- Fusarochromene, a novel tryptophan-derived metabolite from: Fusarium sacchari
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Fusarochromene isolated from the plant pathogenic fungus, Fusarium sacchari is closely related to a group of mycotoxins including fusarochromanone previously isolated from various Fusaria spp. Despite their assumed polyketide biogenesis, incorporation studies with 13C-labelled acetate, glycerol and tryptophans show that fusarochromene is unexpectedly derived via oxidative cleavage of the aromatic amino acid tryptophan. A putative biosynthetic gene cluster has been identified. This journal is
- Marshall, James W.,De Mattos-Shipley, Kate M. J.,Ghannam, Iman A. Y.,Munawar, Asifa,Killen, Jonathan C.,Lazarus, Colin M.,Cox, Russell J.,Willis, Christine L.,Simpson, Thomas J.
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- NOVEL COMPOUND AND COMPOSITION FOR PREVENTION OR TREATMENT OF RESPIRATORY DISEASES COMPRISING SAME AS ACTIVE INGREDIENT
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The present invention relates to a novel compound, and a composition for preventing or treating of respiratory disease comprising the novel compound, E- or Z-isomer thereof, optical isomer thereof, a mixture of two isomers thereof, precursor thereof, pharmaceutically acceptable salt thereof or solvate thereof as an active ingredient.
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- Potent Inhibition of Nicotinamide N-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics
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Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-l-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.
- Buijs, Ned,Campagna, Roberto,Emanuelli, Monica,Gao, Yongzhi,Innocenti, Paolo,Jespers, Willem,Martin, Nathaniel I.,Parsons, Richard B.,Sartini, Davide,Van Haren, Matthijs J.,Van Westen, Gerard J. P.,Zhang, Yurui,Gutiérrez-De-Terán, Hugo
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p. 12938 - 12963
(2021/09/11)
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- Recyclable and reusablen-Bu4NBF4/PEG-400/H2O system for electrochemical C-3 formylation of indoles with Me3N as a carbonyl source
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A safe, practical and eco-friendly electrochemical methodology for the synthesis of 3-formylated indoles has been developed by the utilization of Me3N as a novel formylating reagent. Stoichiometric oxidants, metal catalysts, and activating agents were avoided in this method, and an aqueous biphasic system ofn-Bu4NBF4/PEG-400/H2O was used as a recyclable and reusable reaction medium, which made this electrosynthesis approach more sustainable and environmentally friendly. This process expanded the substrate scope and functional group tolerance for bothN-EDG andN-EWG indoles. Furthermore, late-stage functionalization and total/formal synthesis of drugs and natural products were realized by means of this route.
- Cheng, Didi,Li, Jingyi,Li, Yujin,Ling, Fei,Liu, Lei,Liu, Tao,Zhong, Weihui
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supporting information
p. 4107 - 4113
(2021/06/17)
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- 4CzIPN catalyzed photochemical oxidation of benzylic alcohols
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A green photoredox oxidation of benzylic primary and secondary alcohols to aldehydes and ketones with air as an oxidant was reported. The oxidation shows broad substrate scope and excellent selectivity over benzylic alcohols to the aliphatic alcohols. Further mechanistic studies revealed a quinuclidine mediated HAT process, and blue LEDs promoted 4CzlPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene) photoredox cycle were involved in our oxidation.
- Zhang, Heng,Guo, Tianyun,Wu, Mingzhong,Huo, Xing,Tang, Shouchu,Wang, Xiaolei,Liu, Jian
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supporting information
(2021/02/20)
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- Synthesis and Biological Evaluation of Hapten-Clicked Analogues of The Antigenic Peptide Melan-A/MART-126(27L)-35
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A click-chemistry-based approach was implemented to prepare peptidomimetics designed in silico and made from aromatic azides and a propargylated GIGI-mimicking platform derived from the altered Melan-A/MART-126(27L)-35 antigenic peptide ELAGIGILTV. The CuI-catalyzed Huisgen cycloaddition was carried out on solid support to generate rapidly a first series of peptidomimetics, which were evaluated for their capacity to dock at the interface between the major histocompatibility complex class-I (MHC-I) human leucocyte antigen (HLA)-A2 and T-cell receptors (TCRs). Despite being a weak HLA-A2 ligand, one of these 11 first synthetic compounds bearing a p-nitrobenzyl-triazole side chain was recognized by the receptor proteins of Melan-A/MART-1-specific T-cells. After modification of the N and C termini of this agonist, which was intended to enhance HLA-A2 binding, one of the resulting seven additional compounds triggered significant T-cell responses. Thus, these results highlight the capacity of naturally circulating human TCRs that are specific for the native Melan-A/MART-126-35 peptide to cross-react with peptidomimetics bearing organic motifs structurally different from the native central amino acids.
- Tarbe, Marion,Miles, John J.,Edwards, Emily S. J.,Miles, Kim M.,Sewell, Andrew K.,Baker, Brian M.,Quideau, Stéphane
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supporting information
p. 799 - 807
(2020/04/20)
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- Synthesis of Antitricyclic Morpholine Derivatives through Iodine(III)-Mediated Intramolecular Umpolung Cycloaddition of Olefins
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A (diacetoxyiodo)benzene-mediated intramolecular cycloaddition of olefins to construct tricyclic morpholines is presented. A series of substituted tricyclic morpholines were obtained in one-step simple operation under mild conditions, and the NMR studies
- Deng, Qingfu,Feng, Yangyang,Xiong, Ruimei,Xiong, Yan,Yang, Chenglin,Zhang, Xiaohui
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p. 4500 - 4506
(2020/04/09)
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- Imidazopyridine-fused [1,3]diazepinones: modulations of positions 2 to 4 and their impacts on the anti-melanoma activity
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A series of 19 novel pyrido-imidazodiazepinones, with modulations of positions 2, 3 and 4 of the diazepine ring were synthesised and screened for their in vitro cytotoxic activities against two melanoma cell lines (A375 and MDA-MB-435) and for their poten
- Ali, Lamiaa M. A.,Baccon-Sollier, Paul Le,Cuq, Pierre,Lichon, Laure,Malki, Yohan,Masurier, Nicolas,Maye, Morgane,Vincent, Laure-Ana?s
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p. 935 - 949
(2020/04/17)
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- Asymmetric Total Synthesis of Vincadifformine Enabled by a Thiourea-Phosphonium Salt Catalyzed Mannich-Type Reaction
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An asymmetric total synthesis of vincadifformine is described. The limited tactics with chiral cation-directed catalysis in total synthesis inspired the development of our strategy for accessing this alkaloid in enantionrich form. The route features a thiourea–phosphonium salt catalyzed Mannich-type reaction, a phosphine-promoted aza-Morita–Baylis–Hillman reaction and a trifluoroacetic acid promoted deprotection/amidation cascade process.
- Pan, Lu,Zheng, Chang-Wu,Fang, Guo-Sheng,Hong, Hao-Ran,Liu, Jun,Yu, Long-Hui,Zhao, Gang
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supporting information
p. 6306 - 6310
(2019/04/26)
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- Solvent-dependent regio- and stereo-selective reactions of 3-formylchromones with 2-aminobenzothiazoles and transacetalization efficiency of the product 3-((benzo[: D] thiazol-2-ylimino)butyl)-4 H -chromen-4-one
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Using 2-propanol as the solvent, 3-formylchromones and 2-aminobenzothiaoles formed corresponding imines, while 1° and 2°-alcohols formed the corresponding 2-alkoxy-3-enamines with selectivity for the Z-isomer. Changing the substrates with similar molecules such as 3-formylchromone with quinoline-, quinolone- and indole-3-carbaldehydes sometimes resulted in the formation of the corresponding imines, whereas replacing 2-aminobenzothiazole with amides resulted in the formation of acetals. Considering the effect of the solvent, replacing alcohols with the aprotic solvents THF and CH2Cl2 resulted in the formation of imines and enamines, which are the characteristic reactions of 2-propanol and other 1° and 2°-alcohols, respectively. 2-Alkoxy-3-enamines were found to undergo transacetalization with both short and long chain alcohols. The novelty of these reactions is that they did not require an external catalyst, all the reactions were performed at the same temperature, and purification was achieved by filtration. The transacetalization we performed herein is a new concept, which has not been reported to date. In contrast, other similar reactions, such as transalkoxylation, transalkylation, and transetherification, are performed on a commercial scale using expensive catalysts such as Otera's catalyst. The highly sensitive nature of 3-formylchromones towards variations in the substrates and solvents to form different products and the reason behind the selective formation of the Z-isomer of 2-alkoxy-3-enamines and its transacetalization efficiency need further studies to understand the reaction mechanism and possibly other factors such as solvent effects.
- Ahmed, Owais,Cherkadu, Vandana,Kalavagunta, Praveen Kumar,Shang, Jing
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p. 20573 - 20581
(2019/07/12)
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- Sensitive Assays by Nucleophile-Induced Rearrangement of Photoactivated Diarylethenes
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Upon light-induced isomerization, diarylethenes (DAEs) equipped with reactive aldehyde moieties rearrange selectively in the presence of amines, accompanied by decoloration. In a comprehensive study, the probe structure was optimized with regard to its inherent reactivity in the nucleophile-triggered rearrangement reaction. Detailed structure-reactivity relationships could be derived, in particular with regard to the type of integrated (het)aryl moieties as well as the location of the formyl residue, and the probes' intrinsic reactivity with primary and secondary amines was optimized. Utilizing an ancillary base, the initially formed rearrangement product can engage in a subsequent catalytic cycle, leading to an amplified decoloration process. This additional catalytic pathway allows us to enhance the sensitivity of our method and successfully discriminate between amines and thiols. Moreover, probes that exhibit strong analyte-induced fluorescence modulation have been designed to further decrease the detection limit by using a more sensitive read-out. The optimized DAE probes are promising molecular components for future programmable sensing materials and devices.
- Fredrich, Sebastian,Bonasera, Aurelio,Valderrey, Virginia,Hecht, Stefan
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supporting information
p. 6432 - 6440
(2018/05/31)
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- With anti-tumor activity of the compound and its preparation method and in pharmacy (by machine translation)
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The invention belongs to the field of pharmaceutical chemistry synthesis, relates to has prominent anti-tumor activity comprises two aryl hydantoin compound and β - lactam compound and its application in pharmacy. This invention also includes the compound
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Paragraph 0217; 0218-0220
(2018/11/03)
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- Zincation and Magnesiation of Functionalized Silylated Cyanohydrins Using TMP-Bases
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Polyfunctional silylated cyanohydrins are readily magnesiated or zincated with TMPMgCl·LiCl or TMP 2 Zn·2MgCl 2 ·2LiCl leading to the corresponding metallated derivatives. These Mg- or Zn-derivatives react with various electrophiles such as benzylic bromides, allylic bromides, acid chlorides, aldehydes, NCCO 2 Et, or MeSO 2 SMe. Subsequently, TBAF-deprotection provides the corresponding keto or 1,2-diketo derivatives.
- Castelló-Micó, Alicia,Knochel, Paul
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p. 155 - 169
(2017/10/07)
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- Structure-Enabled Discovery of a Stapled Peptide Inhibitor to Target the Oncogenic Transcriptional Repressor TLE1
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TLE1 is an oncogenic transcriptional co-repressor that exerts its repressive effects through binding of transcription factors. Inhibition of this protein–protein interaction represents a putative cancer target, but no small-molecule inhibitors have been published for this challenging interface. Herein, the structure-enabled design and synthesis of a constrained peptide inhibitor of TLE1 is reported. The design features the introduction of a four-carbon-atom linker into the peptide epitope found in many TLE1 binding partners. A concise synthetic route to a proof-of-concept peptide, cycFWRPW, has been developed. Biophysical testing by isothermal titration calorimetry and thermal shift assays showed that, although the constrained peptide bound potently, it had an approximately five-fold higher Kd than that of the unconstrained peptide. The co-crystal structure suggested that the reduced affinity was likely to be due to a small shift of one side chain, relative to the otherwise well-conserved conformation of the acyclic peptide. This work describes a constrained peptide inhibitor that may serve as the basis for improved inhibitors.
- McGrath, Sally,Tortorici, Marcello,Drouin, Ludovic,Solanki, Savade,Vidler, Lewis,Westwood, Isaac,Gimeson, Peter,Van Montfort, Rob,Hoelder, Swen
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p. 9577 - 9584
(2017/07/22)
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- Efficient and expeditious chemoselective BOC protection of amines in catalyst and solvent-free media
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A green and eco-friendly route for the almost quantitative BOC protection of a large variety of aliphatic and aromatic amines, amino acids, and amino alcohols is reported in catalyst and solvent-free media under mild reaction conditions. The products were confirmed by 1H, 13C NMR, IR spectroscopy, and in some cases, elemental analysis. This protocol does not require any water quenches, solvent separations, and purification steps, such as recrystallization and column chromatography.
- Viswanadham, Balaga,Mahomed, Abdul S.,Friedrich, Holger B.,Singh, Sooboo
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p. 1355 - 1363
(2017/02/15)
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- A Modular Formal Total Synthesis of (±)-Cycloclavine
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Cycloclavine is a clavine-type Ergot alkaloid noteworthy for its unique pentacyclic skeleton featuring a 3-azabicyclo[3.1.0]hexane substructure. A short convergent route to the racemic alkaloid is described which comprises only eight linear steps and requires only four chromatographic purifications. The two key building blocks can be prepared in high yield from commercially available starting materials. Two consecutive coupling reactions, namely a selective alkylation of a dienolate and a Heck reaction, are the key steps of the reaction sequence. (Chemical Equation Presented).
- Netz, Natalie,Opatz, Till
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p. 1723 - 1730
(2016/03/01)
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- Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents
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Secretory phospholipase A2 (sPLA2) is an important enzyme that plays a key role in various inflammatory diseases including cancer and its inhibitors have been developed as preventive or therapeutic agents. In the present study, a series of new indole containing isoxazole derivatives (10a–10o) is synthesized and evaluated for their sPLA2 inhibitory activities. All compounds (10a–10o) showed significant sPLA2 inhibition activities both in vitro and in vivo studies which is substantiated in in silico studies. Among all the tested compounds, 10o showed potent sPLA2 inhibition activity, that is comparable or more to ursolic acid (positive control). Further studies demonstrated that 10o showed in vitro antiproliferative activity when tested against MCF-7 breast and DU145 prostate cancer cells. Furthermore, compounds 10a–10o obeyed lipinsky's rule of 5 and suggesting druggable properties. The in vitro, in vivo and in silico results are encouraging and warrant pre-clinical studies to develop sPLA2-inhibitory compound 10o as novel therapeutic agent for various inflammatory disorders and several malignancies.
- Pedada, Srinivasa Rao,Yarla, Nagendra Sastry,Tambade, Pawan J.,Dhananjaya, Bhadrapura Lakkappa,Bishayee, Anupam,Arunasree, Kalle M.,Philip, Gundala Harold,Dharmapuri, Gangappa,Aliev, Gjumrach,Putta, Swathi,Rangaiah, Gururaja
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p. 289 - 297
(2018/04/19)
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- Concise synthesis of (2R,4R)-monatin
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Monatin, 4-hydroxy-4-(3-indolylmethyl)-glutamic acid, is a naturally occurring sweet amino acid. The (2R,4R)-monatin isomer has been found to be the sweetest among its four stereoisomers. A concise and efficient synthesis of (2R,4R)-monatin was accomplished by the alkylation of (4R)-N-tert-butoxycarbonyl (tBoc)-4-tert-butyldimethylsilyoxy-D-pyroglutamic acid methyl ester with tert-butyl 3-(bromomethyl)-1H-indole-1-carboxylate to give (4R)-N-tBoc-4-tert-butyldimethylsilyloxy-4-(N-tBoc-3-indolylmethyl)-D-pyroglutamic acid methyl ester, i.e., the lactam form of (2R,4R)-monatin with protecting groups. This was followed by the hydrolysis of the lactam ring and deprotection. The 4-hydroxyl D-pyroglutamic acid derivative was demonstrated to be a suitable precursor for the efficient preparation of (2R,4R)-monatin in high optical purity because the alkylation proceeded in regioselective and stereoselective manners at C4 to form appropriate asymmetric tetra-substituted carbon center; the resulting alkylated pyroglutamic acid derivative was then easily converted into the linear form of monatin.
- Amino, Yusuke
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p. 1242 - 1247
(2016/08/11)
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- A Mild TEMPO-Catalyzed Aerobic Oxidative Conversion of Aldehydes into Nitriles
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An efficient method to prepare nitriles from aldehydes using hexamethyldisilazane (HMDS) as the nitrogen source has been developed. The reactions were performed with 2,2,6,6-tetramethylpiperidine l-oxyl (TEMPO) as the catalyst, NaNO2 or TBN as the co-catalyst, and molecular oxygen as the terminal oxidant under mild conditions. A variety of aromatic, heteroaromatic, aliphatic and allylic aldehydes could be converted into their corresponding nitriles in good to excellent yields.
- Fang, Chaojie,Li, Meichao,Hu, Xinquan,Mo, Weimin,Hu, Baoxiang,Sun, Nan,Jin, Liqun,Shen, Zhenlu
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supporting information
p. 1157 - 1163
(2016/04/19)
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- Cobalt-Catalyzed Enantioselective Directed C-H Alkylation of Indole with Styrenes
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A cobalt-chiral phosphoramidite catalyst promotes enantioselective imine-directed C2-alkylation of Boc-protected indoles with styrenes. The reaction affords 1,1-diarylethane products in moderate to good yields with good enantioselectivities under mild conditions. A deuterium-labeling experiment suggests that the enantioselectivity is controlled by both the styrene insertion and the C-C reductive elimination steps. (Chemical Equation Presented).
- Lee, Pin-Sheng,Yoshikai, Naohiko
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supporting information
p. 22 - 25
(2015/07/28)
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- Dipeptide analogs for treating conditions associated with amyloid fibril formation
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Dipeptide analogs comprising a tryptophan (Trp) moiety coupled to a beta-sheet breaker moiety derived from alpha-aminoisobutyric acid (Aib) are disclosed. The dipeptide analogs exhibit an improved performance in inhibiting amyloid fibril formation, as compared to previously described dipeptides. Compositions containing the dipeptide analogs and uses thereof in treating amyloid-associated diseases and disorders are also disclosed.
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Page/Page column 35; 36
(2015/09/22)
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- INDOLE-3-CARBINOL DERIVATIVES
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The present invention relates to novel stable indole-3-carbinol derivatives of Formula-I and its pharmaceutical composition and biological activity. The present invention includes compositions and methods for the treatment and prevention of conditions ass
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Page/Page column 18
(2015/02/02)
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- Aerobic transition-metal-free visible-light photoredox indole C-3 formylation reaction
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An aerobic visible-light-promoted indole C-3 formylation reaction catalyzed by Rose Bengal has been developed. This transition-metal-free process employs molecular oxygen as the terminal oxidant and uses TMEDA as the one-carbon source through C-N bond cleavage. The reaction is compatible with a variety of functional groups.
- Li, Xiang,Gu, Xiangyong,Li, Yongjuan,Li, Pixu
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p. 1897 - 1900
(2014/06/24)
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- One-pot transformation of methylarenes into aromatic aldehydes under metal-free conditions
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On the basis of studies of the transformation of benzylic bromides into the corresponding aromatic aldehydes by treatment with N-methylmorpholine N-oxide, various methylarenes were treated either with DBDMH in the presence of AIBN in acetonitrile at reflux (Method A) or with NBS in CCl4 under irradiation with a tungsten lamp at 30 °C (Method B), followed by treatment with N-methylmorpholine N-oxide to provide aromatic aldehydes in good yields. These methods could be adopted in one-pot transformations of methylarenes into aromatic aldehydes under conditions free of less toxic reagents and transition metals. Copyright
- Tabata, Masayuki,Moriyama, Katsuhiko,Togo, Hideo
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p. 3402 - 3410
(2014/06/09)
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- 4-(Dimethylamino)pyridine as a catalyst for the lactonization of 4-hydroxy-2-methylenebutanoate esters
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The catalytic action of 4-(dimethylamino)pyridine (DMAP) in lactonizing 4-hydroxy-2-methylenebutanoate esters to 2-methylene-γ-butyrolactones is described. The use of DMAP, which functions as an excellent complement to the more traditional acid-catalyzed lactonization protocol, allows for the synthesis of 2-methylene-γ-butyrolactones containing acid-sensitive groups under essentially neutral conditions.
- Nicponski, Daniel R.
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supporting information
p. 2075 - 2077
(2014/04/03)
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- Light- and redox-gated molecular brakes consisting of a pentiptycene rotor and an indole pad
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Two photochemically and electrochemically active alkenes 3Me and 3An containing pentiptycene and indole groups have been synthesized and investigated as light and/or redox-gated molecular brakes. The pentiptycene group functions as the four-bladed rotor, the indole group as the brake pad, and the vinylene group as the switch module. The E configuration corresponds to the brake-off state, in which the rotation of the rotor is free with a rotation rate of 108-109 at ambient temperature according to DFT calculations. The Z configuration corresponds to the brake-on state, in which the rotation rate is decreased to 101-102, depending on the N-substituent of indole, according to line-shape analysis of variable temperature 13C NMR spectra. The overall braking effect reaches a factor of 106-108. While the combined photochemical E → Z and electrochemical Z → E switching has a higher capacity than the two-way photochemical switching in the case of 3Me, the switching capacity are comparable for the two methods in 3An. The results also show that photochemical E-Z isomerization is much more reliable than the electrochemical counterpart, as the stability of the redox intermediates plays a critical role in determining the robustness of the molecular brakes via electrochemical switching. The photochemical and/or electrochemical switching between the E and Z isomers of two alkenes substituted with both pentiptycene and indole groups results in a change of the rotation rate as large as 106-108 fold for the pentiptycene group about the pentiptycene-vinylene C-C bond, corresponding to a new generation of light- and redox-gated molecular brakes.
- Kao, Chen-Yi,Lee, I-Tsun,Prabhakar, Ch.,Yang, Jye-Shane
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p. 507 - 516
(2014/05/20)
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- Congested C-C bonds by Pd-catalyzed enantioselective allyl-allyl cross-coupling, a mechanism-guided solution
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Under the influence of a chiral bidentate diphosphine ligand, the Pd-catalyzed asymmetric cross-coupling of allylboron reagents and allylic electrophiles establishes 1,5-dienes with adjacent stereocenters in high regio-and stereoselectivity. A mechanistic study of the coupling utilizing reaction calorimetry and density functional theory analysis suggests that the reaction operates through an inner-sphere 3,3′-reductive elimination pathway, which is both rate-defining and stereodefining. Coupled with optimized reaction conditions, this mechanistic detail is used to expand the scope of allyl-allyl couplings to allow the generation of 1,5-dienes with tertiary centers adjacent to quaternary centers as well as a unique set of cyclic structures.
- Ardolino, Michael J.,Morken, James P.
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supporting information
p. 7092 - 7100
(2014/06/09)
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- Microwave-assisted synthesis of 3,5-disubstituted isoxazoles and evaluation of their anti-ageing activity
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One-pot uncatalysed microwave-assisted 1,3-dipolar cycloaddition reactions between in situ generated nitrile oxides and alkynes bearing protected antioxidant substituents, were regioselectively afforded 3,5-disubstituted isoxazoles. The yields were modera
- Koufaki, Maria,Fotopoulou, Theano,Kapetanou, Marianna,Heropoulos, Georgios A.,Gonos, Efstathios S.,Chondrogianni, Niki
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supporting information
p. 508 - 515
(2014/07/21)
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- HETEROCYCLIC COMPOUNDS AS INHIBITORS OF LEUKOTRIENE PRODUCTION
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The present invention relates to compound of formula (I): or pharmaceutically acceptable salts thereof, wherein R1-R7, A and HET are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes
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-
Paragraph 0224; 0225
(2013/08/14)
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- Aerobic oxidation of indole carbinols using Fe(NO3) 3·9H2O/TEMPO/NaCl as catalysts
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A practical aerobic oxidation of indole carbinols using Fe(NO 3)3·9H2O/TEMPO/NaCl in DCE at room temperature and atmospheric pressure of oxygen affording aldehydes or ketones in good to excellent yields was developed. Furthermore, when using the industrially favored solvent toluene instead of DCE and air instead of pure oxygen, this protocol also works smoothly, demonstrating its high potential for possible industrial application.
- Liu, Jinxian,Ma, Shengming
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p. 4186 - 4193
(2013/07/19)
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- Highly efficient Cu(I)-catalyzed oxidation of alcohols to ketones and aldehydes with diaziridinone
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A novel and efficient Cu(I)-catalyzed oxidation of alcohols has been achieved with di-tert-butyldiaziridinone as the oxidant under mild conditions. A wide variety of primary and secondary alcohols with various functional groups can be oxidized to aldehydes and ketones in high yields. The reaction proceeds under neutral conditions making it compatible with acid- or base-sensitive substrates, and it is amenable to gram scale.
- Zhu, Yingguang,Zhao, Baoguo,Shi, Yian
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supporting information
p. 992 - 995
(2013/04/10)
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- Stereocontrol in palladium-catalyzed propargylic substitutions: Kinetic resolution to give enantioenriched 1,5-enynes and propargyl acetates
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Kinetic resolution during the catalytic allyl-propargyl cross-coupling with chiral starting materials can be accomplished with a chiral palladium catalyst. These reactions offer ready access to enantiomerically enriched enyne products from simple, readily
- Ardolino, Michael J.,Eno, Meredith S.,Morken, James P.
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p. 3413 - 3419
(2013/12/04)
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- PHENYL-UREA AND PHENYL-CARBAMATE DERIVATIVES AS INHIBITORS OF PROTEIN AGGREGATION
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The present invention relates to certain phenyl-urea and phenyl-carbamate derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, and multiple system atrophy.
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Paragraph 0081; 0082
(2013/10/21)
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- A new route to α-carbolines based on 6π-electrocyclization of indole-3-alkenyl oximes
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Indoles are converted into α-carbolines in four steps by acylation at C-3, Boc-protection, olefination of the resulting 3-indolyl aldehydes or ketones to give N-Boc-3-indolyl alkenyl oxime O-methyl ethers, which upon heating to 240 C under microwave irradiation undergo loss of the Boc-group, and 6π-electrocyclization to α-carbolines, following aromatization by loss of methanol (11 examples, 30-90% yield).
- Markey, Sophie J.,Lewis, William,Moody, Christopher J.
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supporting information
p. 6306 - 6308
(2014/01/17)
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- VIRAL REPLICATION INHIBITORS
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The present invention relates to a series of novel compounds, methods to prevent or treat viral infections in animals by using the novel compounds and to said novel compounds for use as a medicine, more preferably for use as a medicine to treat or prevent viral infections, particularly infections with RNA viruses, more particularly infections with viruses belonging to the family of the Flaviviridae, and yet more particularly infections with the Dengue virus. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of viral infections. The invention also relates to processes for preparation of the compounds.
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Page/Page column 129; 138
(2013/04/13)
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- Intramolecular Pd(0)-catalyzed reactions of (2-iodoanilino)-aldehydes: A joint experimental-computational study
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An extensive joint experimental-computational density functional theory (DFT) study has been carried out to gain insight into the factors that control the chemoselectivity (i.e., acylation vs α-arylation reaction) of palladium-catalyzed cyclizations of (2-iodoanilino)-aldehydes. To this end, the nature of the tethers joining the aniline nitrogen and the aldehyde moiety, different palladium precatalysts and reaction conditions (base and temperature), as well as different additives (mono- and bidendate ligands) has been explored. The adequate selection of these variables allows for the control of the selectivity of the process. Thus, (2-iodoanilino)-aldehydes generally lead to the formation of nucleophilic addition derived products when Cs 2CO3/Et3N is used as base. In contrast, the use of stronger bases like KtOBu (in the presence of PhOH) mainly forms α-arylation reaction products. The different reaction pathways leading to the experimentally observed reaction products have been studied by means of computational tools.
- Sole, Daniel,Mariani, Francesco,Fernandez, Israel,Sierra, Miguel A.
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p. 10272 - 10284
(2013/01/15)
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- Synthesis and biological activities of 4-substituted pyrrolo[2,3-a] carbazole Pim kinase inhibitors
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Pyrrolo[2,3-a]carbazole-3-carbaldehydes are potent Pim kinase inhibitors with in vitro antiproliferative activities. In the present study, we report the synthesis and biological activities (Pim kinase inhibition and in vitro antiproliferative potency) of
- Giraud, Francis,Akué-Gédu, Rufine,Nauton, Lionel,Candelon, Nicolas,Debiton, Eric,Théry, Vincent,Anizon, Fabrice,Moreau, Pascale
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p. 225 - 236
(2013/01/15)
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- Construction of 1,5-enynes by stereospecific Pd-catalyzed allyl-propargyl cross-couplings
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The palladium-catalyzed cross-coupling of chiral propargyl acetates and allyl boronates delivers chiral 1,5-enynes with excellent levels of chirality transfer and can be applied across a broad range of substrates.
- Ardolino, Michael J.,Morken, James P.
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supporting information; scheme or table
p. 8770 - 8773
(2012/07/02)
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- Indolyl-Substituted Pyrazino-Quinolines and Their Use for the Treatment of Cancer
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There is provided compounds of formula I, wherein the wedged bonds, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, Rsu
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Page/Page column 12-14
(2012/06/30)
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- Synthesis of C-1 indol-3-yl substituted tetrahydroisoquinoline derivatives via a Pictet-Spengler approach
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A protocol for the diastereoselective synthesis of C-1 indol-3-yl substituted tetrahydroisoquinoline derivatives via Pictet-Spengler condensation with L-DOPA or l-DOPA derivatives and 1H-indole-3-carbaldehydes is presented. The protocol is used for the successful synthesis of several tetrahydroisoquinolines as well as diketopiperazine fused analogues.
- Larsson, Rikard,Blanco, Narda,Johansson, Martin,Sterner, Olov
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supporting information
p. 4966 - 4970
(2012/11/07)
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- Synthesis and in vitro antifungal evaluation of 2-(2,4-difluorophenyl)-1- [(1H-indol-3-ylmethyl)methylamino]-3-(1H-1,2,4-triazol-1-yl)propan-2-ols
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We extended our previous studies based on the design of 1-[(1H-indol-5-ylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents toward the identification of new indol-3-ylmethylamino derivatives. The majority of these compounds exhibited antifungal activity against a Candida albicans strain (minimum inhibitory concentrations ranging from 199.0 to 381.0ng/mL) suggesting an inhibition of 14α-demethylase by sterol analysis studies, but are weaker inhibitors compared to their indol-5-ylmethylamino analogs.
- Guillon, Remi,Loge, Cedric,Pagniez, Fabrice,Ferchaud-Roucher, Veronique,Duflos, Muriel,Picot, Carine,Pape, Patrice Le
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p. 261 - 269
(2011/11/06)
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- Decarboxylative Claisen rearrangement reactions: Synthesis and reactivity of alkylidene-substituted indolines
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Microwave-assisted decarboxylative Claisen rearrangement (dCr) reactions of substituted acetate derivatives of 3-(hydroxyalkyl)indoles give de-aromatised products. The reactivity of the resultant compounds was evaluated.
- Camp, Jason E.,Craig, Donald,Funai, Kiyohiko,White, Andrew J. P.
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experimental part
p. 7904 - 7912
(2011/12/05)
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- PEG-mediated facile protocol for N-Boc protection of amines
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We have reported an efficient and eco-friendly protocol for the protection of various structurally and electronically divergent aryl and aliphatic amines using (Boc)2O in the presence of PEG-400 at room temperature. The reaction gave excellent
- Siddaiah,Basha,Padma Rao,Viplava Prasad,Suryachendra Rao
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experimental part
p. 1127 - 1129
(2011/02/28)
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- Asymmetric synthesis of proline-based conformationally constrained tryptophan mimetic
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The synthesis of an optically pure proline-based tryptophan mimetic is described. The strategy involves the in situ generation of an unprecedented allylmetal species containing the indole moiety, and its coupling with a chiral imine. The construction of the 3-substitued proline skeleton is then achieved through a hydrozirconation/iodination sequence applied to the resulting homoallylic amine.
- Delaye, Pierre-Olivier,Vasse, Jean-Luc,Szymoniak, Jan
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supporting information; experimental part
p. 3635 - 3637
(2010/09/06)
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- 3-O and 2-C Alkylation of L-ascorbates with benzyl halides and N-substituted indolemethanol derivatives
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Coupling of alkali metal ascorbates with benzyl halides and 2and 3-hydroxymethylindole methanesulfonates resulted in L-ascorbic acid 3-Oand 2-C-derivatives. In contrast to 3-Obenzyl L-ascorbate, its indole analogs are unstable compounds, which underwent decomposition or rearrangement during isolation to give thermodynamically stable 2-C-isomers.
- Korolev,Luzikov,Reznikova,Preobrazhenskaya
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experimental part
p. 457 - 462
(2011/02/17)
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- N-alkylated oligoamide α-helical proteomimetics
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Generic approaches for the design and synthesis of small molecule inhibitors of protein-protein interactions (PPIs) represent a key objective in modern chemical biology. Within this context, the α-helix mediated PPIs have received considerable attention as targets for inhibition using small molecules, foldamers and proteomimetics. This manuscript describes a novel N-alkylated aromatic oligoamide proteomimetic scaffold and its solid-phase synthesis - the first time such an approach has been used for proteomimetics. The utility of these scaffolds as proteomimetics is exemplified through the identification of potent μM inhibitors of the p53-hDM2 helix mediated PPI - a key oncogenic target.
- Campbell, Frederick,Plante, Jeffrey P.,Edwards, Thomas A.,Warriner, Stuart L.,Wilson, Andrew J.
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supporting information; experimental part
p. 2344 - 2351
(2010/07/08)
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- NEW COMPOUNDS AND MEDICAL USE
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There is provided compounds of formula (I), wherein the wedged bonds, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R
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Page/Page column 31-32
(2011/01/12)
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- INDOLYL-SUBSTITUTED PYRAZINO-QUINOLINES AND THEIR USE FOR THE TREATMENT OF CANCER
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There is provided compounds of formula I, wherein the wedged bonds, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, Rsu
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Page/Page column 39
(2011/01/12)
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- Efficient N-tert-butoxycarbonylation of indoles with di-tert-butyl dicarbonate catalyzed by cesium fluoride
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An environmentally friendly process for the tert-butoxycarbonylation of indoles with di-tert-butyl dicarbonate has been developed. Catalytic amount of cesium fluoride can accelerate this tert-butoxycarbonylation. Georg Thieme Verlag Stuttgart.
- Inahashi, Nobuyuki,Matsumiya, Ayako,Sato, Tsuneo
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p. 294 - 296
(2008/12/21)
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