- Discovery and structure-activity relationship studies of 1-aryl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as potent dual inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) and trytophan 2,3-dioxygenase (TDO)
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Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO), which mediate kynurenine pathway of tryptophan degradation, have emerged as potential new targets in immunotherapy for treatment of cancer because of their critical role in immunosuppression in the tumor microenvironment. In this investigation, we report the structural optimization and structure-activity relationship studies of 1-phenyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as a new class of IDO1/TDO dual inhibitors. Among all the obtained dual inhibitors, 1-(3-chloro-4-fluorophenyl)-6-fluoro-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione (38) displayed the most potent IDO1 and TDO inhibitory activities with IC50 (half-maximal inhibitory concentration) values of 5 nM for IDO1 and 4 nM for TDO. It turned out that compound 38 was not a PAINS compound. Compound 38 could efficiently inhibit the biofunction of IDO1 and TDO in intact cells. In LL2 (Lewis lung cancer) and Hepa1-6 (hepatic carcinoma) allograft mouse models, this compound also showed considerable in vivo anti-tumor activity and no obvious toxicity was observed. Therefore, 38 could be a good lead compound for cancer immunotherapy and deserving further investigation.
- Pan, Shulei,Zhou, Yangli,Wang, Qiusheng,Wang, Yanlin,Tian, Chenyu,Wang, Tianqi,Huang, Luyi,Nan, Jinshan,Li, Linli,Yang, Shengyong
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- Copper-mediated tandem ring-opening/cyclization reactions of cyclopropanols with aryldiazonium salts: Synthesis of: N -arylpyrazoles
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A general method for the synthesis of structurally diverse N-arylpyrazoles from readily available cyclopropanols and aryldiazonium salts is disclosed. The reaction was conducted at room temperature within minutes with a broad substrate scope and excellent regioselectivity.
- Liu, Jidan,Xu, Erjie,Jiang, Jinyuan,Huang, Zeng,Zheng, Liyao,Liu, Zhao-Qing
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supporting information
p. 2202 - 2205
(2020/02/26)
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- Copper(I)-promoted trifluoromethylthiolation of arenediazonium salts with AgSCF3
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An efficient method for trifluoromethylthiolation of arenediazonium salts has been developed in mild conditions with a stable and convenient AgSCF3. It provides a straightforward and convenient way for the synthesis of trifluoromethylthiolated compound from diazonium salts in moderate to good yields.
- Zheng, Changge,Liu, Yang,Hong, Jianquan,Huang, Shuai,Zhang, Wei,Yang, Yupeng,Fang, Ge
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supporting information
p. 1404 - 1407
(2019/05/01)
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- Palladium catalyzed stereocontrolled synthesis of C-aryl glycosides using glycals and arenediazonium salts at room temperature
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A stereocontrolled synthesis of aryl-C-glycosides was achieved using glycals and aryldiazonium salts in the presence of palladium acetate. A wide range of glycals including d-glucal, d-galactal, l-rhamnal, d-xylal and d-ribal underwent C-arylation at the anomeric carbon in the presence of different aryldiazonium tetrafluoroborates and gave synthetically useful 2,3-deoxy-3-keto-α-aryl-C-glycosides in good to excellent yields. Broad substrate scope, simple operation and room temperature reactions make this protocol very attractive in organic synthesis.
- Singh, Adesh Kumar,Kandasamy, Jeyakumar
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supporting information
p. 5107 - 5112
(2018/07/29)
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- Visible-Light-Mediated Hydroxycarbonylation of Diazonium Salts
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A visible light-promoted catalytic photoredox hydroxycarbonylation was achieved on aryl diazonium salts whether preformed or generated in situ from the corresponding anilines. This strategy allows a straightforward access to a variety of carboxylic acids under mild conditions. (Figure presented.).
- Gosset, Cyrille,Pellegrini, Sylvain,Jooris, Romain,Bousquet, Till,Pelinski, Lydie
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supporting information
p. 3401 - 3405
(2018/08/06)
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- Tandem and chemoselective synthesis of benzil derivatives from styrene and arene diazonium salts
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A facile and practically applied protocol for synthesis of benzil derivatives using styrene and arene diazonium salts is reported. Pd(OAc)2/SeO2 catalytic system was found to be efficient for chemoselective synthesis of benzil. Selenium dioxide works well as an oxidant under milder reaction conditions. Moderate to very good yields of the desired products were obtained.
- Jadhav, Vilas G.,Sarode, Sachin A.,Nagarkar, Jayashree M.
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supporting information
p. 1834 - 1838
(2017/04/21)
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- Synthesis of difluoromethyl thioethers from difluoromethyl trimethylsilane and organothiocyanates generated in situ
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A copper-CF2H complex generated in situ from copper thiocyanate and TMS-CF2H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one-pot protocols, allowing late-stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts. This strategy enables the introduction of difluoromethylthio groups - a largely unexplored substituent with highly promising properties - into drug-like molecules. A copper-CF2H complex generated in situ from copper thiocyanate and TMS-CF2H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one-pot protocols, allowing late-stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts.
- Bayarmagnai, Bilguun,Matheis, Christian,Jouvin, Kvin,Goossen, Lukas J.
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supporting information
p. 5753 - 5756
(2015/06/10)
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- Aryldiazonium Tetrafluoroborate Salts as Green and Efficient Coupling Partners for the Suzuki-Miyaura Reaction: From Optimisation to Mole Scale
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The use of aryldiazonium tetrafluoroborate salts as coupling partners in the Suzuki-Miyaura reaction was investigated from a process chemistry perspective including safety evaluation, solvent and catalyst screening and multivariate factor optimisation. Optimised conditions were applied to a range of substrates to evaluate the scope and limitations of the reaction, and one example was carried out on mole scale to demonstrate the practicality and scalability of the process.
- Colleville, Aymeric P.,Horan, Richard A. J.,Tomkinson, Nicholas C. O.
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supporting information
p. 1128 - 1136
(2015/04/22)
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- An easy route to (hetero)arylboronic acids
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An unprecedented spontaneous reactivity between diazonium salts and diboronic acid has been unveiled, leading to a versatile arylboronic acid synthesis directly from (hetero)arylamines. This fast reaction (35 min overall) tolerates a wide range of functional groups and is carried out under very mild conditions. The radical nature of the reaction mechanism has been investigated.
- Erb, William,Hellal, Akila,Albini, Mathieu,Rouden, Jacques,Blanchet, Jerome
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supporting information
p. 6608 - 6612
(2014/06/09)
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- The photoredox-catalyzed meerwein addition reaction: Intermolecular amino-arylation of alkenes
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A variety of amides are efficiently accessible under mild conditions by intermolecular amino-arylation using a photo Meerwein addition with visible light. The reaction has a broad substrate scope, tolerates a large range of functional groups, and was applied to the synthesis of a 3-aryl-3,4- dihydroisoquinoline. From elimination to addition: A variety of amides are efficiently accessible under mild conditions by intermolecular amino-arylation using a photo Meerwein addition with visible light. The reaction has a broad substrate scope, tolerates a large range of functional groups, and was applied to the synthesis of 3-aryl-3,4-dihydroisoquinoline. Copyright
- Prasad Hari, Durga,Hering, Thea,K?nig, Burkhard
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supporting information
p. 725 - 728
(2014/01/23)
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- A transition-metal-free synthesis of arylcarboxyamides from aryl diazonium salts and isocyanides
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A transition-metal-free carboxyamidation process, using aryl diazonium tetrafluoroborates and isocyanides under mild conditions, has been developed. This novel conversion was initiated by a base and solvent induced aryl radical, followed by radical addition to isocyanide and single electron transfer (SET) oxidation, affording the corresponding arylcarboxyamide upon hydration of the nitrilium intermediate.
- Xia, Zhonghua,Zhu, Qiang
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supporting information
p. 4110 - 4113
(2013/09/12)
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- Halo- and azidodediazoniation of arenediazonium tetrafluoroborates with trimethylsilyl halides and trimethylsilyl azide and Sandmeyer-type bromodediazoniation with Cu(I)Br in [BMIM][PF6] ionic liquid
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(Chemical Equation Presented) Reaction of [ArN2][BF4] salts immobilized in [BMIM][PF6] ionic liquid (IL) with TMSX (X = I, Br) and TMSN3 represents an efficient method for the preparation of iodo-, bromo-, and azido-derivatives via dediazoniation. The reactions can also be effected starting with ArNH2 by in situ diazotization with [NO][BF4] followed by reaction with TMSX or TMSN3. Depending on the substituents on the benzenediazonium cation, competing fluorodediazoniation (ArF formation) and hydrodediazoniation (ArH formation) were observed. Dediazoniation with TMSN3 and with TMSI generally gave the highest chemoselectivity toward ArN3 and ArI formation. The IL was recycled and reused up to 5 times with no appreciable decrease in the conversions. Multinuclear NMR monitoring of the interaction of [ArN 2][BF4]/TMSX, [BMIM][PF6]/TMSX, and [BMIM][PF6]/TMSX/[ArN2][BF4] indicated that TMSF is formed primarily via [ArN2][BF4]/ TMSX, generating [ArN2][X] in situ, which gives ArX on dediazoniation. Competing formation of ArF in Sandmeyer-type bromodediazoniation of [ArN 2][BF4] with Cu(I)Br immobilized in the IL points to significant involvement of heterolytic dediazoniation.
- Hubbard, Abigail,Okazaki, Takao,Laali, Kenneth K.
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p. 316 - 319
(2008/09/17)
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- Sandmeyer reactions. Part 7.1 An investigation into the reduction steps of Sandmeyer hydroxylation and chlorination reactions
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For Sandmeyer hydroxylation and chlorination in aqueous solution, the reduction steps have been investigated by means of correlation analyses of the effects of diazonium ion substitution on the rates of reduction. For simple hydroxylation, a change of behaviour between diazonium ions substituted by electron donor groups and those substituted by electron acceptor groups is interpreted as a change within an inner-sphere process from rate-determining electron transfer to rate-determining association of the reactants. By contrast, for citrate-promoted hydroxylation, a similar change in behaviour may be interpreted as a change between inner- and outer-sphere electron transfers. For chlorination, there is no mechanistic variation within the range of substituents examined but the pattern of behaviour is consistent with an inner-sphere mechanism. The various patterns of behaviour are rationalised in terms of the effects of diazonium ion substitution and catalyst ligation on the reduction potentials and self-exchange rates of the various reacting redox couples. Comparative correlation analyses of reductions and other electrophilic reactions of diazonium ions are used to support the arguments advanced in respect of Sandmeyer reduction steps. It is suggested that the Cu1 reductants react via a nucleophilic bridging ligand at the diazonium Nβ to give transient Z-adducts which are the precursor complexes and that activation for electron transfer involves rotation about the N-N bond.
- Hanson, Peter,Jones, Jason R.,Taylor, Alec B.,Walton, Paul H.,Timms, Allan W.
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p. 1135 - 1150
(2007/10/03)
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- Rates and mechanisms of the thermal solvolytic decomposition of arenediazonium ions
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Arenediazonium tetrafluoroborates have been prepared and the kinetics of solvolysis have been investigated in water, trifluoroethanol, water-trifluoroethanol mixtures, hexafluoropropan-2-ol, trifluoroacetic acid, and ethanol by a UV method. A heterolytic mechanism involving short-lived aryl cations leads to products derived from nucleophilic capture of the aryl cations by solvent or a solute. Ionic solutes in aqueous trifluoroethanol and trifluoromethoxybenzene in trifluoroethanol have no kinetic effect and neither does replacement of the tetrafluoroborate counter-ion by chloride in trifluoroethanol. Rate constants for any one compound are not very solvent dependent, the reactions generally being characterised by high enthalpies of activation and appreciably positive entropies of activation. Compounds with 4-Cl, 4-F, 4-NO2, and 4-MeO substituents proved too unreactive for kinetic studies, but for different reasons. In ethanol, a radical reaction with characteristically different activation parameters competes with the heterolytic path and leads to hydrodediazoniation (reduction) by hydrogen atom abstraction from the CH2 group of ethanol.
- Canning, Peter S. J.,McCrudden, Katharine,Maskill, Howard,Sexton, Brian
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p. 2735 - 2740
(2007/10/03)
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- STUDIES OF CROWN ETHER COMPLEXES; ARYLDIAZONIUM ION COMPLEXES
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DNMR studies show that for complexation of aryldiazonium salts 21-crown-7 is the preferred host.
- Krane, Jostein,Skjetne, Tore
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p. 1775 - 1778
(2007/10/02)
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