- Development of Novel Imaging Fluorescent Agents Bearing Anti-Inflammatory Drugs: Synthesis, Structural Characterization and Evaluation of Biological Activity
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Abstract: A new series of 5,6-benzocoumarin derivatives carrying anti-inflammatory drugs were synthesized via alkylamide spacers, the target to develop novel imaging fluorescent agents as useful technique to cancer early discovery. Experimentally, treatment of N-Boc-1,3-propanediamine with ethyl 5,6-benzocoumarin-3-carboxlate (III) under reflux conditions followed by hydrolyzed with CF3COOH to the corresponding primary amine (V), then treatment of derivative (V) with anti-inflammatory drugs have carboxylic group in presence of DCC (N,N'-dicyclohexylcarbodiimide) as catalyst and MeCN as solvent. The structure of the synthesized compounds was confirmed by FT-IR, NMR (1H,13C) spectral data as well as elemental analysis. The fluorescence properties study was investigated spectrophotometrically in methanol and maximum emission (λem) exhibited within range 411–436 nm, meanwhile, the quantum yields were calculated comparison to Rhodamine 6G as reference. Interestingly, the compound (III) gave a higher quantum yield (ΦF = 0.96), meanwhile, compounds (VII, VIII, IX and XI) gave reasonable quantum yields (ΦF) 0.60, 0.65, 0.78 and 0.84, respectively. All synthesized compounds were screened for their anti-AChE and antimicrobial activity. Based on the results, some of the compounds showed good activity in compared to the standard drugs.
- Adnan, Shaimaa,Jaber, Qassim A. H.,Nabeel, A. Abdul-Rida
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Read Online
- A coumarin embedded highly sensitive nitric oxide fluorescent sensor: Kinetic assay and bio-imaging applications
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Fluorescence spectroscopy is a significant bio-analytical technique for specific detection of nitric oxide (NO) and for broadcasting the in vitro and in vivo biological activities of this gasotransmitter. Herein, a benzo-coumarin embedded smart molecular probe (BCM) is employed for NO sensing through detailed fluorescence studies in purely aqueous medium. All the spectroscopic analysis and literature reports clearly validate the mechanistic insight of this sensing strategy i.e., the initial formation of 1,2,3,4-oxatriazole on treatment of the probe with NO which finally converted to its carboxylic acid derivative. This oxatriazole formation results in a drastic enhancement in fluoroscence intensity due to the photoinduced electron transfer (PET) effect. The kinetic investigation unveils the second and first-order dependency on [NO] and [BCM] respectively. The very low detection limit (16 nM), high fluorescence enhancement (123 fold) in aqueous medium and good formation constant (Kf = (4.33 ± 0.48) × 104 M-1) along with pH invariability, non-cytotoxicity, biocompatibility and cell permeability make this probe a very effective one for tracking NO intracellularly. This journal is
- Ali, Mahammad,Dutta, Ananya,Islam, Abu Saleh Musha,Katarkar, Atul,Maiti, Debjani,Sasmal, Mihir
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- Synthesis, cytotoxicity and in silico study of some novel benzocoumarin-chalcone-bearing aryl ester derivatives and benzocoumarin-derived arylamide analogs
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The development of new prostate cancer protein receptor cytochrome P450 17A1 inhibitors offers the possibility of generating structures of increased potency. To this end, the chalcone analogs 7 and 8 were prepared from treatment of methyl 3-oxo-3H-benzocoumarin-2-carboxylate (4) with aryl aldehydes. Treatment of 7 and 8 with three anti-inflammatory drugs, flurbiprofen, ketoprofen and ibuprofen, in the presence of POCl3/DMAP gave the ester analogs 9-12. Analogously, treatment of ethyl 3-oxo-3H-benzocoumarin-2-carboxylate (15), prepared previously from 2-hydroxy-1-naphthaldehyde (13) and dimethylmalonate (14), with various arylamines: 4-bromoaniline, 2-amino-6-methylpyridine, amino-antipyrine and 2-amino-5-nitrothiazole, in the presence of potassium tert-butoxide gave the benzocoumarine-3-arylamide analogs. The in vitro cytotoxic activities of 9-12 and 16-19 were evaluated against human prostate cancer cell lines (PC-3) and normal human liver epithelia (WRL-68) by MTT assay. Compounds 10 and 17 were the most active cytotoxic agents among the series against PC-3 cells with IC50 values of 71.35 and 78.25 μg mL-1 with SI values of 3.0 and 4.2, respectively (calculated from the cytotoxicity effects of 10 and 17 on the normal human liver epithelia [WRL-68]). Furthermore, compounds 11 and 12 were tested against breast cancer (HER2 cell lines), prostate cancer (DU-135 cell lines) and MCF-7 but were inactive. Molecular docking studies between the protein receptor CYPP450 17A1 and compounds 10 and 17 revealed that these compounds primarily form hydrophobic interactions with the receptor.
- Abdul-Ridha, Nabeel A.,Salmaan, Afraah D.,Sabah, Rita,Saeed, Bahjat,Al-Masoudi, Najim A.
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p. 201 - 210
(2021/04/26)
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- A two-photon benzocoumarin-NBD dyad for highly selective and sensitive ratiometric detection of H2S in biological samples
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Hydrogen sulfide (H2S), the third endogenous gas signaling transmitter, plays an important role in the basic signal conduction process of human physiology and pathology. It is critical to monitor the dynamic change of H2S in living organisms. In this article, a two-photon ratiometric fluorescent probe (BCD) based on the benzocoumarin-NBD framework was first designed and synthesized. The probe showed large emission separation (about 115 nm), excellent selectivity, and high sensitivity. Moreover, it could be applied to ratiometric image endogenous H2S biosynthesis in the living cells and zebrafish.
- Chen, Guofeng,Gao, Jingshuo,Guo, Zhenbo,Jia, Xu,Li, Xiaoliu,Wei, Chao,Wei, Lingyu,Yang, Shuhan,Zhang, Pingzhu
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- Au(I)-Catalyzed Domino Cyclization of 1,6-Diynes Incorporated with Indole
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We disclose herein a Au(I)-catalyzed domino cyclization of 1,6-diynes incorporated with indole. This protocol enabled the diastereoselective buildup of indole-fused azabicyclo[3.3.1]nonanes from linear precursors. Density functional theory calculations showed that the reaction proceeded via an unprecedented cascade dearomatization/rearomatization/dearomatization process. Independent gradient model analysis revealed that a noncovalent attractive interaction between the distal alkyne and the Au/proximal complex was responsible for the chemoselectivity of the first spirocyclization step.
- Chen, Guzhou,Liu, Peng-Yu,Zou, Huanhuan,Hu, Jiadong,Fang, Xiaowu,Xu, Dongyang,He, Yu-Peng,Wei, Hongbo,Xie, Weiqing
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supporting information
p. 2279 - 2284
(2021/04/05)
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- Enantioselective Construction of Spirooxindole-Fused Cyclopentanes
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The present study reports an asymmetric organocatalytic cascade reaction of oxindole derivates with α,β-unsaturated aldehydes efficiently catalyzed by simple chiral secondary amine. Spirooxindole-fused cyclopentanes were produced in excellent isolated yields (up to 98%) with excellent enantiopurities (up to 99% ee) and moderate to high diastereoselectivities. The synthetic utility of the protocol was exemplified on a set of additional transformations of the corresponding spiro compounds. In addition, a study showing the promising biological activity of selected enantioenriched products was accomplished.
- Do?ekal, Vojtěch,Vopálenská, Andrea,Měrka, Pavel,Kone?ná, Klára,Jand'Ourek, Ond?ej,Pour, Milan,Císa?ová, Ivana,Vesely, Jan
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p. 12623 - 12643
(2021/07/31)
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- Zirconium(IV) oxychloride: A simple and efficient catalyst for the synthesis of chromen-2-one derivatives
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The present work explores a highly efficient, environmental friendly, green protocol for the synthesis of chromen-2-one derivatives (3a-m) by the condensation of salicylaldehydes with various active methylene compounds using zirconium (IV) oxychloride as catalyst. This is a convenient and rapid method for Knoevenagel condensation and this methodology offers several advantages including shorter reaction time, milder conditions, inexpensive catalyst, simple operational procedure and allowed to achieve the desired products in excellent yields. The structures of all the synthesized compounds were confirmed by spectral data.
- TASQEERUDDIN,ASIRI, YAHYA I.,SHAHEEN
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p. 2611 - 2616
(2020/10/22)
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- Fluorescent probe, preparation method thereof, fluorescent probe test paper, and application of fluorescent probe test paper
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The invention belongs to the technical field of biological mercaptan detection, and particularly relates to a fluorescent probe, a preparation method thereof, a fluorescent probe test paper, and an application of the fluorescent probe test paper. The fluorescent probe can specifically recognize biological mercaptan (Cys, Hcy and GSH), and has the advantages of easiness in preparation, low price, strong specificity, high sensitivity, and suitableness for the physiological pH; and the fluorescent probe test paper prepared by using the fluorescent probe can be used to quantitatively detect biological mercaptan in a urine sample through naked eyes, and has great application values in the fields of biomedicines and the like.
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Paragraph 0065-0068
(2020/02/19)
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- Tandem Olefin Isomerization/Cyclization Catalyzed by Complex Nickel Hydride and Br?nsted Acid
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We disclose a nickel/Br?nsted acid-catalyzed tandem process consisting of double bond isomerization of allyl ethers and amines and subsequent intramolecular reaction with nucleophiles. The process is accomplished by [(Me3P)4NiH]N(SO2CF3)2 in the presence of triflic acid. The methodology provides rapid access to tetrahydropyran-fused indoles and other oxacyclic scaffolds under very low catalyst loadings.
- Kathe, Prasad M.,Caciuleanu, Alexandru,Berkefeld, Andreas,Fleischer, Ivana
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p. 15183 - 15196
(2020/11/30)
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- AZEPINO-INDOLES AND OTHER HETEROCYCLES FOR TREATING BRAIN DISORDERS
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The present invention provides azepino-indoles and other heterocycles and methods of using the compounds for treating brain disorders.
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Paragraph 0204
(2020/09/12)
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- Improved and Flexible Synthetic Access to the Spiroindole Backbone of Cebranopadol
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By changing the dimethylamino to a nitro group, a novel synthetic access to the spirocyclic opioid analgesic cebranopadol was developed that is much more efficient compared with the established route. On the basis of the α-acidity of α-nitrotoluene, the two-fold Michael addition to acrylate gave an acyclic precursor compound, which was easily transformed by Dieckmann condensation and decarboxylation to the cyclohexanone derivative needed for the annulation of the indole ring by an oxa-Pictet-Spengler reaction. As an additional benefit, the reduction of the nitro group furnished an amine, which could be late-stage-diversified to carboxamides, sulfonamides, ureas, and N-alkyl congeners. The transformation of the nitro group at the spirocyclic scaffold to the dimethylamino function of the actual title compound was achieved in one step with zinc/formic acid/formaldehyde in 83% yield.
- Christoffers, Jens,Schmidtmann, Marc,Wachtendorf, Daniel
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supporting information
p. 6420 - 6423
(2020/09/02)
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- Supramolecular synthesis of coumarin derivatives catalyzed by a coordination-assembled cage in aqueous solution
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A self-assembled Pd4L2 cage is employed as a water-soluble molecular flask for the synthesis of functionalized coumarins from a series of salicylaldehyde derivatives and cyanoacetates/malononitrile. The catalytic reaction features mild aqueous conditions and broad substrate scope. Crystal structures of the host-guest complexes for two substrates and one analogous intermediate have been obtained, shedding light on the supramolecular reaction mechanism. Michaelis-Menten kinetic studies were performed in one typical case, revealing that the rate of product formation has been enhanced by over 23-fold in contrast to the background reaction without cage. Moreover, the same reaction catalyzed by a smaller Pd6L4 cage gives a mixture of products and much lower yields, suggesting that fine-tuning on the size and symmetry of the cages’ cavity is crucial for their applications in supramolecular catalysis.
- Li, Shao-Chuan,Cai, Li-Xuan,Zhou, Li-Peng,Guo, Fang,Sun, Qing-Fu
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p. 713 - 718
(2019/03/27)
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- Novel strategy of constructing fluorescent probe for MAO-B via cascade reaction and its application in imaging MAO-B in human astrocyte
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To detect monoamine oxidase B (MAO-B), the level of which is one of the most important indicators of neurodegenerative diseases such as Parkinson's disease, a new type of cascade reaction based on the formation of coumarin was applied in this research. After the reaction with MAO-B, the protecting group of hydroxyl group in probes (DEAN-MA and DEAB-MA) was removed, and the fluorescence intensity significantly increased (λem = 456 nm) as the structure of coumarin was formed subsequently. The probes showed excellent sensitivity and selectivity to MAO-B. The detection limit of DEAN-MA and DEAB-MA were 0.6 ng/mL and 0.2 ng/mL, respectively. We succeeded in detecting MAO-B in vitro and imaging it in human astrocyte (U87).
- Qin, Huihuan,Li, Lingling,Li, Kun,Xiaoqi, Yu
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supporting information
p. 71 - 74
(2018/05/26)
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- Rapid One-Pot Access to Unique 3,4-Dihydrothiopyrano[3,4-b]indol-1(9H)-imines via Bi(OTf)3-Catalysed Tandem Friedel–Crafts Alkylation/Thia-Michael Addition
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A highly efficient and atom economical one-pot annulation strategy for novel tetrahydrothiopyrano[3,4-b]indoles is presented. This protocol involves a Bi(OTf)3 catalyzed tandem Friedel–Crafts alkylation and intramolecular thia-Michael addition reactions to furnish target molecules in an efficient manner. The method works effectively on substrates with unprotected indoles and also it is successfully employed to make tetrahydrothiepino[3,4-b]indoles. The scaffolds synthesized are diverse and first of the kind. The reaction is practically simple with broad substrate scope and vast functional group compatibility.
- Dethe, Dattatraya H.,Boda, Vijay Kumar,Mandal, Anupam
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supporting information
p. 5417 - 5421
(2018/10/20)
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- Development of the Vinylogous Pictet–Spengler Cyclization and Total Synthesis of (±)-Lundurine A
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A novel vinylogous Pictet–Spengler cyclization has been developed for the generation of indole-annulated medium-sized rings. The method enables the synthesis of tetrahydroazocinoindoles with a fully substituted carbon center, a prevalent structural motif in many biologically active alkaloids. The strategy has been applied to the total synthesis of (±)-lundurine A.
- Nash, Aaron,Qi, Xiangbing,Maity, Pradip,Owens, Kyle,Tambar, Uttam K.
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supporting information
p. 6888 - 6891
(2018/05/08)
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- Palladium-Catalyzed Asymmetric Allylic Alkylation of 3-Substituted 1 H-Indoles and Tryptophan Derivatives with Vinylcyclopropanes
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Vinylcyclopropanes (VCPs) are known to generate 1,3-dipoles with a palladium catalyst that initially serve as nucleophiles to undergo [3 + 2] cycloadditions with electron-deficient olefins. In this report, we reverse this reactivity and drive the 1,3-dipoles to serve as electrophiles by employing 3-alkylated indoles as nucleophiles. This represents the first use of VCPs for the completely atom-economic functionalization of 3-substituted 1H-indoles and tryptophan derivatives via a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA). Excellent yields and high chemo-, regio-, and enantioselectivities have been realized, providing various indolenine and indoline products. The method is amenable to gram scale and works efficiently with tryptophan derivatives that contain a diketopiperazine or diketomorpholine ring, allowing us to synthesize mollenine A in a rapid and ligand-controlled fashion. The obtained indolenine products bear an imine, an internal olefin, and a malonate motif, giving multiple sites with diverse reactivities for product diversification. Complicated polycyclic skeletons can be conveniently constructed by leveraging this unique juxtaposition of functional groups.
- Trost, Barry M.,Bai, Wen-Ju,Hohn, Christoph,Bai, Yu,Cregg, James J.
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supporting information
p. 6710 - 6717
(2018/05/24)
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- PhI(OAc)2 mediated an efficient Knoevenagel reaction and their synthetic application for coumarin derivatives
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A phenyliododiacetate (PhI(OAc)2) mediated an efficient and novel protocol for the Knoevenagel reaction has been successfully accomplished. A base free, simple and straightforward method afforded wide substrate scope and good functional group tolerance, having high yields (80–92%) under environmentally benign and mild reaction conditions.
- Khan, Danish,Mukhtar, Sayeed,Alsharif, Meshari A.,Alahmdi, Mohammed Issa,Ahmed, Naseem
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supporting information
p. 3183 - 3187
(2017/07/18)
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- A Photoredox-Induced Stereoselective Dearomative Radical (4+2)-Cyclization/1,4-Addition Cascade for the Synthesis of Highly Functionalized Hexahydro-1H-carbazoles
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A stereoselective synthesis of functionalized hexahydrocarbazoles was developed based on an unprecedented photoredox-induced dearomative radical (4+2)-cyclization/1,4-addition cascade between 3-(2-iodoethyl)indoles and acceptor-substituted alkenes. The title reaction simultaneously generates three C?C bonds and one C?H bond, along with three contiguous stereogenic centers. The hexahydro-1H-carbazole products are highly valuable intermediates for the synthesis of novel antibiotics, as well as unnatural ring homologues of polycyclic indoline alkaloids.
- Alpers, Dirk,Gallhof, Malte,Witt, Julian,Hoffmann, Frank,Brasholz, Malte
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supporting information
p. 1402 - 1406
(2017/01/24)
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- Scope of the Reactions of Indolyl- and Pyrrolyl-Tethered N-Sulfonyl-1,2,3-triazoles: Rhodium(II)-Catalyzed Synthesis of Indole- and Pyrrole-Fused Polycyclic Compounds
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An efficient synthesis of tetrahydrocarboline-type products and polycyclic spiroindolines has been achieved. The transformation proceeds via rhodium(II)-catalyzed intramolecular annulations of indolyl- and pyrrolyl-tethered N-sulfonyl-1,2,3-triazoles. The reaction could be tuned toward either the formal [3 + 2] cycloaddition or the C-H functionalization reaction depending on the electronic and structural features of the substrates, leading to the production of a variety of structurally related heterocyclic compounds.
- Fu, Liangbing,Davies, Huw M. L.
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supporting information
p. 1504 - 1507
(2017/04/13)
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- Structure-guided design of new indoles as negative allosteric modulators (NAMs) of N-methyl-d-aspartate receptor (NMDAR) containing GluN2B subunit
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Negative allosteric modulators (NAMs) of GluN2B-containing NMDARs provide pharmacological tools for the treatment of chronic neurodegenerative diseases. Novel NAMs have been designed on the basis of computational studies focused on the 'hit compound' 3. This series of indoles has been tested in competition assay. Compounds 16 and 17 were the most active ligands (IC50 values of 83 nM and 71 nM, respectively) and they showed a potency close to that of reference compounds ifenprodil (1, IC50 = 47 nM) and 3 (IC50 = 25 nM). Furthermore, docking studies have been performed for active ligand 16 and the results were in a good agreement with biological data.
- Buemi, Maria Rosa,De Luca, Laura,Ferro, Stefania,Russo, Emilio,De Sarro, Giovambattista,Gitto, Rosaria
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p. 1513 - 1519
(2016/03/15)
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- Coumarin-3-carboxylic acid ester derivative preparation method
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The invention discloses a preparation method for a coumarin-3-carboxylic ester derivative shown as the formula (I) or the formula (II) in the specification. The method comprises the step that under the existence of FeCl3 being used as a catalyst, salicylaldehyde derivative shown as the formula (III) in the specification and 2-hydroxy-1-naphthaldehyde shown as the formula (IV) in the specification are in contact reaction with alcohol and meldrum's acid which have a general formula, namely R2OH. Through the fact that the salicylaldehyde derivative, the 2-hydroxy-1-naphthaldehyde, the alcohol or the meldrum's acid is catalyzed by FeCl3 in multi-component contact reaction under a relatively temperate condition, the coumarin-3-carboxylic ester derivative with relatively high productivity is synthesized in relatively short reaction time, and the method is simple in step, efficient and environment-friendly, and completely meets the concept of green chemistry.
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Paragraph 0207; 0212-0216
(2017/02/02)
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- Synthesis, fluorescence properties, and antiproliferative potential of several 3-oxo-3H-benzo[f]chromene-2-carboxylic acid derivatives
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In this study, two series of 3-oxo-3H-benzo[f]chromene-2-carboxylic acid derivatives (compounds 5a-i and 6a-g) were synthesized. Their in vitro proliferation inhibitory activities against the A549 and NCI-H460 human non-small cell lung cancer (NSCLC) cell lines were evaluated. Their photophysical properties were measured. Among these target compounds, 5e exhibited the strongest antiproliferative activity by inducing apoptosis, arresting cell cycle, and elevating intracellular reactive oxygen species (ROS) level, suggesting that it may be a potent antitumor agent. In addition, compound 6g with very low cytotoxicity, demonstrated excellent fluorescence properties, which could be used as an effective fluorescence probe for biological imaging.
- Fu, Xiao-Bo,Wang, Xian-Fu,Chen, Jia-Nian,Wu, De-Wen,Li, Ting,Shen, Xing-Can,Qin, Jiang-Ke
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p. 18565 - 18584
(2015/11/11)
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- Synthesis of coumarin-3-carboxylic esters via FeCl3-catalyzed multicomponent reaction of salicylaldehydes, Meldrum's acid and alcohols
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A FeCl3-catalyzed multicomponent reaction was developed for the facile synthesis of coumarin-3-carboxylic ester derivatives in a highly atom-economic and environmentally friendly way. Using simple and cheaply available salicylaldehydes, Meldrum's acid and alcohols as the starting materials, the method needs no extra additives and features wide substrate scope, good functional group tolerance and mild reaction conditions.
- He, Xinwei,Shang, Yongjia,Zhou, Yao,Yu, Zhiyu,Han, Guang,Jin, Wenjing,Chen, Jiaojiao
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p. 863 - 868
(2015/01/30)
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- Condensation of salicylaldehydes with ethyl 4,4,4-trichloro-3-oxobutanoate: A facile approach for the synthesis of substituted 2H-chromene-3-carboxylates
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A highly efficient and simple protocol has been developed for the preparation of ethyl 2-oxo-2H-chromene-3-carboxylates 3a-v by the condensation of salicylaldehydes 1a-v with ethyl 4,4,4-trichloro-3-oxobutanoate 2 for the first time. The reaction is proceeding via Knoevenagel pathway followed by a selective addition of the phenolic hydroxyl group to the carbonyl group adjacent to the CCl3 group rather than ester carbonyl due to a strong electron withdrawing effect and produced coumarin derivative 3a with the elimination of CHCl3.
- Sairam, Mudulkar,Saidachary, Gannerla,Raju, Bhimapaka China
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supporting information
p. 1338 - 1343
(2015/03/04)
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- FeCl3-catalyzed cascade reaction: An efficient approach to functionalized coumarin derivatives
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An efficient and environmentally benign synthesis of 3-substituted or 3,4-disubstituted coumarins was accomplished via iron(III) chloride-catalyzed cascade reactions of salicylaldehydes and activated methylene compounds. The reaction preceded cleanly under mild reaction conditions to provide the desired coumarin derivatives in good to excellent yields.
- He, Xinwei,Yan, Zhenglei,Hu, Xiaoqian,Zuo, Yin,Jiang, Chang,Jin, Lei,Shang, Yongjia
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supporting information
p. 1507 - 1514
(2014/05/20)
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- Dearomatization of tryptophols via a vanadium-catalyzed asymmetric epoxidation and ring-opening cascade
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An enantioselective epoxidation of tryptophols followed by an intramolecular epoxide opening reaction was realized by chiral vanadium catalysts derived from C2 symmetric bis-hydroxamic acid (BHA) ligands. 3a-Hydroxyfuroindoline derivatives with up to 89% yield and 90% ee were obtained under mild reaction conditions.
- Han, Long,Liu, Chuan,Zhang, Wei,Shi, Xiao-Xin,You, Shu-Li
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supporting information
p. 1231 - 1233
(2014/02/14)
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- Synthesis of 1-indolyl substituted β-carboline natural products and discovery of antimalarial and cytotoxic activities
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A series of 1-indolyl substituted β-carbolines including the natural products hyrtiosulawesine, pityriacitrin and pityriacitrin B were prepared via Pictet-Spengler condensation - oxidation strategy from the corresponding indolyl-acetaldehydes and substituted tryptamines. Efforts to prepare the C-1 methylene-linked β-carboline analogues for structure-activity relationship studies were unsuccessful. Biological evaluation revealed two analogues (5 and 41) to exhibit weak inhibition of phospholipase A2 (IC50 171 and 131 μM, respectively), two to act as antioxidants (3 and 43), and 12 analogues with activity towards a chloroquine-resistant strain (FcB1) of Plasmodium falciparum (IC50 1.0-23 μM). Testing against a panel of 60 human tumour cell lines revealed a general lack of cytotoxic effect for most of the compounds with the exception of β-carboline 42 exhibiting modest antileukaemic activity towards the HL-60(TB) cell line (LC50 4.2 μM). In addition, two novel structures (30 and 32) resulting from aldol condensation followed by Pictet-Spengler cyclisation displayed cytotoxicity with pronounced subpanel specificities towards colon cancer (COLO 205 and HCC-2998) cell lines.
- Liew, Lydia P.P.,Fleming, Jessica M.,Longeon, Arlette,Mouray, Elisabeth,Florent, Isabelle,Bourguet-Kondracki, Marie-Lise,Copp, Brent R.
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p. 4910 - 4920
(2014/07/07)
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- SMALL MOLECULE INDUCERS OF GDNF AS POTENTIAL NEW THERAPEUTICS FOR NEUROPSYCHIATRIC DISORDERS
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The invention provides a compound having the structure (I), wherein A is a substituted or unsubstituted ring; Z is present or absent and when present is (II), wherein n is 0, 1, 2, 3, or 4; Y is -(CR11R12)-, -NH(CR11R12)- or -O(CR11R12)- wherein R11 and R12 are each hydrogen or combine to form a carbonyl; and wherein R1 to R10 are herein as described.
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Page/Page column 101; 102
(2013/03/26)
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- Bidirectional synthesis of montamine analogs
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Reported herein is a bidirectional synthesis of symmetric N,N′-diacyl hydrazide compounds closely resembling the alkaloid natural product montamine. In the process, di-tert-butyl hydrazine-1,2-dicarboxylate was smoothly dialkylated with alkyl halides, then Boc deprotected and acylated with an acetate-protected acid chloride derived from ferulic acid. After acetate removal, simple montamine analogs were obtained in excellent overall yields. Fischer indole synthesis with 4-methoxyphenylhydrazine hydrochloride and dihydrofuran provided 5-methoxytryptophol, which was then elaborated to the 1,2-bis(5-methoxyindol-3-yl)hydrazide structure bearing the substitution pattern found in montamine.
- Freitas, Melanie B.,Simollardes, Kelly A.,Rufo, Caroline M.,McLellan, Chantel N.,Dugas, Gabrielle J.,Lupien, Leslie E.,Davie, Elizabeth A. Colby
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supporting information
p. 5489 - 5491
(2013/09/23)
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- A tandem isomerization/prins strategy: Iridium(III)/Bronsted acid cooperative catalysis
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Working together: A mild and efficient isomerization/protonation sequence generates pyran-fused indoles by cooperative catalysis between cationic iridium(III) and Bi(OTf)3. Three distinct cyclization manifolds lead to the corresponding bioactive scaffolds in good yields. In addition, N-substituted indoles can be synthesized enantioselectively in the presence of a chiral phosphate. Copyright
- Lombardo, Vince M.,Thomas, Christopher D.,Scheidt, Karl A.
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supporting information
p. 12910 - 12914
(2014/01/06)
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- Fischer indole synthesis in low melting mixtures
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Functionalized indoles are synthezised under mild conditions in a tartaric acid-dimethylurea melt. The melt serves as the solvent and as the catalyst. Under these reaction conditions, sensitive functional groups such as N-Boc, N-Cbz, or azides are stable, and indolenines are obtained regioselectively in excellent yields. The practical use of the method is demonstrated in the synthesis of the hormone melatonin.
- Gore, Sangram,Baskaran, Sundarababu,K?nig, Burkhard
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supporting information
p. 4568 - 4571
(2012/10/30)
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- NOVEL PYRAZOLE AND IMIDAZOLE DERIVATIVES USEFUL AS OREXIN ANTAGONISTS
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The present invention relates to pyrazole and imidazole derivatives of formula (I) wherein U, V, L, X, Y, R1, (R2)n and (R3)m and ring A are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.
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- Synthesis of new benzocoumaryl oxadiazolyls as strong blue-green fluorescent brighteners
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The benzocoumarin-3-ethylcarboxylate 2 on treatment with hydrazine hydrate at room temperature afforded benzocoumarin-3-carbohydrazide 3. The compound 3 served as key intermediate in the synthesis of the title compounds. Thus, benzocoumarin-1,3,4-oxadiazolyls 6a-e were obtained in two ways, i.e. one by direct cyclization of benzocoumarin-3-carbohydrazide 3 with substituted benzoic acids in POCl3 and the other by cyclization of Schiff bases of compounds 5a-e in the presence of bromine/acetic acid. The structures of the novel benzocoumaryl oxadiazolyls 6a-e were confirmed by spectral analysis. The benzocoumarin-1,3,4- oxadiazolyls 6a-e exhibited strong blue and green fluorescent properties. The Stoke's shifts range from 43 to 165 nm. The absorption and fluorescence maxima of the benzocoumaryl oxadiazolyls showed good bathochromic shifts.
- Rajesha,Kiran Kumar,Bhojya Naik,Mahadevan
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experimental part
p. 88 - 94
(2012/06/18)
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- Biocatalytic domino reaction: Synthesis of 2H-1-benzopyran-2-one derivatives using alkaline protease from Bacillus licheniformis
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A novel BLAP (alkaline protease from Bacillus licheniformis) catalyzed synthesis of 2H-1-benzopyran-2-one derivatives was achieved by domino Knoevenagel/intramolecular transesterification reaction. The control of enzymatic chemoselectivity between Knoevenagel/intramolecular transesterification and Knoevenagel/intramolecular hemiketalization could be realized by adjusting parameters including solvent, water content and temperature. The products were obtained in acceptable yields. This BLAP catalyzed selective domino reaction provided an alternative synthetic method for 2H-1-benzopyran-2-one derivatives.
- Wang, Chang-Heng,Guan, Zhi,He, Yan-Hong
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experimental part
p. 2048 - 2054
(2011/10/03)
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- Direct synthesis of dihydrobenzo[a]carbazoles via palladium-catalyzed domino annulation of indoles
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A straightforward one-step synthesis of annulated indoles via palladium-catalyzed, norbornene-mediated sequential intermolecular aryl ortho-alkylation/intramolecular indole C-H activation has been devised. This method provides an efficient route to a wide variety of substituted 6,11-dihydro-5H-benzo[a]carbazoles from readily accessible 3-bromoalkylindoles and iodoarenes.
- Jafarpour, Farnaz,Hazrati, Hamideh
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supporting information; experimental part
p. 363 - 367
(2010/06/11)
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- Synthesis and photoluminescent properties of two novel tripodal compounds containing coumarin moieties
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Two novel tripodal compounds, tris[2-(7-diethylamino-coumarin-3-carboxamide)ethyl]amine (Tren-C1) and tris[2-(benzo[5,6]coumarin-3-carboxamide)ethyl]amine (Tren-C2), were synthesized and characterized. The UV-vis and fluorescence properties of Tren-C1 and Tren-C2 in solutions were investigated. These two compounds exhibited strong blue emission under ultraviolet light excitation. The maximal fluorescence emission occurred at about the level of 10-5 mol/L. The chromophore units in the tripodal compounds shown a little interaction in the ground state, while the interactions in the excited state was notable and which leads to a broad and bathochromic shift of the emission bands.
- Yu, Tianzhi,Zhang, Peng,Zhao, Yuling,Zhang, Hui,Meng, Jing,Fan, Duowang
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scheme or table
p. 168 - 173
(2009/06/20)
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- Novel 3-carboxamide-coumarins as potent and selective FXIIa inhibitors
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Recently, FXIIa was highlighted as an original attractive target for the development of new anticoagulant drugs with low rates of therapy-related hemorrhages. In this work, we describe the development of a new series of 3-carboxamide-coumarins that are the first potent and selective nonpeptidic inhibitors of FXIIa.
- Robert, Séverine,Bertolla, Carine,Masereel, Bernard,Dogné, Jean-Michel,Pochet, Lionel
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supporting information; experimental part
p. 3077 - 3080
(2009/04/07)
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- Microwave assisted synthesis of coumarins via potassium carbonate catalyzed knoevenagel condensation in 1-n-butyl-3-methylimidazolium bromide ionic liquid
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(Chemical Equation Presented) A variety of substituted coumarins have been prepared via an inexpensive and efficient potassium carbonate catalyzed Knoevenagel condensation of salisylaldehydes with acidic methylene compounds in ionic liquid media. 1-n-Butyl-3-methylimidazolium bromide has been employed as an alternative reaction medium in this procedure. The reaction proceeds smoothly under mild and solvent-free conditions and the products are obtained in excellent yields. Mild reaction conditions and good to excellent yields of the products are the noteworthy advantages of the method.
- Valizadeh, Hassan,Shockravi, Abbas,Gholipur
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p. 867 - 870
(2008/04/12)
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- Syntheses, characterization and fluorescent properties of two triethylene-glycol dicoumarin-3-carboxylates
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Two novel triethylene-glycol dicoumarin-3-carboxylates were synthesized and characterized by element analysis, 1H NMR, FT-IR and UV-vis absorption spectra. The photoluminescent behaviors of triethylene-glycol dibenzo[5,6]coumarin-3-carboxylate doped in PMMA were discussed. These compounds exhibit strong blue emission under ultraviolet light excitation. Compared to coumarin-3-triethylene glycol diester, the absorption and emission spectra of benzo[5,6]coumarin-3-triethylene glycol diester was bathochromically shifted due to the larger conjugation of benzene moiety. These derivatives have potential possible to explore organic electroluminescent materials.
- Zhang, Hui,Yu, Tianzhi,Zhao, Yuling,Fan, Duowang,Qian, Long,Yang, Changhui,Zhang, Kai
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p. 725 - 727
(2008/02/12)
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- Design, synthesis, and melatoninergic activity of new azido- and isothiocyanato-substituted indoles
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To develop irreversibly binding ligands for the melatonin receptor(s) as tools for tracing the primary melatonin binding site, we report on the design and synthesis of new melatoninergic azido- and isothiocyanato-substituted indoles. All active compounds were partial agonists or antagonists in the Xenopus melanophore assay, the most potent being the 5-OMe C3-substituted azido 45 and isothiocyanato 46 analogues.
- Tsotinis, Andrew,Afroudakis, Pandelis A.,Davidson, Kathryn,Prashar, Anjali,Sugden, David
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p. 6436 - 6440
(2008/03/30)
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- Improvement of fluorescence characteristics of coumarins: Syntheses and fluorescence properties of 6-methoxycoumarin and benzocoumarin derivatives as novel fluorophores emitting in the longer wavelength region and their application to analytical reagents
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To improve the fluorescence characteristics, especially emission wavelength, of coumarins, various 3-substituted-6-methoxycoumarin derivatives were synthesized, and then benzocoumarin derivatives were also synthesized in expectation of the shift to the longer wavelength region by the extension of the conjugated system. Their fluorescence properties were investigated spectrophotometrically in acetonitrile and evaluated from the viewpoint of the intramolecular charge transfer (ICT) between push- and pull-substituents in the ground and the excited states. Among them, benzocoumarin derivatives especially fluoresced in the longer wavelength around 540 nm with remarkably large Stokes shifts beyond 10000 cm-1. Using such fluorophores, some novel fluorescence derivatization reagents for carboxylic acids, alcohols, phenols, and amines were preliminarily prepared as an example, and their derivatized products were also found to fluoresce in the longer wavelength region with large Stokes shifts.
- Murata, Chiyomi,Masuda, Toshinobu,Kamochi, Yasuko,Todoroki, Kenichiro,Yoshida, Hideyuki,Nohta, Hitoshi,Yamaguchi, Masatoshi,Takadate, Akira
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p. 750 - 758
(2007/10/03)
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- Methods for inhibiting deacetylase activity
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A method for identifying a compound that inhibits the NAD+-dependent deacetylase activity of a SIR2 protein is disclosed. These compounds are useful for the treatment of cancers and other diseases, through the activation of silenced genes, through the promotion of apoptosis in cancerous cells, and through the inhibition of transcriptional repressor activity in oncogenes.
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Page/Page column 13
(2008/06/13)
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- Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors
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Previous studies from our laboratory have revealed that esterification/amidation of the carboxylic acid moiety in the nonsteroidal anti-inflammatory drug, indomethacin, generates potent and selective COX-2 inhibitors. In the present study, a series of reverse ester/amide derivatives were synthesized and evaluated as selective COX-2 inhibitors. Most of the reverse esters/amides displayed time-dependent COX-2 inhibition with IC 50 values in the low nanomolar range. Replacement of the 4-chlorobenzoyl group on the indole nitrogen with a 4-bromobenzyl moiety resulted in compounds that retained selective COX-2 inhibitory potency. In addition to inhibiting COX-2 activity in vitro, the reverse esters/amides also inhibited COX-2 activity in the mouse macrophage-like cell line, RAW264.7. Overall, this strategy broadens the scope of our previous methodology of neutralizing the carboxylic acid group in NSAIDs as a means of generating COX-2-selective inhibitors and is potentially applicable to other NSAIDs.
- Kalgutkar, Amit S.,Crews, Brenda C.,Saleh, Sam,Prudhomme, Daniel,Marnett, Lawrence J.
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p. 6810 - 6822
(2007/10/03)
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- Inhibitors of Sir2: Evaluation of Splitomicin Analogues
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Splitomicin (1) and 41 analogues were prepared and evaluated in cell-based Sir2 inhibition and toxicity assays and an in vitro Sir2 inhibition assay. Lactone ring or naphthalene (positions 7-9) substituents decrease activity, but other naphthalene substitutions (positions 5 and 6) are well-tolerated. The hydrolytically unstable aromatic lactone is important for activity. Lactone hydrolysis rates were used as a measure of reactivity; hydrolysis rates correlate with inhibitory activity. The most potent Sir2 inhibitors were structurally similar to and had hydrolysis rates similar to 1.
- Posakony, Jeff,Hirao, Maki,Stevens, Sam,Simon, Julian A.,Bedalov, Antonio
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p. 2635 - 2644
(2007/10/03)
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- A novel substitution reaction of tetrahydropyrano[3,4-b]indole derivative - Chain extension and structural correlation study
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An unusual cyanation with rearrangement of a 1-chloromethyl-tetrahydropyrano[3,4-b]indole-1-acetic acid ester derivative is reported. The resulting C-1 chain extension product is identified by correlation studies and spectral method.
- Chou, Shan-Yen
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p. 1095 - 1110
(2007/10/03)
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- Solvent free synthesis of coumarins
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An efficient synthesis of 3-substituted coumarins under solventless system is described.
- Shockravi, Abbas,Shargi, Hashem,Valizadeh, Hassan,Heravi, Majid M.
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p. 2555 - 2559
(2007/10/03)
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- Lewis acidic ionic liquids for the synthesis of electrophilic alkenes via the Knoevenagel condensation
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1-Butyl-3-methylimidazolium chloroaluminate, [bmim]Cl·AlCl3, N = 0.67 and 1-butylpyridinium chloroaluminate, [bpy]Cl·AlCl3, N = 0.67 ionic liquids were found to work well as the Lewis acid catalyst and solvent in the Knoevenagel condensations of benzaldehyde and substituted benzaldehydes with diethyl malonate to give benzylidene malonates. The benzylidene malonates subsequently underwent Michael additions with diethyl malonate. The extent of Michael product formed during the reaction was found to vary with the Lewis acidity and the molar proportion of ionic liquid. The influence of Lewis acidity of the ionic liquid on the Knoevenagel and Michael products is demonstrated. In the case of 2-hydroxyarylaldehydes, the reactions led to the formation of 3-ethoxycarbonyl coumarins under ambient conditions.
- Harjani, Jitendra R,Nara, Susheel J,Salunkhe, Manikrao M
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p. 1127 - 1130
(2007/10/03)
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- Solvent-free coumarin synthesis
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The synthesis of coumarins via Pechmann and Knoevenagel condensation reactions under solvent-free conditions is reported, in which waste minimization, simple operation and easier product work-up can be achieved.
- Sugino, Teizo,Tanaka, Koichi
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p. 110 - 111
(2007/10/03)
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- One-pot preparation of coumarins by Knoevenagel condensation in solvent-free condition under microwave irradiation
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3-Substituted coumarins were prepared by the Knoevenagel reaction of 2-hydroxybenzaldehyde derivatives and 2-hydroxy-1-naphthaldehyde in the presence of ammonium aceteate on basic alumina or silica gel under microwave irradiation. High yields, low reaction times, being environmentally friendly, elimination of organic base and solvent are advantages of this method.
- Balalaie, Saeed,Nemati, Navid
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- Preparation and reactions of 4-, 5-, and 6-methoxy substituted 3-lithioindoles and 3-indolylzinc derivatives
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The preparation of 4-, 5-, and 6-methoxy substituted 3-lithio-1-(trialkylsilyl)indoles 4b-d by metalation of the corresponding 3-bromoindoles, and their reactions with iodomethane, DMF, ethylene oxide and aziridines are reported. Transmetalation of 3-lithioindoles 4b-d with ZnCl2 afforded 3-indolylzinc chlorides 11b-d, which underwent Pd(0)-catalyzed cross-coupling reactions with 2-halopyridines to give 4-, 5-, and 6-methoxy substituted 3-(2-pyridyl)indoles.
- Amat,Seffar,Llor,Bosch
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p. 267 - 275
(2007/10/03)
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