- Br?nsted Acid-Catalyzed Asymmetric Friedel-Crafts Alkylation of Indoles with Benzothiazole-Bearing Trifluoromethyl Ketone Hydrates
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An efficient Br?nsted acid-catalyzed asymmetric Friedel-Crafts alkylation of indoles with benzothiazole-bearing trifluoromethyl ketone hydrates as electrophiles has been developed. The mild organocatalytic reactions proceeded well with low catalyst loading to afford a range of enantioenriched α-trifluoromethyl tertiary alcohols containing both benzothiazole and indole rings with excellent yields and enantioselectivities.
- Wang, Wei,Xiong, Wenhui,Wang, Jinping,Wang, Qiu-An,Yang, Wen
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Read Online
- A new approach to the pyrrolo[3,4-b]indole ring system
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We report an approach to the pyrrolo[3,4-b]indole ring system that involves a new synthesis of pyrrolo[3,4-b]indol-1(2H)ones, which are known precursors to pyrrolo[3,4-b]indoles. 3-Trifluoroacetylindole is prepared from indole and converted into indole carboxamides upon reaction with lithiated amines. Subsequent C-2 bromination followed by a tri-n-butyltin hydride induced 1,5-radical translocation and 5-endo-trig cyclization affords 3,4-dihydropyrrolo[3,4-b]indol-1(2H)-one which upon reduction with DIBAL by the method of Kreher gives pyrrolo[3,4-b]indole.
- Badenock, Jeanese C.,Fraser, Heidi L.,Gribble, Gordon W.
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Read Online
- Palladium-Catalyzed 2-fold C-H Activation/C-C Coupling for C4-Arylation of Indoles Using Weak Chelation
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Palladium-catalyzed weak chelation-assisted regioselective C4-arylation of indoles has been accomplished using a readily available arene at moderate temperature. The C4-arylation, weak chelating benzoyl (Bz) directing group, cross-dehydrogenative coupling (CDC), broad substrate scope, and late-stage diversifications are the important practical features.
- Basak, Shubhajit,Paul, Tripti,Punniyamurthy, Tharmalingam
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supporting information
p. 554 - 558
(2022/01/20)
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- Salicylaldehyde-Promoted Cobalt-Catalyzed C-H/N-H Annulation of Indolyl Amides with Alkynes: Direct Synthesis of a 5-HT3 Receptor Antagonist Analogue
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A cobalt-catalyzed annulation of the C(sp2)-H/N-H bond of indoloamides with alkynes assisted by 8-aminoquinoline is reported for the synthesis of six-membered indololactams. The use of salicylaldehyde as the ligand is crucial for this transformation. The protocol has a broad scope for both alkynes and indoles. Preparing an active Co complex illustrates that salicylaldehyde plays a key role in the C-H activation step. The synthetic applications are proven by the gram-scale reaction and one-step construction of the multicyclic 5-HT3 receptor antagonist.
- Huang, Mao-Gui,Shi, Shuai,Li, Ming,Liu, Yue-Jin,Liu, Yue-Jin
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supporting information
p. 7094 - 7099
(2021/09/14)
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- Discovery of a lead series of potent benzodiazepine 5-HT2C receptor agonists with high selectivity in functional and binding assays
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A series of potential new 5-HT2 receptor scaffolds based on a simplification of the clinically studied, 5-HT2CR agonist vabicaserin, were designed. An in vivo feeding assay early in our screening process played an instrumental part in the lead identification process, leading us to focus on a 6,5,7-tricyclic scaffold. A subsequent early SAR investigation provided potent agonists of the 5-HT2C receptor that were highly selective in both functional and binding assays, had good rat PK properties and that significantly reduced acute food intake in the rat.
- Dang, Huong,Feichtinger, Konrad,Frazer, John,Grottick, Andrew J.,Kasem, Michelle,Le, Minh,Lehman, Juerg,Morgan, Michael E.,Ren, Albert,Sage, Carleton R.,Schrader, Thomas O.,Semple, Graeme,Unett, David J.,Whelan, Kevin T.,Wong, Amy,Zhu, Xiuwen
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supporting information
(2020/01/22)
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- High-throughput screening of bioactive compounds via new catalytic reaction in the pooled mixture
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To increase the chances of finding new candidate molecules with medicinal properties, while expending less resource and effort, the present study used pooled substrates as starting materials. A bisindole compound that showed inhibitory activity was then isolated from the mixture, and the activity was improved by optimizing the substituents on the indole skeleton.
- Satoh, Ayano,Nishina, Yuta
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- Asymmetric Hydrogenation of Aryl Perfluoroalkyl Ketones Catalyzed by Rhodium(III) Monohydride Complexes Bearing Josiphos Ligands
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The asymmetric hydrogenation of 2,2,2-trifluoroacetophenones and aryl perfluoroalkyl ketones was developed using a unique, well-defined chloride-bridged dinuclear rhodium(III) complex bearing Josiphos-type diphosphine ligands. These complexes were prepared from [RhCl(cod)]2, Josiphos ligands, and hydrochloric acid. As catalyst precursors, they allow for the efficient and enantioselective synthesis (up to 99 % ee) of chiral secondary alcohols with perfluoroalkyl groups. This system does not require an activating base for the hydrogenation of 2,2,2-trifluoroacetophenones. Additionally, the enantioselective C=O hydrogenations of 2-phenyl-3-(haloacetyl)-indoles, a class of privileged structures in medicinal chemistry, is reported for the first time.
- Brüning, Fabian,Nagae, Haruki,K?ch, Daniel,Mashima, Kazushi,Togni, Antonio
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supporting information
p. 10818 - 10822
(2019/07/31)
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- Cell death inhibitor and novel compound
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Provided is a cell-death inhibitor including, as an active ingredient thereof, a compound represented by formula (1), and/or a compound represented by formula (2). The cell-death inhibitor exhibits high cell-death inhibition activity.
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Paragraph 0236-0237; 0247
(2018/03/13)
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- Efficient Synthesis and Biological Activity of Novel Indole Derivatives as VEGFR-2 Tyrosine Kinase Inhibitors
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A series of novel indole derivatives were synthesized as potent inhibitors for the vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase. Among those, compound 10b demonstrated the highest growth inhibition rate of 66.7% against the VEGFR-2 tyrosine kinase at 10 μM which indicates that indole-benzothiazole might be the favorable structure. The binding mode of compound 10b with VEGFR-2 tyrosine kinase was evaluated by molecular docking.
- Zhang,Xu,Wang,Kang
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p. 3006 - 3016
(2018/02/21)
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- Copper-mediated trifluoroacetylation of indoles with ethyl trifluoropyruvate
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Direct trifluoroacetylation of indoles with ethyl trifluoropyruvate as a trifluoroacetylating reagent has been developed. This novel protocol provides an attractive route for the preparation of 3-trifluoroacetylindole derivatives, due to its operational simplicity and practicability as well as mild reaction conditions.
- Yan, Guobing,Cao, Xihan,Zheng, Wanbin,Ke, Qiumin,Zhang, Jieyu,Huang, Dayun
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supporting information
p. 5904 - 5907
(2017/07/25)
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- Synthesis method for 3-(trifluoroacetyl)indole derivative
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The invention discloses a synthesis method for a 3-(trifluoroacetyl)indole derivative and belongs to the technical field of organic synthesis intermediates. The method particularly includes the following steps: 1) feeding dimethyl sulfoxide, an indole derivative, ethyl trifluoropyruvate and cuprous chloride into a pressure-resistant reaction tube, tightly screwing a plug of the reaction tube, and performing a magnetic-stirring reaction for 12 h in oil bath at 80 DEG C; 2) when the reaction is finished, performing extraction with ethyl ether and mixing organic phases, performing pressure reduced evaporation to remove most of the solvent, and performing column chromatography separation and purification to residual mixture liquid with petroleum ether and ethyl acetate, volume ratio being 5:1-10:1, as a leaching liquid, thereby producing the product. The 3-(trifluoroacetyl)indole derivative has wide applications in the fields such as medicines, pesticides, etc. The synthesis method is low in cost, has simple operations and high yield, and has excellent application prospect.
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Page/Page column 4
(2017/08/31)
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- Friedel-Crafts Fluoroacetylation of Indoles with Fluorinated Acetic Acids for the Synthesis of Fluoromethyl Indol-3-yl Ketones under Catalyst- and Additive-Free Conditions
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A simple and efficient protocol for the fluoroacetylation of indoles is reported. The reaction uses fluorinated acetic acids as the fluoroacetylation reagents to synthesize diverse fluoromethyl indol-3-yl ketones in good yields under catalyst- and additive-free conditions. In addition, the only byproduct is water in this transformation. The synthetic utility of this reaction was also demonstrated by the concise synthesis of α-(trifluoromethyl)(indol-3-yl)methanol and indole-3-carboxylic acid.
- Yao, Shun-Jiang,Ren, Zhi-Hui,Wang, Yao-Yu,Guan, Zheng-Hui
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p. 4226 - 4234
(2016/06/09)
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- Catalytic highly enantioselective transfer hydrogenation of β-trifluoromethyl nitroalkenes. An easy and general entry to optically active β-trifluoromethyl amines
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In the presence of a thiourea catalyst, β-CF3 nitroalkenes react with Hantzsch esters in a highly enantioselective fashion, giving a broad range of β-CF3 amine precursors with a tertiary stereocentre at the β-position. This reaction
- Martinelli, Emilie,Vicini, Anna Chiara,Mancinelli, Michele,Mazzanti, Andrea,Zani, Paolo,Bernardi, Luca,Fochi, Mariafrancesca
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supporting information
p. 658 - 660
(2015/01/09)
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- 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE
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Provided are 5-HT2C receptor agonists. Also provided are methods for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea. Also provided are compositions comprising a selective 5-HT2C receptor agonist, optionally in combination with a supplemental agent, and methods for reducing the frequency of smoking tobacco in an individual attempting to reduce frequency of smoking tobacco; aiding in the cessation or lessening of use of a tobacco product in an individual attempting to cease or lessen use of a tobacco product; aiding in smoking cessation and preventing associated weight gain; controlling weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; reducing weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; treating nicotine dependency, addiction and/or withdrawal in an individual attempting to treat nicotine dependency, addiction and/or withdrawal; or reducing the likelihood of relapse use of nicotine by an individual attempting to cease nicotine use comprising administering a selective 5-HT2C receptor agonist, optionally in combination with a supplemental agent.
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Page/Page column 212
(2015/05/19)
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- Synthesis, Stability, and Photoreactivity of Diazirinyl-Substituted N-Heterocycles Based on Indole, Benzimidazole, and Imidazole
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The synthesis, thermal stability, and photoreactivity of trifluoromethyl diazirines installed at the heterocyclic section of N-methylindole, N-methylbenzimidazole, and at N-methylimidazole were investigated. N-Tosyl-3-diazirinylindole and N-methyl-2-diazirinylbenzimidazole proved to be thermally stable, whereas the corresponding 2-diazirinylindole was not. The least stable was 2-diazirinylimidazole, which underwent rapid decomposition. Quenching with ethanol indicated that the corresponding carbene was formed. Decomposition is rationalized by exothermic coarctate ring-opening of the carbene. Quantum mechanical calculations [B3LYP/6-311G(2d,2p)] predict singlet ground states of all carbenes. Accordingly, Friedel-Crafts alkylation products were formed on irradiation (350 nm, Rayonet) of the N-methylbenzimidazole-based diazirine in the presence of phenol.
- Raimer, Bj?rn,Wartmann, Thomas,Jones, Peter G.,Lindel, Thomas
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p. 5509 - 5520
(2014/10/15)
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- Mixed-Metal MIL-100(Sc,M) (M=Al, Cr, Fe) for Lewis acid catalysis and tandem C-C Bond formation and alcohol oxidation
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The trivalent metal cations Al3+, Cr3+, and Fe3+ were each introduced, together with Sc3+, into MIL- 100(Sc,M) solid solutions (M=Al, Cr, Fe) by direct synthesis. The substitution has been confirmed by powder X-
- Mitchell, Laura,Williamson, Patrick,Ehrlichov, Barbora,Anderson, Amanda E.,Seymour, Valerie R.,Ashbrook, Sharon E.,Acerbi, Nadia,Daniels, Luke M.,Walton, Richard I.,Clarke, Matthew L.,Wright, Paul A.
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supporting information
p. 17185 - 17197
(2015/02/19)
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- S1P RECEPTORS MODULATORS AND THEIR USE THEREOF
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The invention relates to novel compounds that have S1P receptor modulating activity. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, autoimmune response. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as autoimmune response.
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Page/Page column 65
(2010/04/30)
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- S1P RECEPTORS MODULATORS
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The invention relates to novel compounds that have S1P receptor modulating activity and, preferably, apoptotic activity and/or anti proliferative activity against cancer cells and other cell types. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, cancer. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as cancer.
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Page/Page column 59
(2010/04/30)
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- Synthesis and anticancer activity of 5-(3-indolyl)-1,3,4-thiadiazoles
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A series of 5-(3-indolyl)-2-substituted-1,3,4-thiadiazoles 5a-m were synthesized and their cytotoxicity analyzed against six human cancer cell lines. The reaction of indole-3-carboxylic acid 3 with aryl or heteroaryl hydrazides afforded the N,N′-diacylhydrazines 4, which upon treatment with Lawesson's reagent resulted in the formation of indolyl-1,3,4-thiadiazoles 5a-m in good yields. Indolyl-1,3,4-thiadiazole 5m with 4-benzyloxy-3-methoxyphenyl and 5-bromo indolyl substituents is the most active in suppressing the growth of cancer cells (IC50 1.5 μM, PaCa2). The compounds 5b, 5e and 5h bearing C-2 substituent as benzyl, 3,4-dimethoxyphenyl and 4-benzyloxy-3- methoxyphenyl, respectively, have shown significant cytotoxicity against multiple cancer cell lines. Introduction of 4-dimethylamino (5d and 5k) and 3,4,5-trimethoxy (5l) groups in the C-2 phenyl ring induced selectivity against MCF7 and MDA-MB-231 cancer cell lines (compounds 5d, 5k and 5l).
- Kumar, Dalip,Maruthi Kumar,Chang, Kuei-Hua,Shah, Kavita
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scheme or table
p. 4664 - 4668
(2010/10/03)
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- Preparation of indole-phosphine oxazoline (IndPHOX) ligands and their application in allylic alkylation
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Two classes of indole-phosphine oxazoline ligands have been prepared from readily available starting materials in good overall yields. These modular ligands include an indole skeleton with either a phosphine moiety or an oxazoline ring at the 2- or 3-position, respectively. The utility of these ligands was demonstrated in a catalytic asymmetric reaction: the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate was performed with enantioselectivities as high as 98%.
- Wang, Yu,Haemaelaeinen, Antti,Tois, Jan,Franzen, Robert
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experimental part
p. 2376 - 2384
(2010/12/25)
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- NOVEL P2X7R ANTAGONISTS AND THEIR USE
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The present application is directed to novel P2X7R antagonists that are indol-3-carboxamide or azaindole-3-carboxamide compounds, pharmaceutical compositions comprising the same and their use for the prophylactic or therapeutic treatment of diseases mediated by P2X7R activity.
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Page/Page column 11; 13
(2009/12/27)
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- Synthesis and structure-activity relationship of 1H-indole-3-carboxylic acid pyridine-3-ylamides: A novel series of 5-HT2C receptor antagonists
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A novel series of 1H-indole-3-carboxylic acid pyridine-3-ylamides were synthesized and identified to show high affinity and selectivity for 5-HT2C receptor. Among them, 1H-indole-3-carboxylic acid[6-(2-chloro-pyridin-3-yloxy)-pyridin-3-yl]-amide (15k) exhibits the highest affinity (IC50 = 0.5 nM) with an excellent selectivity (>2000 times) over other serotonin (5-HT1A, 5-HT2A, and 5-HT6) and dopamine (D2-D4) receptors.
- Park, Chul Min,Kim, So Young,Park, Woo Kyu,Park, No Sang,Seong, Churl Min
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supporting information; experimental part
p. 3844 - 3847
(2009/04/16)
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- N-(hetero)aryl indole derivatives as pesticides
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The invention relates to compounds of the general formula wherein R1, R2, R3, R4, R5, R6, A, X, m and n have the significances given in claim 1, and optionally the enantiomers thereof. The
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Page/Page column 23
(2008/06/13)
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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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- 3-Acylindoles via a one-pot, regioselective Friedel-Crafts reaction
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Within we report a general one-pot high-yielding Friedel-Crafts acylation of indole using acid chlorides and diethylaluminum chloride in gram scale quantities. This general synthesis affords products that are easily isolated and require no complex purification procedures.
- Wynne, James H.,Lloyd, Christopher T.,Jensen, Samuel D.,Boson, Sean,Stalick, Wayne M.
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p. 2277 - 2282
(2007/10/03)
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- Fungicides for the control of take-all disease of plants
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Plant disease caused by soil-borne fungus Gaeumannonyces graminis (Gg) is controlled by applying to the seed or the soil a fungicide which has the following general formula: STR1
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- Synthesis of indole-3-carboxamides via a haloform cleavage reaction of 3-trifluoroacetylindole with lithium dialkylamides
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Reaction of 3-trifluoroacetylindole (4) with lithium dialkylamides affords the corresponding indole-3-carboxamides (5) in good to excellent yields.
- Hassinger, Heidi L.,Soll, Richard M.,Gribble, Gordon W.
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p. 3095 - 3098
(2007/10/03)
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- 1,3-OXAZIN-6-ONES: VERSATILE INTERMEDIATES IN HETEROCYCLIC SYNTHESIS
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Methods for the preparation of 6H-1,3-oxazin-6-ones are reviewed and details of a new, efficient synthesis of the title compounds starting from tert-butyl 3-acylaminoacrylates are presented.A comprehensive table of alkyl- and aryl-substituted 1,3-oxazin-6-ones prepared by the old and new routes has been compiled.The (4+2)-cycloaddition reactions of 1,3-oxazin-6-ones with a variety of dienophiles leads to pyridines, 4-(dialkylamino)pyridines, 4-alkoxypyridines, 4H-azepines and 4H-diazepines after extrusion of CO2 from the initial products of the cycloaddition reaction.These reactions proceed in most cases with complete regioselectivity.Oxazinones in which the 2-azadiene moiety is markedly electron deficient react with pyrroles and indoles to produce dihydrooxazinones which can be further transformed to pyrroloimidazoles and indoloimidazoles, respectively.Treatment of the title compounds with ammonia affords pyrimidin-6-ones whereas with other nucleophiles, e.g. water, alcohols and amines, ring-opened products are obtained.Irradiation of 1,3-oxazin-6-ones at low temperature produces 2-oxa-6-azabicyclohex-5-en-3-ones whereas at room temperature in the presence of sensitizers, dimerization takes place.
- Steglich, Wolfgang,Jeschke, Rainer,Buschmann, Ernst
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p. 361 - 372
(2007/10/02)
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- The Mechanism of Trifluoroacetylation of Indoles
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The mechanism of the reaction between substituted indoles and trifluoroacetic anhydride has been studied by product identification and n.m.r. spectroscopy.Experimental evidence is given for the stability of an ion pair intermediate.
- Cipiciani, Antonio,Clementi, Sergio,Giulietti, Gianfranco,Marino, Gianlorenzo,Savelli, Gianfranco,Linda, Paolo
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p. 523 - 530
(2007/10/02)
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- REACTION OF INDOLES WITH TRIFLUORACETIC ACID
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3-Trifluoracetyl indoles are formed by the action of trifluoracetic acid on indole-2-carboxylic acid and its benzo-substituted derivatives.When unsubstituted indole is refluxed with trifluoracetic acid, it gives 3-triflouracetylindole in 30percent yield.
- Kost, A. N.,Budylin, V. A.,Romanova, N. N.,Matveeva, E. D.
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p. 921 - 923
(2007/10/02)
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- SYNTHESIS OF AROMATIC ALDEHYDES VIA 2-ARYL-N,N'-DIACYL-4-IMIDAZOLINES
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Diacylimidazolium ions yield adducts with aromatic compounds.Thus the N,N'-diacetylimidazolium ion and indole gives 1,3-diacetyl-2-(3-indolyl)-4-imidazoline.Less reactive substrates such as thiophene, anisole and 1,3-dimethylbenzene fail to react with this reagent but do form adducts (e.g. 1,3-bis-(trifluoroacetyl)-2-(2-thienyl)-4-imidazoline) with an imidazole/trifluoroacetic anhydride reagent.All of the adducts could be converted to the corresponding aldehyde under mild conditions.The synthetic scope of the new synthesis is similar to that of the Vilsmeier-Haack reaction.
- Bergman, Jan,Renstroem, Lars,Sjoeberg, Birger
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p. 2505 - 2512
(2007/10/02)
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