-butyl nitrite under mild conditions was developed. tert-Butyl nitrite generates two radicals (tBuO and NO) and thus works as a twofold hydrogen abstractor. A diverse array of N-hydroxyimide esters were prepared from either aliphatic or aromatic aldehydes. Benzoyl-substituted aldehydes such as 2-oxo-2-phenylacetaldehyde are also suitable.
- Dai, Peng-Fei,Wang, Yi-Ping,Qu, Jian-Ping,Kang, Yan-Biao
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supporting information
p. 9360 - 9364
(2021/12/09)
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- N -Heterocyclic carbene (NHC) catalyzed amidation of aldehydes with amines via the tandem N -hydroxysuccinimide ester formation
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A facile method for the amidation of aldehydes by a cascade approach was developed. This methodology, reported for the first time, uses a N-heterocyclic carbene (NHC) as the catalyst, and N-hydroxysuccinimide (NHS) mediated synthesis of amides utilising TBHP as the oxidant. Various substituted aldehydes reacted smoothly with NHS giving the corresponding active esters in moderate to good yields, which facilely converted into amides in one pot. In addition, the drug moclobemide was synthesized to represent the practical utility of the developed methodology. This journal is
- Singh, Ashmita,Narula
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supporting information
p. 7486 - 7490
(2021/05/13)
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- N-Doped Yellow TiO2 Hollow Sphere-Mediated Visible-Light-Driven Efficient Esterification of Alcohol and N-Hydroxyimides to Active Esters
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Herein we report a simple synthetic protocol for N-doped yellow TiO2 (N-TiO2) hollow spheres as an efficient visible-light-active photocatalyst using aqueous titanium peroxocarbonate complex (TPCC) solution as precursor and NH4OH. In the developed strategy, the ammonium ion of TPCC and NH4OH acts as nitrogen source and structure-directing agent. The synthesized N-TiO2 hollow spheres are capable of promoting the synthesis of active esters of N-hydroxyimide and alcohol through simultaneous selective oxidation of alcohol to aldehyde followed by cross-dehydrogenative coupling (CDC) under ambient conditions upon irradiation of visible light. It is possible to develop a novel and cost-effective one-pot strategy for the synthesis of important esters and amides on gram scale using the developed strategy. The catalytic activity of N-TiO2 hollow spheres is much superior to that of other reported N-TiO2 samples as well as TiO2 with varying morphology.
- Singha, Krishnadipti,Ghosh, Subhash Ch.,Panda, Asit Baran
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p. 3205 - 3212
(2019/09/09)
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- COMPOUNDS USEFUL AS INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND/OR TRYPTOPHAN DIOXYGENASE
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Compounds of formula (VII), which are useful as inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan dioxygenase, are provided. Also provided are pharmaceutical compositions, kits comprising said compounds, and methods and uses pertaining to said compounds.
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Page/Page column 250
(2018/08/12)
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- A photoinduced cross-dehydrogenative-coupling (CDC) reaction between aldehydes and N-hydroxyimides by a TiO2-Co ascorbic acid nanohybrid under visible light irradiation
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In this study, we performed a visible light-mediated aerobic photo-cross dehydrogenative coupling (CDC) reaction between aldehydes and N-hydroxyimides using TiO2-AA-Co as a photocatalyst for the synthesis of active esters. The synergistic and selective effects of the cobalt ascorbic acid complex (Co-AA) and TiO2 nanoparticles on the visible-light photocatalytic activity were explored. The method possesses some advantages such as environmentally friendly conditions, easy work-up procedure, reusability, and scalability.
- Feizpour, Fahimeh,Jafarpour, Maasoumeh,Rezaeifard, Abdolreza
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supporting information
p. 807 - 811
(2018/02/06)
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- Atmospheric oxidative catalyst-free cross-dehydrogenative coupling of aldehydes with N-hydroxyimides
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Cross-dehydrogenative coupling (CDC) reactions of aldehydes with N-hydroxyimidates such as N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI) under catalyst-free conditions is described. Moreover, the desired products can be obtained simply by recrystallization from ethanol. This method is also applicable to the synthesis of amides in excellent yields. A radical mechanism of the type shown in Scheme 4 is proposed based upon the inhibition of the reaction in the presence of TEMPO.
- Xu, Xiaohe,Li, Pingping,Huang, Yingyi,Tong, Chuo,Yan, YiYan,Xie, Yuanyuan
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supporting information
p. 1742 - 1746
(2017/04/13)
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- Iron-Nitrate-Catalyzed Oxidative Esterification of Aldehydes and Alcohols with N-Hydroxyphthalimide: Efficient Synthesis of N-Hydroxyimide Esters
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An Fe(NO3)3·9H2O-catalyzed cross-dehydrogenative coupling reaction between N-hydroxyphthalimide (NHPI) or N-hydroxysuccinimide (NHSI) and aldehydes or alcohols in air is described. This transformation represents an efficient approach to the preparation of N-hydroxyimide ester derivatives in moderate to excellent yields, and has a wide substrate scope.
- Xu, Xiaohe,Sun, Jian,Lin, Yuyan,Cheng, Jingya,Li, Pingping,Jiang, Xiaoying,Bai, Renren,Xie, Yuanyuan
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supporting information
p. 7160 - 7166
(2017/12/28)
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- Metal-free intermolecular C-O cross-coupling reactions: Synthesis of: N -hydroxyimide esters
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Selectfluor-mediated intermolecular C-O cross coupling reaction for the synthesis of N-hydroxyimide esters was developed for the first time. The reaction is applicable to the coupling of readily available aryl and alkyl aldehydes with N-hydroxyphthalimide (NHPI) and N-hydroxysuccinimide (NHSI). The resulting active esters can be directly converted into amides in one pot.
- Lv, Yunhe,Sun, Kai,Pu, Weiya,Mao, Shukuan,Li, Gang,Niu, Jiejie,Chen, Qian,Wang, Tingting
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p. 93486 - 93490
(2016/10/21)
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- Palladium-Catalyzed Carbonylation of (Hetero)Aryl, Alkenyl and Allyl Halides by Means of N-Hydroxysuccinimidyl Formate as CO Surrogate
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An efficient Pd-catalyzed carbonylation protocol is described for the coupling of a large panel of aryl, heteroaryl, benzyl, vinyl and allyl halides 2 with the unusual N-hydroxysuccinimidyl (NHS) formate 1 as a CO surrogate to afford the corresponding valuable NHS esters 3. High conversion to the coupling products was achieved with up to 98% yield by means of Pd(OAc)2/Xantphos catalyst system.
- Barré, Ana?s,T?nta?, Mihaela-Liliana,Alix, Florent,Gembus, Vincent,Papamica?l, Cyril,Levacher, Vincent
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p. 6537 - 6544
(2015/10/05)
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- Cross dehydrogenative coupling (CDC) of aldehydes with N-hydroxyimides by visible light photoredox catalysis
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A photoinduced cross-dehydrogenative-coupling (CDC) reaction between aldehydes and N-hydroxyimides has been developed for the synthesis of ester derivatives. Using 2 mol% [Ru(bpy)3]Cl2 in dry acetonitrile at room temperature with an LED light bulb, we were able to synthesize N-hydroxyesters in good yields. The ester derivatives are very useful synthetic intermediates, which were transformed to amide and oxazole building blocks in excellent yields. This journal is
- Dinda, Milan,Bose, Chandan,Ghosh, Tridev,Maity, Soumitra
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p. 44928 - 44932
(2015/06/02)
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- One-pot synthesis of hydroxamic acids from aldehydes and hydroxylamine
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A one-pot oxidative transformation of aldehydes into hydroxamic acids by the use of an aqueous solution of hydroxylamine is reported. The methodology gives high yields and makes use of cheap, abundant and easily available reagents.
- Dettori, Giovanna,Gaspa, Silvia,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 2709 - 2713
(2014/09/17)
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- A copper-catalysed amidation of aldehydes via N-hydroxysuccinimide ester formation
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A copper-catalysed oxidative amidation of aldehydes via N-hydroxysuccinimide ester formation is reported. The methodology employed to prepare amides directly from aldehydes has a very wide scope, is high yielding, and does not need dry conditions. This cross-coupling reaction appears to be simple and makes use of cheap, abundant and easily available reagents.
- Pilo, Monica,Porcheddu, Andrea,De Luca, Lidia
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p. 8241 - 8246
(2013/12/04)
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- Iodide-catalyzed amide synthesis from alcohols and amines
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An efficient method to prepare amides by a cascade strategy was developed. Using nBu4NI or NaI as the catalyst and tert-butyl hydroperoxide as the oxidant, various alcohols reacted with N-hydroxysuccinimide or N-hydroxyphthalimide affording corresponding active esters in moderate to good yield. The resulting active esters were converted into amides smoothly in one pot. The Royal Society of Chemistry 2013.
- Wang, Gao,Yu, Qing-Ying,Wang, Jian,Wang, Shan,Chen, Shan-Yong,Yu, Xiao-Qi
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p. 21306 - 21310
(2013/11/06)
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- Organocatalytic amidation and esterification of aldehydes with activating reagents by a cross-coupling strategy
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Formation on demand: An organocatalytic cross-coupling reaction of aldehydes with N-hydroxyimides, hexafluoroisopropyl alcohol, and sulfonimides has been developed. The resulting active intermediates can be directly converted into amides or esters in one pot. This simple method makes use of readily available starting materials, and the newly discovered activating reagents should find broad application in the synthesis of amides and esters. Copyright
- Tan, Bin,Toda, Narihiro,Barbas III, Carlos F.
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supporting information
p. 12538 - 12541
(2013/02/22)
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- NON-SIGNAL IMIDAZOLE REAGENTS FOR MASS SPECTROMETRY ANALYSIS OF PHOSPHOMONOESTERS
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Analytical chemical reagents termed non- signal imidazoles and a method for their use that provide a host of advantages for analysis of phosphomonoesters are described. The method and compounds of the invention provide a host of advantages for the analysi
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Page/Page column 12-13
(2008/06/13)
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- Structure-based design and synthesis of the first weak non-phosphate inhibitors for IspF, an enzyme in the non-mevalonate pathway of isoprenoid biosynthesis
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In this paper, we describe the structure-based design, synthesis, and biological evaluation of cytosine derivatives and analogues that inhibit IspF, an enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. This pathway is responsible for the biosynthesis of the C5 precursors to isoprenoids, isopentenyl diphosphate (IPP, 1) and dimethylallyl diphosphate (DMAPP, 2; Scheme 1). The non-mevalonate pathway is the sole source for 1 and 2 in the protozoan Plasmodium parasites. Since mammals exclusively utilize the alternative mevalonate pathway, the enzymes of the non-mevalonate pathway have been identified as attractive new drug targets in the fight against malaria. Based on computer modeling (cf. Figs. 2 and 3), new cytosine derivatives and analogues (Fig. 1) were selected as potential drug-like inhibitors of IspF protein, and synthesized (Schemes 2-5). Determination of the enzyme activity by 13C-NMR spectroscopy in the presence of the new ligands showed inhibitory activities for some of the prepared cytosine and pyridine-2,5-diamine derivatives in the upper micromolar range (IC50 values; Table). The data suggest that it is possible to inhibit IspF protein without binding to the polar diphosphate binding site and the side chain of Asp56′, which interacts with the ribose moiety of the substrate and substrate analogues. Furthermore, a new spacious sub-pocket was discovered which accommodates aromatic spacers between cytosine derivatives or analogues (binding to 'Pocket III') and rings that occupy the flexible hydrophobic region of 'Pocket II'. The proposed binding mode remains to be further validated by X-ray crystallography.
- Baumgartner, Corinne,Eberle, Christian,Diederich, Francois,Lauw, Susan,Rohdich, Felix,Eisenreich, Wolfgang,Bacher, Adelbert
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p. 1043 - 1068
(2008/03/13)
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- N-hydroxysuccinimide-promoted oxidation of primary alcohols and aldehydes to form active esters with hypervalent(III) iodine
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A simple, mild, and efficient method for the conversion of primary alcohols and aldehydes to N-hydroxysuccinimide esters with (diacetoxyiodo)benzene in high yield is developed. N-Hydroxysuccinimide acts not only as an esterification partner but also as an activator of PhI(OAc)2 in this reaction. Copyright
- Wang, Naiwei,Liu, Renhua,Xu, Qing,Liang, Xinmiao
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p. 566 - 567
(2007/10/03)
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- Synthesis of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl carbamate analogs as σ2 receptor ligands
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A series of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs was prepared and their affinities for sigma (σ1 and σ2) receptors were measured in vitro. The results of their structure-activity relationship study ide
- Vangveravong, Suwanna,Xu, Jinbin,Zeng, Chenbo,Mach, Robert H.
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p. 6988 - 6997
(2007/10/03)
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- PROCESS FOR CONVERSION OF PHENOLS TO CARBOXAMIDES VIA THE SUCCINIMIDE ESTERS
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A process for converting an aryl triflate, heteroaryl triflate, aryl halide or heteroaryl halide to an N-hydroxysuccinimido este is disclosed. The process involves reacting the triflate or halide with carbon monoxide and N-hydroxysuccinimide in a solvent in the presence of a palladium catalyst and a base.
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- Preparation of N-hydroxysuccinimido esters via palladium-catalyzed carbonylation of aryl triflates and halides
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N-Hydroxysuccinimido esters of aromatic carboxylic acids (a.k.a. active esters) can be made using a potentially general, one-step procedure via Pd-catalyzed carbonylation of an aryl triflate or aryl iodide with CO and N-hydroxysuccinimide. Excellent yields (up to 94%) were observed when the reaction was done in DMSO at 70°C and 1 atmosphere of CO pressure.
- Lou, Rongliang,VanAlstine, Melissa,Sun, Xufeng,Wentland, Mark P.
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p. 2477 - 2480
(2007/10/03)
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- Benextramine-neuropeptide Y receptor interactions: Contribution of the benzylic moieties to [3H]neuropeptide Y displacement activity
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Analogs of N,N'-bis[6-[(2-methoxybenzyl)amino]hex-1-yl]cystamine (benextramine, BXT, 2) were synthesized using solution-phase peptide synthesis methodology and analyzed for activity in displacing specifically bound 1 nM N-[propionyl-3H]neuropeptide Y([3H]NPY) from benextramine- sensitive neuropeptide Y (NPY) binding sites in rat brain. Our new synthetic approach to these analogs began with the acylation of cystamine with the N- hydroxysuccinimide ester of tert-butyloxycarbonyl (t-Boc) protected 6- aminohexanoic acid, followed by deprotection of the t-Boc groups with 4 N HCl in dioxane. Acylation of this symmetric diamine with N-hydroxysuccinimide esters of appropriately substituted benzoic acids, followed by reduction of the resultant tetraamides with diborane in refluxing THF, afforded the target compounds. The BXT analog lacking the benzylic group (i.e., compound 11) had no [3H]NPY displacement activity at concentrations up to 1.4 x 10-3 M. The 9-fold range in activities observed for the ortho, meta, and para regioisomers of the methoxy, chloro, and hydroxy benextramine analogs at benextramine-sensitive NPY rat brain binding sites does not differ from the range of potencies observed at α-adrenoceptors. However, the order of potencies at [3H]NPY sites differs from the order of potencies at α- adrenoceptors, with the m-methoxyphenyl (9a), m-hydroxyphenyl (10b), and 2- naphthyl (9f) analogs being the most active at [3H]NPY binding sites. The present results demonstrate the importance of the benzylic moiety for BXT's NPY antagonist activity, and suggest that the BXT binding site on the NPY receptor is significantly distinct from that on the α-adrenoceptor.
- Doughty,Chaurasia,Li
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p. 272 - 279
(2007/10/02)
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