- Synthesis of Azepino[1,2-a]indole-10-amines via [6+1] Annulation of Ynenitriles with Reformatsky Reagent
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Lewis acid-catalyzed [6+1] annulation reactions of 2-cyano-1-propargyl- and 2-alkynyl-1-cyanomethyl-indoles with Reformatsky reagent are described. 8-Aryl, 8-alkyl-, 8-hetaryl-, 9-aryl, and 9-alkyl-azepino[1,2-a]indole amines were obtained through a 7-endo-mode cyclization of the β-aminoacrylate intermediates. The antiproliferative activity of the azepino[1,2-a]indoles analogs against the HCT-116 cells were also examined.
- Iioka, Ryoya,Yorozu, Kohei,Sakai, Yoko,Kawai, Rika,Hatae, Noriyuki,Takashima, Katsuki,Tanabe, Genzoh,Wasada, Hiroaki,Yoshimatsu, Mitsuhiro
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supporting information
p. 1553 - 1558
(2021/02/26)
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- SPIROCYCLE COMPOUNDS AND METHODS OF MAKING AND USING SAME
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Provided herein are compounds and compositions useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.
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Paragraph 00219
(2019/03/17)
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- Preparation method for 4,6-dichloroindole
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The invention discloses a preparation method for 4,6-dichloroindole. The preparation method comprises the following specific steps: in an acidic condition of 3,5-dichloroaniline, carrying out a diazo-reaction on sodium nitrite and then carrying out a condensation reaction with ethyl pyruvate to obtain ethyl-2-(2-(3,5-dichlorophenyl) hydrazono) propionic acid; carrying out ring formation on the ethyl-2-(2-(3,5-dichlorophenyl) hydrazono) propionic acid under the action of lewis acid to obtain 4,6-dichlorindole ethyl formate; hydrolyzing the 4,6-dichlorindole ethyl formate under action of lithium hydroxide to obtain 4,6-dichloroindolecarboxylic acid; and carrying out decarboxylation on the 4,6-dichloroindolecarboxylic acid to obtain 4,6-dichloroindole. The synthetic process of the inventionis more economic, environmentally friendly, efficient and simple.
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- Preparation method and application of indolo pyridone compounds with antitumor activity
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The invention discloses a preparation method and an application of indolo pyridone compounds with antitumor activity, and belongs to the technical field of medicine synthesis. The technical scheme ischaracterized in that the structural formula of the indo
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- Novel indolopyridone drug molecule as well as preparation method and application thereof
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The invention discloses a novel indolopyridone drug molecule as well as a preparation method and application thereof and belongs to the technical field of pharmaceutical synthesis. According to the technical scheme provided by the invention, the novel ind
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- Remarkable Enhancement in Boron Uptake Within Glioblastoma Cells With Carboranyl–Indole Carboxamides
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Novel boron-rich, carboranyl–indole carboxamide ligands were prepared and found to effectively target the 18 kDa translocator protein (TSPO), an upregulated mitochondrial membrane-bound protein which has been observed in variety of tumor cell lines and its expression appears to be proportional to the degree of tumorigenicity, emphasizing a key role in cancer cell proliferation. Both boronated compounds displayed remarkably high affinities for the TSPO. In addition, the in vitro uptake of these compounds into T98G human glioma cells was found to be 25- to 100-fold greater than that of clinical boron neutron capture therapy (BNCT) agents.
- Narlawar, Rajeshwar,Austin, Christopher J. D.,Kahlert, Jan,Selleri, Silvia,Da Pozzo, Eleonora,Martini, Claudia,Werry, Eryn L.,Rendina, Louis M.,Kassiou, Michael
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p. 3321 - 3327
(2018/11/02)
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- Environmentally friendly method for preparing 4,6-dihalogen-substituted indole-2-ethyl formate
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The invention discloses a preparation method of 4,6-dihalogen-substituted indole-2-ethyl formate, the preparation method is characterized in that ethyl pyruvate-3,5-dihalophenylhydrazone is used as araw material for cyclizing in a polyphosphoric acid and toluene mixed solvent system to form 3,5-dihalogen-substituted indole-2-ethyl formate, and the target compound is isolated by liquid-liquid extraction of a reaction mixture. The method is simple in operation, free of waste water discharge, green, environmentally friendly and suitable for industrial production.
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Paragraph 0020; 0021; 0029; 0030
(2018/11/03)
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- From Cells to Mice to Target: Characterization of NEU-1053 (SB-443342) and Its Analogues for Treatment of Human African Trypanosomiasis
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Human African trypanosomiasis is a neglected tropical disease that is lethal if left untreated. Existing therapeutics have limited efficacy and severe associated toxicities. 2-(2-(((3-((1H-Benzo[d]imidazol-2-yl)amino)propyl)amino)methyl)-4,6-dichloro-1H-indol-1-yl)ethan-1-ol (NEU-1053) has recently been identified from a high-throughput screen of >42,000 compounds as a highly potent and fast-acting trypanocidal agent capable of curing a bloodstream infection of Trypanosoma brucei in mice. We have designed a library of analogues to probe the structure-activity relationship and improve the predicted central nervous system (CNS) exposure of NEU-1053. We report the activity of these inhibitors of T. brucei, the efficacy of NEU-1053 in a murine CNS model of infection, and identification of the target of NEU-1053 via X-ray crystallography.
- Devine, William G.,Diaz-Gonzalez, Rosario,Ceballos-Perez, Gloria,Rojas, Domingo,Satoh, Takashi,Tear, Westley,Ranade, Ranae M.,Barros-álvarez, Ximena,Hol, Wim G. J.,Buckner, Frederick S.,Navarro, Miguel,Pollastri, Michael P.
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p. 225 - 236
(2017/04/21)
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- Discovery of 3-Substituted 1H-Indole-2-carboxylic Acid Derivatives as a Novel Class of CysLT1 Selective Antagonists
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The indole derivative, 3-((E)-3-((3-((E)-2-(7-chloroquinolin-2yl)vinyl)phenyl)amino)-3-oxoprop-1-en-1-yl)-7-methoxy-1H-indole-2-carboxylic acid (17k), was identified as a novel and highly potent and selective CysLT1 antagonist with IC50 values of 0.0059 ± 0.0011 and 15 ± 4 μM for CysLT1 and CysLT2, respectively.
- Chen, Huayan,Yang, Hui,Wang, Zhilong,Xie, Xin,Nan, Fajun
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p. 335 - 339
(2016/03/25)
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- INDOLE CARBOXAMIDE DERIVATIVES AND USES THEREOF
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A compound of Formula (I) is provided that has been shown to be useful for treating a disease, disorder or syndrome that is mediated by the transportation of essential molecules in the mmpL3 pathway: (I) wherein R1, R2, R3, R4, R5 and R6 are as defined herein.
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- Development of [3H]2-carboxy-4,6-dichloro-1 H -indole-3-propionic acid ([3H]PSB-12150): A useful tool for studying GPR17
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The recently described synthetic GPR17 agonist 2-carboxy-4,6-dichloro-1H- indole-3-propionic acid (1) was prepared in tritium-labeled form by catalytic hydrogenation of the corresponding propenoic acid derivative 8 with tritium gas. The radioligand [3H]PSB-12150 (9) was obtained with a specific activity of 17 Ci/mmol (629 GBq/mmol). It showed specific and saturable binding to a single binding site in membrane preparations from Chinese hamster ovary cells recombinantly expressing the human GPR17. A competition assay procedure was established, which allows the determination of ligand binding affinities.
- Koese, Meryem,Ritter, Kirsten,Thiemke, Katharina,Gillard, Michel,Kostenis, Evi,Mueller, Christa E.
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p. 326 - 330
(2014/05/06)
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- Synthesis, labelling and evaluation of hydantoin-substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of the glycine binding site of the N-methyl- d -aspartate receptor
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The N-methyl- d-aspartate (NMDA) receptor as a type of ionotropic glutamatergic receptors is essential for physiological processes such as learning, memory and synaptic plasticity. A glutamate-induced overactivation of these receptors, accompanied by increased intracellular calcium concentration, causes cell injury and leads to a large number of acute or chronic neurological disorders, such as stroke, trauma, Parkinson's disease and Alzheimer's disease. In an attempt to visualise the glutamatergic neurotransmission in vivo with positron emission tomography, novel fluoroethoxy- and methoxy-substituted reference compounds based on the lead structure of a hydantoin-substituted indole-2-carboxylic acid were synthesised. The affinities towards the glycine binding site of the NMDA receptor showed Ki values between 322 and 11 nM and the lipophilicities ranged from logD values of 1.51 to 2.53. On the basis of these results, precursor compounds were synthesised containing a phenolic hydroxy moiety to obtain the radiolabelled ligands through an alkylation reaction. Radiosynthesis was achieved by labelling the precursor ethyl 4,6-dichloro-3-((3-(4-hydroxyphenyl)-2,4-dioxoimidazolidin-1-yl)methyl)- indole-2-carboxylate with 2-[18F]fluoroethyl tosylate or [ 11C]methyl iodide and subsequent cleavage of the ethyl ester moiety. This gave the final products in overall decay-corrected radiochemical yields of 5-7% and 6-9% and specific activities of 24-67 GBq/μmol and 8-26 GBq/μmol, respectively. Copyright
- Bauman,Piel,Hoehnemann,Krauss,Jansen,Solbach,Dannhardt,Roesch
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experimental part
p. 645 - 656
(2012/01/06)
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- SUBSTITUTED INDOLE COMPOUND
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Disclosed is an excellent LXR modulator. A compound represented by the general formula (I): (I) wherein R1, R2, R3 and R4: H, an alkyl which may be substituted, OH, an alkoxy which may be substituted, an amino which may be substituted, a halogeno, a phenyl or the like; R5: H or an alkyl; R6: -COR8 (wherein R8: an alkoxy which may be substituted, a phenyloxy which may be substituted, an amino which may be substituted, or the like), -SO2R9 (wherein R9: an alkyl which may be substituted, a phenyl which may be substituted or a heterocyclyl which may be substituted), or an alkyl which may be substituted; R7: -X2R10 [wherein R10: -COR11 (where R11: OH, an alkoxy which may be substituted or an amino which may be substituted), -SO2R12 (where R12: an alkyl which may be substituted or amino which may be substituted), -N(R13)COR14 (where R13: H or an alkyl which may be substituted; R14: H or an alkyl which may be substituted), -N(R13)SO2R15 (where R13: as defined above; R15: an alkyl which may be substituted) or tetrazol-5-yl; and X2: a single bond or an alkylene which may be substituted]; X1: a methylene which may be substituted; Y1: a phenyl which may be substituted or a heterocyclyl which may be substituted; and Y2: an aryl which may be substituted, a heterocyclyl which may be substituted or the like], or the like.
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- NMDA (N-METHYL-D-ASPARTATE) ANTAGONISTS
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The present invention is new excitatory amino acid antagonists (herein referred to as compounds of formula (1)). These new antagonists are useful as NMDA (N-methyl-D-aspartate) antagonists.
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Page/Page column 15
(2010/02/14)
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- Chemical development of MDL 103371: An N-methyl-D-aspartate-type glycine receptor antagonist for the treatment of stroke
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MDL 103371 is a N-methyl-D-aspartate (NMDA)-type glycine receptor antagonist for the potential treatment of stroke. Evaluation of five different synthetic routes, which included Stille, Suzuki, enol ether, Knoevenagel, and the Mukaiyama coupling reactions
- Watson, Timothy J.N.,Horgan, Stephen W.,Shah, Ramnik S.,Farr, Robert A.,Schnettler, Richard A.,Nevill Jr., C. Richard,Weiberth, Franz J.,Huber, Edward W.,Baron, Bruce M.,Webster, Mark E.,Mishra, Rajesh K.,Harrison, Boyd L.,Nyce, Phillip L.,Rand, Cynthia L.,Goralski, Christian T.
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p. 477 - 487
(2013/08/07)
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- 3-(indol-3-yl)-propenoic acid derivatives and pharmaceutical compositions thereof
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The present invention is new 3-(indol-3-yl)-propenoic acid derivatives and pharmaceutical compositions thereof. These new 3-indolyl-3-yl-prpopenoic acid derivatives are useful as NMDA antagonist.
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