- Axially Chiral Aryl-Alkene-Indole Framework: A Nascent Member of the Atropisomeric Family and Its Catalytic Asymmetric Construction
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A new class of axially chiral aryl-alkene-indole frameworks have been designed, and the first catalytic asymmetric construction of such scaffolds has been established by the strategy of organocatalytic (Z/E)-selective and enantioselective (4+3) cyclization of 3-alkynyl-2-indolylmethanols with 2-naphthols or phenols (all >95 : 5 E/Z, up to 98% yield, 97% ee). This reaction also represents the first catalytic asymmetric construction of axially chiral alkene-heteroaryl scaffolds, which will add a new member to the atropisomeric family. This approach has not only confronted the great challenges in constructing axially chiral alkene-heteroaryl scaffolds but also provided a powerful strategy for the enantioselective construction of axially chiral aryl-alkene-indole frameworks.
- Deng, Shuang,Jiao, Yinchun,Li, Tian-Zhen,Liu, Si-Jia,Shi, Feng,Wang, Cong-Shuai,Zhang, Yu-Chen
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Read Online
- Synthesis and evaluation of heterocycle structures as potential inhibitors of Mycobacterium tuberculosis UGM
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In this study, we screen three heterocyclic structures as potential inhibitors of UDP-galactopyranose mutase (UGM), an enzyme involved in the biosynthesis of the cell wall of Mycobacterium tuberculosis. In order to understand the binding mode, docking simulations are performed on the best inhibitors. Their activity on Mycobacterium tuberculosis is also evaluated. This study made it possible to highlight an “oxazepino-indole” structure as a new inhibitor of UGM and of M. tuberculosis growth in vitro.
- Fu, Jian,Hammoud, Sokaina,Kremer, Laurent,Maaliki, Carine,Raynaud, Clément,Thibonnet, Jér?me,Thiery, Emilie,Viljoen, Albertus,Villaume, Sydney,Vincent, Stéphane P.
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Read Online
- Synthesis and Reactivity of Oxazinoindolones via Regioselective 6-exo-dig Iodolactonization
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An efficient protocol for the facile construction of 3,4-dihydro-10-iodo-3-iodomethylene-[1,4]-oxazino[4,3-a]indol-1-ones has been developed by using a regio- and stereoselective iodolactonization reaction. Subsequent palladium cross-coupling reactions of 3,4-dihydro-10-iodo-3-iodomethylene-[1,4]-oxazino[4,3-a]indol-1-ones readily afforded functionalized oxazinoindolones.
- Hammoud, Sokaina,Anselmi, Elsa,Cherry, Khalil,Kizirian, Jean-Claude,Thibonnet, Jér?me
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Read Online
- Neuroprotective Effect of IND1316, an Indole-Based AMPK Activator, in Animal Models of Huntington Disease
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Aggregation of mutant huntingtin, because of an expanded polyglutamine track, underlies the cause of neurodegeneration in Huntington disease (HD). However, it remains unclear how some alterations at the cellular level lead to specific structural changes in HD brains. In this context, the neuroprotective effect of the activation of AMP-activated protein kinase (AMPK) appears to be a determinant factor in several neurodegenerative diseases, including HD. In the present work, we describe a series of indole-derived compounds able to activate AMPK at the cellular level. By using animal models of HD (both worms and mice), we demonstrate the in vivo efficacy of one of these compounds (IND1316), confirming that it can reduce the neuropathological symptoms of this disease. Taken together, in vivo results and in silico studies of druggability, allow us to suggest that IND1316 could be considered as a promising new lead compound for the treatment of HD and other central nervous system diseases in which the activation of AMPK results in neuroprotection.
- Vela, Marta,García-Gimeno, María Adelaida,Sanchis, Ana,Bono-Yagüe, José,Cumella, José,Lagartera, Laura,Pérez, Concepción,Priego, Eva-María,Campos, Angela,Sanz, Pascual,Vázquez-Manrique, Rafael P.,Castro, Ana
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p. 275 - 287
(2022/01/15)
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- Aryl halide and synthesis method and application thereof
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The invention discloses a synthesis method of aryl halides (including aryl bromide shown as a formula (2) and aryl iodide shown as a formula (3)). All the systems are carried out in an air atmosphere,visible light is utilized to excite a substrate or a photosensitizer to catalyze the reaction; and in a reaction solvent, when aromatic hydrocarbon shown in the formula (1) and sodium bromide serve as raw materials, aryl bromide shown in the formula (2) is obtained through a reaction under the auxiliary action of an additive (protonic acid); or when aromatic hydrocarbon shown in the formula (1) and sodium iodide are used as raw materials, under the auxiliary action of an additive (protonic acid), aryl iodide shown in the formula (3) is obtained through reaction. The synthesis method has the advantages of cheap and accessible raw materials, simple reaction operation and mild reaction conditions. The method is compatible with the arylamine which is liable to be oxidized. The invention provides a new method for the synthesis of aryl halides, realizes the amplification of basic chemicals aryl halides including aryl bromide shown in the formula (2) and aryl iodide shown in the formula (3),and has wide application prospect and practical value.
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Paragraph 0133-0135
(2020/06/02)
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- Visible-light-promoted oxidative halogenation of (hetero)arenes
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Organic halides are critical building blocks that participate in various cross-coupling reactions. Furthermore, they widely exist as natural products and artificial molecules in drugs with important physiological activities. Although halogenation has been well studied, to the best of our knowledge, studies focussing on sensitive systems (e.g.aryl amines) have not been reported. Herein, we describe a compatible oxidative halogenation of (hetero)arenes with air as the oxidant and halide ions as halide sources under ambient conditions (visible light, air, aqueous system, room temperature, and normal pressure). Moreover, this protocol is practically feasible for gram-scale synthesis, showing potential for industrial application.
- Jiang, Xuefeng,Li, Yiming,Lu, Lingling
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supporting information
p. 5989 - 5994
(2020/10/18)
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- Disulfide-Catalyzed Iodination of Electron-Rich Aromatic Compounds
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Herein, a disulfide-catalyzed electrophilic iodination of aromatic compounds using 1,3-diiodo-5,5-dimethylhydantoin (DIH) has been developed. The disulfide activates DIH as a Lewis base to promote the iodination reaction in acetonitrile under mild conditions. This system is applicable to a wide range of electron-rich aromatic compounds, including acetanilide, anisole, imidazole, and pyrazole derivatives.
- Iida, Keisuke,Ishida, Shunsuke,Watanabe, Takamichi,Arai, Takayoshi
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- Disulfide-Catalyzed Iodination of Electron-Rich Aromatic Compounds
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Herein, a disulfide-catalyzed electrophilic iodination of aromatic compounds using 1,3-diiodo-5,5-dimethylhydantoin (DIH) has been developed. The disulfide activates DIH as a Lewis base to promote the iodination reaction in acetonitrile under mild conditions. This system is applicable to a wide range of electron-rich aromatic compounds, including acetanilide, anisole, imidazole, and pyrazole derivatives.
- Iida, Keisuke,Ishida, Shunsuke,Watanabe, Takamichi,Arai, Takayoshi
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p. 7411 - 7417
(2019/06/18)
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- INDOLE DERIVATIVES FOR THE PREVENTION AND/OR TREATMENT OF DIABETES AND ASSOCIATED METABOLIC DISORDERS
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The invention relates to substituted heterocyclic indole derivatives of Formula (I), which act as activators of the AMP-activated protein kinase (AMPK) and to the use of them for the treatment and prevention of diseases or disorders regulated by AMPK. As
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Paragraph 0133
(2017/10/26)
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- Palladium nanoparticles on graphite oxide: A recyclable catalyst for the synthesis of biaryl cores
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The synthesis of life saving drug molecules in a cost-effective and environmentally benign pathway is of paramount significance. We present an environment friendly protocol to prepare core moieties of top selling drug molecules such as boscalid and telmisartan using Suzuki-Miyaura coupling conditions. In contrast to the traditional synthesis of these pharmaceutically important molecules, we have accomplished a graphite oxide (GO) supported palladium nanoparticles (PdNPs) based catalyst which quantitatively produced these core biaryl moieties of top selling drug molecules in a recyclable way. The catalytic activity remained unchanged even after 16 successive catalytic cycles without incorporating any palladium metal impurity in the pharmaceutically significant organic products. A detailed study including IR spectroscopy, solid state NMR spectroscopy, X-ray photoelectron spectroscopy, and DFT calculation was employed to understand the role of solid support on the nondecaying recycling ability of the catalyst during the Suzuki-Miyaura coupling reaction. The study indicates a strong chemical interaction of the different functionalities present in the GO, with the palladium centers which is primarily responsible for such sustained catalytic activity during the consecutive Suzuki-Miyaura coupling cycles.
- Santra, Subhankar,Hota, Pradip Kumar,Bhattacharyya, Rangeet,Bera, Parthasarathi,Ghosh, Prasenjit,Mandal, Swadhin K.
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p. 2776 - 2789
(2014/01/06)
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- Synthesis of chromeno[3,4-b]indoles as Lamellarin D analogues: A novel DYRK1A inhibitor class
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A library of substituted chromeno[3,4-b]indoles was developed as Lamellarin isosters. Synthesis was achieved from indoles after a four-step pathway sequence involving C-3 iodination, a Suzuki cross-coupling reaction, and a one pot deprotection/lactonisation step. Twenty final compounds were tested in order to determine their activity against topoisomerase I and kinases, the two major biological activities of Lamellarins. One newly synthesized derivative exhibited a strong topoisomerase activity comparable to reference compounds such as campthotecin and Lamellarin with only a weak kinase inhibition. Two other lead compounds were identified as new nanomolar DYRK1A inhibitors and several other drugs affected the kinases in the sub-micromolar range. These results will enable us to use the chromeno[3,4-b]indole as a pharmacophore to develop potent treatments for neurological or oncological disorders in which DYRK1A is fully involved.
- Neagoie, Cleopatra,Vedrenne, Emeline,Buron, Frédéric,Mérour, Jean-Yves,Rosca, Sorin,Bourg, Stéphane,Lozach, Olivier,Meijer, Laurent,Baldeyrou, Brigitte,Lansiaux, Amelie,Routier, Sylvain
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experimental part
p. 379 - 396
(2012/04/10)
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- Regioselective copper-mediated synthesis of thieno[2,3- c ]pyrane-7-one, Indolo[2,3- c ]pyrane-1-one, and indolo[3,2- c ]pyrane-1-one
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In the presence of copper(I) iodide, heteroaromatic Β-iodo-α, Β-unsaturated carboxylic acid systems opposed to terminal alkyne afford selectively 6-endo-dig cyclization products via a tandem coupling oxacyclization reaction.
- Inack Ngi, Samuel,Guilloteau, Vincent,Abarbri, Mohamed,Thibonnet, Jerome
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supporting information; experimental part
p. 8347 - 8354
(2011/12/04)
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- New C5-alkylated indolobenzazepinones acting as inhibitors of tubulin polymerization: Cytotoxic and antitumor activities
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A series of 5-alkylindolobenzazepin-7-ones was synthesized by Suzuki coupling between 3-iodoindole-2-carboxylates and the appropriate α-alkylbenzylamino α-boronic acids followed by cyclization to the lactam. Derivatives having a linear alkyl chain at C5 were found to be highly cytotoxic to KB cells with IC50 values in the 30-80 nM range. These compounds also inhibited the polymerization of tubulin with IC50's of 1-2 μM. Compound 4f ((S)-5-ethyl) showed comparable antiproliferative activities (IC50's of 30-70 nM) in a variety of cancer cell lines, cell growth being arrested at the G2/M phase. Compound 4f induced apoptosis in a dose-dependent manner in three different cancer cell lines and was shown to affect cell morphology in a manner consistent with its inhibitory action on tubulin polymerization. Using the experimental model of glioma grafted on the chick chorio-allantoic membrane, local treatment with compound 4f markedly reduced tumor progression.
- Keller, Laurent,Beaumont, Stéphane,Liu, Jian-Miao,Thoret, Sylviane,Bignon, Jér?me S.,Wdzieczak-Bakala, Joanna,Dauban, Philippe,Dodd, Robert H.
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experimental part
p. 3414 - 3421
(2009/05/26)
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- Synthesis of indolobenzazepinones by application of an isocyanide-based multicomponent reaction
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Application of a Ugi multicomponent reaction to oxo acids 4 allows the formation of potentially antimitotic indolobenzazepinones of type 5 in good yields of up to 72%, whereas the same transformation from the starting substrate 6 gives access to analogues of paullone with yields of up to 89%. The reaction could be applied to a wide range of isocyanides, thereby ensuring introduction of molecular diversity at the key C-5 position. Use of cyclohexenyl isocyanide allows post-condensation modifications, while careful choice of the amine and the indole protecting groups proved to be important for providing the deprotected compounds necessary for biological tests. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Beaumont, Stephane,Retailleau, Pascal,Dauban, Philippe,Dodd, Robert H.
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scheme or table
p. 5162 - 5175
(2009/05/07)
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- Oxidative rearrangement of Indoles: A new approach to the EFHG-tetracyclic core of diazonamide A
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(Chemical Equation Presented) A new approach to the ring EFHG-tetracyclic core fragment of the marine secondary metabolite diazonamide A is described. The route is based on the oxidative rearrangement of 3-arylindole-2-carboxylates. Thus, a range of 3-arylindole-2-carboxylates (3, 8) underwent rearrangement to the corresponding 3,3-disubstituted oxindoles (4, 9) with migration of the ester group upon treatment with tert-butyl hypochlorite followed by acid. The oxindoles 9 with a 3-[2-(4-methoxybenzyloxy)]phenyl substituent underwent cyclization to the tetracyclic aminals 11 following N-protection, reduction, and treatment with methanesulfonic anhydride. The methodology was applied to the tyrosine-indole derivative 17 to give the EFHG-tetracyclic core of diazonamide A.
- Poriel, Cyril,Lachia, Mathilde,Wilson, Claire,Davies, James R.,Moody, Christopher J.
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p. 2978 - 2987
(2008/02/01)
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- Fluorous-tagged indolylboron for the diversity-oriented synthesis of biologically-attractive bisindole derivatives
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The diversity-oriented synthesis of bisindole derivatives to construct concise libraries using consecutive cross-coupling reactions and prepare new sulfonamide type fluorous protecting groups is presented. The Royal Society of Chemistry 2006.
- Kasahara, Takahiro,Kondo, Yoshinori
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p. 891 - 893
(2008/02/08)
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- Thio-substituted tricyclic and bicyclic aromatic methanesulfinyl derivatives
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The present invention is related to chemical compositions, processes for the preparation thereof and uses of the composition. Particularly, the present invention relates to compositions of compounds of Formula (A): wherein Ar, Y, R1 and q are as defined herein; and their use in the treatment of diseases, including treatment of sleepiness, promotion of wakefulness, treatment of Parkinson's disease, cerebral ischemia, stroke, sleep apneas, eating disorders, stimulation of appetite and weight gain, treatment of attention deficit hyperactivity disorder ("ADHD"), enhancing function in disorders associated with hypofunctionality of the cerebral cortex, including, but not limited to, depression, schizophrenia, fatigue, in particular, fatigue associated with neurologic disease, such as multiple sclerosis, chronic fatigue syndrome, and improvement of cognitive dysfunction.
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Page/Page column 33
(2008/06/13)
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- 3-substituted indole antiproliferative angiogenesis inhibitors
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3-Substituted indole carbohydrazides having the formula are useful for inhibiting angiogenesis and cell proliferation. Also disclosed are compositions which inhibit angiogenesis and cell proliferation and methods of inhibiting angiogenesis and cancer in a mammal.
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- Palladium-Catalyzed Coupling Reaction of 3-Iodoindoles and 3-Iodobenzothiophene with Terminal Acetylenes
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The palladium-catalyzed coupling reaction of 3-iodoindoles possessing an electron-withdrawing group at the 1- or 2-position with terminal acetylenes smoothly proceeded to yield 3-ethynylindoles.Similarly, the reaction of 3-iodobenzothiophene gave the e
- Sakamoto, Takao,Nagano, Tatsuo,Kondo, Yoshinori,Yamanaka, Hiroshi
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p. 2248 - 2252
(2007/10/02)
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