- Discovery of new indole-based 1,2,4-triazole derivatives as potent tubulin polymerization inhibitors with anticancer activity
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Thirty-six novel indole-based 1,2,4-triazole derivatives were designed and synthesized through the molecular hybrid strategy. The bioassay results revealed that 9p displayed excellent antiproliferative efficacies in the nanomolar range against HeLa cells. Importantly, the compound exhibited no obvious cytotoxic activity (IC50 > 100 μM) toward HEK-293, a normal human embryonic kidney cell line. Mechanism analysis indicated that 9p significantly arrested the cell cycle at the G2/M phase and induced apoptosis in HeLa cells in a dose-dependent manner. Further evidence demonstrated that the promising compound effectively inhibited tubulin polymerization with an IC50 value of 8.3 μM, and molecular docking studies revealed that 9p well occupied the colchicine-site in tubulin. The present study highlights that indole-triazole hybrids might be used as a promising scaffold to develop novel tubulin polymerization inhibitors for cancer treatment.
- Chen, Lin,Jian, Xie-Er,Liu, Yu-Xia,Ma, Yu-Feng,Yang, Fang,You, Wen-Wei,Zhao, Pei-Liang
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p. 21869 - 21880
(2021/12/09)
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- Development and Profiling of Inverse Agonist Tools for the Neuroprotective Transcription Factor Nurr1
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The ligand-sensing transcription factor nuclear receptor related 1 (Nurr1) evolves as an appealing target to treat neurodegenerative diseases. Despite its therapeutic potential observed in various rodent models, potent modulators for Nurr1 are lacking as pharmacological tools. Here, we report the structure-activity relationship and systematic optimization of indole-based inverse Nurr1 agonists. Optimized analogues decreased the receptor's intrinsic transcriptional activity by up to more than 90% and revealed preference for inhibiting Nurr1 monomer activity. In orthogonal cell-free settings, we detected displacement of NCoRs and disruption of the Nurr1 homodimer as molecular modes of action. The inverse Nurr1 agonists reduced the expression of Nurr1-regulated genes in T98G cells, and treatment with an inverse Nurr1 agonist mimicked the effect of Nurr1 silencing on interleukin-6 release from LPS-stimulated human astrocytes. The indole-based inverse Nurr1 agonists valuably extend the toolbox of Nurr1 modulators to further probe the role of Nurr1 in neuroinflammation, cancer, and beyond.
- Zaienne, Daniel,Willems, Sabine,Schierle, Simone,Heering, Jan,Merk, Daniel
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p. 15126 - 15140
(2021/10/25)
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- Discovery of novel indole-1,2,4-triazole derivatives as tubulin polymerization inhibitors
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A series of novel indole-1,2,4-triazole derivatives have been designed, synthesized, and evaluated as potential tubulin polymerization inhibitors. The top hit 12, bearing the 3,4,5-trimethoxyphenyl moiety, exhibited substantial anti-proliferative activity against HepG2, HeLa, MCF-7, and A549 cells in vitro with IC50 values of 0.23 ± 0.08 μM, 0.15 ± 0.18 μM, 0.38 ± 0.12 μM, and 0.30 ± 0.13 μM, respectively. It also inhibited tubulin polymerization with the IC50 value of 2.1 ± 0.12 μM, which was comparable with that of the positive controls. Furthermore, compound 12 regulated the expression of cell cycle-related proteins (Cyclin B1, Cdc25c, and Cdc2) and apoptosis-related proteins (Bcl-2, Bcl-x, and Mcl-1). Mechanistically, compound 12 could arrest cell cycle at the G2/M phase, thus induce an increase of apoptotic cell death. In addition, molecular docking hinted the possible interaction mode of compound 12 into the colchicine binding site of tubulin heterodimers. According to the applications of microtubule-targeting agents in both direct and synergistic cancer therapies, we hope this work might be of significance for future researches.
- Wu, Meng-Ke,Man, Ruo-Jun,Liao, Yan-Juan,Zhu, Hai-Liang,Zhou, Zhu-Gui
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p. 1008 - 1020
(2021/03/15)
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- Development of Bisindole-Substituted Aminopyrazoles as Novel GSK-3β Inhibitors with Suppressive Effects against Microglial Inflammation and Oxidative Neurotoxicity
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Development of glycogen synthase kinase-3β (GSK-3β) inactivation-centric agents with polypharmacological profiles is increasingly recognized as a promising therapeutic strategy against the multifactorial etiopathology of Alzheimer's disease (AD). In this respect, a series of disubstituted aminopyrazole derivatives were designed and synthesized as a new class of GSK-3β inhibitors. Most of these derivatives possess GSK-3β inhibitory activities with IC50 values in the micromolar ranges, among which bisindole-substituted aminopyrazole derivative 6h displayed moderate GSK-3β inhibition (IC50 = 1.76 ± 0.19 μM), and alleviative effects against lipopolysaccharide (LPS)-induced glial inflammation in BV-2 cells and glutamate-induced oxidative neurotoxicity in HT-22 cells. Further in vivo studies indicated that compound 6h had potent anti-inflammatory effect, by showing markedly reduced microglial activation and astrocyte proliferation in the brain of LPS-injected mice. Overall, the simultaneous modulation of 6h on multiple dysfunctions of disease network highlights this structural distinctively bisindole-substituted aminopyrazole could be a useful prototype for the discovery of novel therapeutic agents to tackle AD and other GSK-3β associated complex neurological syndromes.
- Liu, Jian-Guo,Zhao, Danfeng,Gong, Qi,Bao, Fengxia,Chen, Wen-Wen,Zhang, Haiyan,Xu, Ming-Hua
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p. 3398 - 3408
(2020/11/26)
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- Synthesis, anticancer evaluation and molecular docking studies of 2,5-bis(indolyl)-1,3,4-oxadiazoles, Nortopsentin analogues
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A series of ten novel 2,5-bis(indolyl)-1,3,4-oxadiazoles were designed and synthesized. All these compounds were evaluated for their cytotoxicity against four cancer cell lines namely A549, MDA-MB-231, MCF-7 and HeLa using MTT reduced assay. Among them, compound 12e exhibited good cytotoxicity on MCF-7 cell line with IC50 value of 1.8 μM and it was identified as a promising drug lead when compared to the standard drug doxorubicin (IC50 value 0.98 μM). Compound, 12h exhibited better antitumor activity against three cancer cell lines i.e., lung (A549), breast (MCF-7) and cervical (HeLa) with IC50 values of 3.3 μM, 2.6 μM and 6.34 μM respectively. The impact of these compounds on colchicine binding site of tubulin polymer was carefully investigated using molecular docking studies and interpretations between actives and inactive were explained.
- Sreenivasulu, Reddymasu,Tej, Mandava Bhuvan,Jadav, Surender Singh,Sujitha, Pombala,Kumar, C. Ganesh,Raju, Rudraraju Ramesh
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- Synthesis, antiproliferative and apoptosis induction potential activities of novel bis(indolyl)hydrazide-hydrazone derivatives
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In recent years, indole-indazolyl hydrazide-hydrazone derivatives with strong cell growth inhibition and apoptosis induction characteristics are being strongly screened for their cancer chemo-preventive potential. In the present study, N-methyl and N,N-dimethyl bis(indolyl)hydrazide-hydrazone analog derivatives were designed, synthesized and allowed to evaluate for their anti-proliferative and apoptosis induction potential against cervical (HeLa), breast (MCF-7 and MDA-MB-231) and lung (A549) cancer cell lines relative to normal HEK293 cells. The MTT assay in conjunction with mitochondrial potential assays and the trypan blue dye exclusion were employed to ascertain the effects of the derivatives on the cancer cells. Further, mechanistic studies were conducted on compound 14a to understand the biochemical mechanisms and functional interactions with various signaling pathways triggered in HeLa and MCF-7 cells. Compound 14a induced apoptosis via caspase independent pathway through the participation of mitogen-activated protein kinases (MAPK) such as extracellular signal related kinase (ERK) and p38 as well as p53 pathways. It originates the activation of pro-apoptotic proteins such as Bak and Mcl-1s and also strongly induced the generation of reactive oxygen species. In downstream signaling pathway, activated p53 protein interacted with MAPK pathways, including SAPK/c-Jun N-terminal protein kinase (JNK), p38 and ERK kinases resulting in apoptotic cell death. The involvement of MAPK cascades such as p38, ERK and p38 on compound 14a induced apoptotic cell death was evidenced by the fact that the inclusion of specific inhibitors of p38, ERK1/2 and JNK MAPK (SB2035809, PD98059 and SP600125) prevented the compound 14a towards induced apoptosis. The results clearly showed that MAP kinase cascades were crucial for apoptotic response in compound 14a induced cellular killing and were dependent on p53 activity. Based on the results, compound 14a was identified as a promising candidate for cancer therapeutics and these findings furnish a basis for further in vivo experiments on anti-proliferative activity.
- Sreenivasulu, Reddymasu,Reddy, Kotthireddy Thirumal,Sujitha, Pombala,Kumar, C. Ganesh,Raju, Rudraraju Ramesh
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p. 1043 - 1055
(2019/02/19)
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- Expeditious synthesis of multisubstituted indoles: Via multiple hydrogen transfers
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Described herein is the expeditious construction of multi-substituted indole skeletons via multiple hydrogen transfers. When ortho-amino ketoesters were treated with a catalytic amount of TiCl4 in the presence of 1.0 equivalent of dehydrating reagent, three types of hydrogen transfer processes ([1,5]-hydride shift, proton transfer, and [1,2]-hydride shift) occurred to give various 3-alkoxycarbonylindoles. Further study revealed that a [1,2]-alkyl shift instead of a [1,2]-hydride shift proceeded to afford 3-alkylindoles from the substrates with an amino group having tertiary carbons adjacent to a nitrogen atom.
- Yoshida, Taira,Mori, Keiji
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supporting information
p. 12686 - 12689
(2018/11/23)
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- Synthesis, anticancer evaluation and molecular docking studies of bis(indolyl) triazinones, Nortopsentin analogs
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Abstract: A new series of bis indolyl tri keto diazo compounds and 3,5-bis(3′-indolyl) triazinones were designed and synthesized as anticancer agents. Their anticancer activity was screened in vitro towards four different human cancer cell lines like HeLa, MCF-7, MDA-MB-231 and A549 cell lines. Among them, compounds 17a and 17b showed potent cytotoxicity with inhibition (IC50) values of 4.6 and 1.3?μM on Human Cervical cancer cell line, respectively. The in silico simulation studies using ADT 1.5.6 tools revealed unique interactions of indole ring of compound 17b with colchicines active site residue Tyr312 could be a valid reason behind its maximum potency when compared to remaining compounds in responsible of its higher activity.
- Sreenivasulu, Reddymasu,Durgesh, Rudavath,Jadav, Surender Singh,Sujitha, Pombala,Ganesh Kumar,Raju, Rudraraju Ramesh
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p. 1369 - 1378
(2018/06/01)
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- Design, synthesis and application of pyrazole-skeleton-containing indole derivative antitumor compound
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The invention discloses an indole derivative containing a pyrazole skeleton as well as a preparation method and application thereof. The structure of the indole derivative containing the pyrazole skeleton is described in the specification, wherein R1 is selected from H and CH3; and R2 is selected from -CH3, -CH2CH3 and a chemical group (described in the specification).
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-
Paragraph 0029
(2018/04/26)
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- Derivatives containing 1,2,4-triazole framework and preparation method and application thereof
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The invention discloses derivatives containing a 1,2,4-triazole framework and a preparation method and application thereof. The structural formula of the derivatives containing formula 1,2,4-triazole framework is as shown in the specification, where R1 is selected from -H, -F, -Cl and -Br; R2 is selected from -H, -OCH3, -Cl, -Br and -F; R3 is selected from -H, -OCH3, -Cl, -Br, -F, -CH3, -I and -CF3; R4 is selected from -H and -OCH3; and R5 is selected from -H and -F. The synthetic method disclosed by the invention is simple in process, involves few steps, is relatively low in cost, efficient and simple, has good universality and can be produced in batches.
- -
-
Paragraph 0039; 0049; 0057; 0058
(2017/09/01)
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- Thermolysis of 2-diazo-3-aryl ketoesters: New route to α-aryl malonates and aromatic esters
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Thermochemical excitation enabled efficient α-aryl malonates synthesis from 2-diazo-3-aryl ketoesters and alcohols under transition metal-free reaction conditions. Furthermore, an unusual C[sbnd]C bond cleavage and C[sbnd]O/(N) bond formation occurred whe
- Zhang, Zhao,Tang, Mengyao,Zang, Lei,Zou, Liang-Hua,Li, Jie
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supporting information
p. 5681 - 5684
(2016/11/28)
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- Synthesis and functionalization of some new pyridazino[4,5-b]indole derivatives
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Starting from the indole-fused pyridazinone 5, a series of new pyridazino[4,5-b]indoles o potential pharmaceutical interest (9-18), was prepared. Compounds 20 and 21 were obtained b nucleophilic displacement of the chlorine atom of 19. Thionation of the chloro derivative 19 gav the thione compound 23, while its reaction with sodium azide gave a tetracyclic system, namel the tetrazolopyridazinoindole 22. Dehalogenation of the chloro compound 19 gave a 3-Az analogue of the natural product, Harman.
- Radini, Ibrahim,El-Kashef, Hussein,Haider, Norbert,Farghaly, Abdel-Rahman
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p. 101 - 117
(2016/10/22)
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- Catalytic C-2 Allylation of Indoles by Electronic Modulation of the Indole Ring and its Application to the Synthesis of Functionalized Carbazoles
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We report a palladium-catalyzed C-2 allylation of indoles and subsequent cyclization of the allylated indoles. The electronic effects of chloro and ester groups that can be readily installed at the C-3 position of indoles facilitated a highly efficient C–H allylation at the C-2 position. The resulting 2-allyl-3-chloroindoles were found to be suitable substrates for benzannulation reactions with alkynes and norbornadiene as an acetylene synthon. This approach, utilizing readily available indoles, allyl acetates, and norbornadiene, allows a rapid access to complex carbazoles. (Figure presented.).
- Lee, Ju Young,Ha, Hyeri,Bae, Seri,Han, Inhyuk,Joo, Jung Min
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p. 3458 - 3470
(2016/11/13)
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- Synthesis and biological evaluation of novel indole derivatives containing sulfonamide scaffold as potential tubulin inhibitor
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Microtubule-targeted drugs play a critical role in various types of cancer therapy worldwide. In our study, a series of novel indole derivatives containing a sulfonamide scaffold were designed, synthesized and biologically evaluated as potential tubulin p
- Man, Ruo-Jun,Tang, Dan-Jie,Lu, Xiao-Yuan,Duan, Yong-Tao,Tao, Xiang-Xiang,Yang, Meng-Ru,Wang, Le-Le,Wang, Bao-Zhong,Xu, Chen,Zhu, Hai-Liang
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supporting information
p. 1759 - 1767
(2016/09/23)
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- Quinoline or quinazoline derivatives, its preparation process and its use in medicine
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The invention relates to a quinoline or quinazoline derivative, its preparation method and an application in medicines, specifically to new quinoline or quinazoline derivative as shown in a general formula (I) and its medicinal salt or a pharmaceutical composition containing the derivative and a preparation method thereof. The invention further relates to an application of the quinoline or quinazoline derivative and its medicinal salt or the pharmaceutical composition containing the derivative in the preparation of a therapeutic agent, especially a protein kinase inhibitor. Each substituent group in the general formula (I) has the same definition as in the specification.
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Paragraph 0489; 0498-0500
(2018/01/19)
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- Visible-Light-Induced Direct Photocatalytic Carboxylation of Indoles with CBr4/MeOH
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Photocatalysis enables the cascade reactions of indoles and CBr4 in MeOH through a C(sp2)-H functionalization/methanolysis sequence. The title reaction provides an efficient access to indole 2- and 3-carboxylates in a single operation (no preinstallation of protecting as well as directing groups was required) with good yields under mild reaction conditions. Shedding light on indole: The regioselective alkoxycarboxylation of indoles and heteroarenes using the CBr4/MeOH couple was accomplished through visible-light-induced photoredox catalysis. The described photocatalytic strategy features operational simplicity as well as high functional-group tolerance and represents a direct procedure to access indole carboxylates in generally moderate to good yields (see scheme).
- Yang, Qing-Qing,Marchini, Marianna,Xiao, Wen-Jing,Ceroni, Paola,Bandini, Marco
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supporting information
p. 18052 - 18056
(2015/12/24)
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- Direct carboxylation of simple arenes with CO2 through a rhodium-catalyzed C-H bond activation
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Direct carboxylation of simple arenes under atmospheric pressure of CO2 is achieved through a rhodium-catalyzed C-H bond activation without the assistance of a directing group. Various arenes such as benzene, toluene, xylene, electron-rich or electron-deficient benzene derivatives, and heteroaromatics are directly carboxylated with high TONs. This journal is
- Suga, Takuya,Mizuno, Hajime,Takaya, Jun,Iwasawa, Nobuharu
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supporting information
p. 14360 - 14363
(2015/02/19)
-
- Palladium-catalyzed oxidative cyclization of tertiary enamines for synthesis of 1,3,4-trisubstituted pyrroles and 1,3-disubstituted indoles
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A novel and efficient palladium-catalyzed intramolecular oxidative cyclization of tertiary enamines for the synthesis of 1,3,4-trisubstituted pyrroles and 1,3-disubstituted indoles has been developed. Trifluoroacetic acid plays an important role in the reaction. A series of pyrroles and indoles with substitution patterns that are not easily accessible by traditional routes were synthesized in good yields under mild conditions.
- Lian, Xiao-Li,Ren, Zhi-Hui,Wang, Yao-Yu,Guan, Zheng-Hui
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supporting information
p. 3360 - 3363
(2014/07/08)
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- Bexarotene prodrugs: Targeting through cleavage by NQO1 (DT-diaphorase)
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Bexarotene, a retinoid X receptor (RXR) agonist, is being tested as a potential disease modifying treatment for neurodegenerative conditions. To limit the peripheral exposure of bexarotene and release it only in the affected areas of the brain, we designe
- Sch?fer, Anja,Burstein, Ethan S.,Olsson, Roger
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supporting information
p. 1944 - 1947
(2014/04/17)
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- Construction of indoloquinolinones via Pd(II)-catalyzed tandem CC/CN bond formation: Application to the total synthesis of isocryptolepine
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Construction of indoloquinolinone skeleton via Pd-catalyzed tandem CC/CN bond formation has been achieved in moderate to good yields. The method was applied toward the total synthesis of the bioactive natural product isocryptolepine in good overall yields.
- Chen, Xuebing,Sun, Peng,Xu, Jinyi,Wu, Xiaoming,Kong, Lingyi,Yao, Hequan,Lin, Aijun
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supporting information
p. 7114 - 7117
(2015/01/08)
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- Copper-catalyzed methyl esterification reactions via C-C bond cleavage
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The highly effective synthesis of methyl esters from benzylic alcohols, aldehydes, or acids via copper-catalyzed C-C cleavage from tert-butyl hydroperoxide is reported in this paper for the first time. Our protocol is easily accessible and practical, making it a possible supplement for the traditional way.
- Zhu, Yan,Yan, Hong,Lu, Linhua,Liu, Defu,Rong, Guangwei,Mao, Jincheng
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p. 9898 - 9905
(2013/10/22)
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- A general method for palladium-catalyzed direct carbonylation of indole with alcohol and phenol
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A novel strategy involving a first oxidative iodination and subsequent Pd0-catalyzed carbonylation to yield indole-3-carboxylate has been developed. It showed perfect generality to indole, alcohol, and phenol. The current methodology could also be conveniently applied to the synthesis of biologically active tropisetron from simple indole and tropine.
- Lang, Rui,Shi, Lijun,Li, Dengfeng,Xia, Chungu,Li, Fuwei
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supporting information; experimental part
p. 4130 - 4133
(2012/10/07)
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- Synthesis of indole-3-carboxylic acid derivatives by Pd(0)-catalyzed intramolecular α-arylation of β-(2-iodoanilino) esters
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(Chemical Equation Presented) β-(2-Iodoanilino) esters undergo intramolecular α-arylation in the presence of Pd(PPh3) 4 and potassium phenoxide. The reaction is a useful methodology for the preparation of indole-3-carboxylic acid ester derivatives.
- Sole, Daniel,Serrano, Olga
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p. 2476 - 2479
(2008/09/18)
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- Hydroheteroarylation of alkynes under mild nickel catalysis
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Nickel complexes having a bulky tri(sec-alkyl)phosphine ligand catalyze hydroheteroarylation of alkynes at 35 °C. Selective activation of an Ar-H bond over an Ar-CN bond of N-protected 3-cyanoindoles is achieved by a proper choice of ligand and/or an N-protecting group. The catalysis is applicable to a diverse range of heteroarenes to afford cis-hydroheteroarylation products in highly chemo- and stereoselective manners. Excellent regioselectivity is observed with unsymmetrical alkynes to give the corresponding heteroaryl-substituted ethenes having a larger substituent trans to an aryl group. Copyright
- Nakao, Yoshiaki,Kanyiva, Kyalo Stephen,Oda, Shinichi,Hiyama, Tamejiro
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p. 8146 - 8147
(2007/10/03)
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- Design, synthesis, and biological activity of potent and selective inhibitors of mast cell tryptase
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A new series of novel mast cell tryptase inhibitors is reported, which features the use of an indole structure as the hydrophobic substituent on a m-benzylaminepiperidine template. The best members of this series display good in vitro activity and excellent selectivity against other serine proteases.
- Hopkins, Corey R.,Czekaj, Mark,Kaye, Steven S.,Gao, Zhongli,Pribish, James,Pauls, Henry,Liang, Guyan,Sides, Keith,Cramer, Dona,Cairns, Jennifer,Luo, Yongyi,Lim, Heng-Keang,Vaz, Roy,Rebello, Sam,Maignan, Sebastian,Dupuy, Alain,Mathieu, Magali,Levell, Julian
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p. 2734 - 2737
(2007/10/03)
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- FAB I INHIBITORS
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Compounds of the formula (I) are disclosed which are Fab I inhibitors and are useful in the treatment of bacterial infections.
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- A practical method for N-methylation of indoles using dimethyl carbonate
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A new method for N-methylation of indoles using environmentally safe and less toxic methylating reagent, dimethyl carbonate (DMC), has been developed. The effect of various functional groups on the indole ring has been investigated. This method provides the desired product in high yields with high purity and is suitable for large-scale production. This process was used successfully in a 300-gal reactor train for N-methylation of 6-nitroindole.
- Jiang, Xinglong,Tiwari, Ashish,Thompson, Maethonia,Chen, Zhihong,Cleary, Thomas P.,Lee, Thomas B. K.
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p. 604 - 608
(2013/09/07)
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- Methylation of indole compounds using dimethyl carbonate
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A process for manufacturing a methylated indole compounds of the formula: where R1is selected from the group consisting of halogen, C1-C6alkyl, C1-C6alkenyl, —OCH3, —NO2, —CHO, —CO2CH3, and —CN, and R2is selected from the group consisting of C1-C6alkyl, —CO2CH3, —CN, —CHO, —NH2, —N(C1-C6alkyl)2, —(CH2)nCOOH, and —(CH2)nCN, where n is an integer from 1 to 4, inclusive, involves reacting a compound of the formula: with dimethyl carbonate in the presence of a base or a catalyst at ambient pressure.
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- Iminoxyl radicals and stable products from the one-electron oxidation of 1-methylindole-3-carbaldehyde oximes
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The radical intermediates and the stable products formed on one-electron oxidation of 1-methylindole-3-carbaldehyde oxime 2a were compared with those of 1-methylindole-3-carboxamidine oxime 4a in aqueous solution. The dibromide radical anion generated radiolytically by pulse radiolysis reacted with both 2a and 4a >C=NOH to yield the radical cations [>C=NOH]·+, which exist in prototropic equilibria with the neutral iminoxyl radicals [>C=NO]· (pKa = 3.53 ? 0.03 and 5.01 ± 0.01 at ionic strength 0.05 M, respectively). This was confirmed by the observed primary salt-effect which accelerated the decay of the radical cations but not the iminoxyl radicals. Methylation of the N-hydroxyimino function in both 2a and 4a precluded deprotonation of the corresponding radical cations [>C=NOCH3]·+. At low concentrations of 2a and high dose rates the 2a radicals [>C=NO]· decayed bimolecularly via unstable dimers to the aldehyde >C=O, with higher concentrations and lower dose rates favouring the chain-catalysed isomerisation of the N-hydroxyimino moiety. Radicals from 4a decay bimolecularly to form unstable dimers which degrade to produce an amide, nitrile and carboxylic acid. The observed differences in the oxidation chemistry of 2a and 4a probably reflect the enhanced stabilisation of iminoxyl radicals through α-amino substitution.
- Everett, Steven A.,Naylor, Matthew A.,Stratford, Michael R.L.,Patel, Kantilal B.,Ford, Eleonora,Mortensen, Alan,Ferguson, Amanda C.,Vojnovic, Borivoj,Wardman, Peter
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p. 1989 - 1997
(2007/10/03)
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- Synthesis and biological activity of N-(aminoiminomethyl)-1H-indole carboxamide derivatives as Na+/H+ exchanger inhibitors
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A series of N-(aminoiminomethyl)-1H-indole carboxamide derivatives were synthesized and their inhibitory potencies against the Na+/H+ exchanger were measured. Variation of the carbonylguanidine group at the 2- to 7- position of the indole ring system showed that a substitution at the 2- position improved the Na+/H+ exchanger inhibitory activity the most in vitro. This led to the synthesis and evaluation of an extensive series of N- (aminoiminomethyl)-1H-indole-2-carboxamide derivatives. Derivatives having an alkyl or substituted alkyl group at the 1-position of the indole ring system showed higher levels of in vitro activities. N-(aminoiminomethyl)-1-(2- phenylethyl)-1H-indole-2-carboxamide (49) had the strongest activity.
- Kitano, Masafumi,Kojima, Atsuyuki,Nakano, Kazuhiro,Miyagishi, Akira,Noguchi, Tsuyoshi,Ohashi, Naohito
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p. 1538 - 1548
(2007/10/03)
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- Indolecarbonyl Coupling Reactions Promoted by Samarium Diiodide. Application to the Synthesis of Indole-Fused Compounds
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By the assistance of an N-sulfonyl group or a cyano group at the C-2 position, hydroxyalkylations of indole-3-carbonyls were achieved by the promotion of samarium diiodide. The indolecarbonyl coupling reactions proceeded in high stereoselectivity via chel
- Lin, Shu-Chen,Yang, Fwu-Duo,Shiue, Jiann-Shyng,Yang, Shyh-Ming,Fang, Jim-Min
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p. 2909 - 2917
(2007/10/03)
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- Preparation of 2,3-Disubstituted Indoles from Indole-3-carboxylic Acids and Amides by α-Deprotonation
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Direct deprotonations have been used to obtain the 2(α)-lithiated indole-3-carboxylate dianions 8 and 14, together with the related 2(α)-lithiated indole-3-carboxamide monoanions 18 and 20b from the parent compounds.These four intermediates are useful for
- Buttery, Cheryl D.,Jones, Richard G.,Knight, David W.
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p. 1425 - 1432
(2007/10/02)
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- A BIOMIMETIC APPROACH TO SPORIDESMINS. SYNTHESIS OF AN α,β-EPOXYTRYPTOPHAN DERIVATIVE
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The reaction of 19 - prepared efficiently from 16 - with DDQ affords 22.This epoxide may serve as a model compound to investigate the biosynthesis of sporidesmins, e.g. 1 and 2.
- Plate, Ralf,Theunisse, Annette W. G.,Nivard, Rutger J. F.,Ottenheijm, Harry C. J.
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p. 6511 - 6518
(2007/10/02)
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