- Magnetic chitosan nanocomposite: As a novel catalyst for the synthesis of new derivatives of N-sulfonylamidine and N-sulfonylimidate
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This study reports the synthesis and characterization of a highly active catalyst based on chelated copper iodide on magnetic chitosan-salicylaldehyde Schiff base. This catalyst was successfully used for the three-component reaction of N-propargylphthalimide, tosylazide, and NH or OH containing nucleophiles to access new classes of N-sulfonylamidine or N-sulfonylimidate derivatives. The products, which were constructed via an in situ generated sulfonyl keteneimine intermediate, were obtained in good to excellent yields. Short reaction times, easy separation and reusability without significant loss of catalyst activity were found to be the notable features of this synthetic protocol.
- Valizadeh, Sepideh,Ghasemi, Zarrin,Shahrisa, Aziz,Notash, Behrouz,Pirouzmand, Mahtab,Kabiri, Roya
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- New synthesis of trifluorinated amines from 1-bromopropargylic amines in superacid
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Treatment of 1-bromopropargylic amines affords the corresponding 1,1,1-trifluoro in one step in HF-SbF5 medium. 1-Bromo-1,1-difluoro or 2-bromo-1,1,1-trifluoro derivatives could also be prepared, depending on the reaction conditions.
- Cantet, Anne-Céline,Carreyre, Hélène,Gesson, Jean-Pierre,Renoux, Brigitte,Jouannetaud, Marie-Paule
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- Synthesis, antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles
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In a search for safer and potent antitubercular agents, here a library of newly substituted dioxoisoindolinylmethyl-triazolyl-N-phenylacetamide derivatives (5a–l) has been synthesized via click chemistry approach. All synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB). Among the screened compounds, 5d, 5e, 5h, and 5l showed good antitubercular activity. The compounds 5d and 5l have shown very effective antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB) with MIC 12.5 μg/mL. All the newly synthesized compounds were thoroughly characterized by 1H NMR, 13C NMR, and HRMS spectral data. We further performed exploratory docking studies on the crystal structure of Mycobacterium tuberculosis enoyl reductase to demonstrate the mechanism of antitubercular activity.
- Phatak, Pramod S.,Bakale, Rajubai D.,Dhumal, Sambhaji T.,Dahiwade, Lalita K.,Choudhari, Prafulla B.,Siva Krishna, Vagolu,Sriram, Dharmarajan,Haval, Kishan P.
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- Design of molecular hybrids of phthalimide-triazole agents with potent selective MCF-7/HepG2 cytotoxicity: Synthesis, EGFR inhibitory effect, and metabolic stability
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This study reports an efficient and convenient click chemistry synthesis of a novel series of phthalimide scaffold linked to 1,2,3 triazole ring and terminal lipophilic fragments. Structures of newly synthesized compounds were well characterized by different spectroscopic tools. In vitro MTT cytotoxicity assay was performed comparing the cytotoxic effects of newly synthesized compounds to staurosporine using three different types: human liver cancer cell line (HepG2), Michigan cancer foundation-7 (MCF-7) and human colorectal carcinoma cell line (HCT116). The initial screening showed excellent to moderate anticancer activity for these newly synthesized compounds with high degree of cell line selectivity with micromolar (μM) half maximal inhibitory concentration (IC50) values against tumor cells. The SAR analysis of these derivatives confirmed the role of molecular fragments including phthalimide, linker, triazole, and terminal tails in correlation to activity. In addition, enzymatic inhibitory assay against wild type EGFR was performed for the most active compounds to get more details about their mechanism of action. In order to further explore their binding affinities, molecular docking simulation was studied against EGFR site. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated. One of the most prominent analogs is (6f) with terminal disubstituted ring and amide linker showed selective MCF-7 cytotoxicity profile with IC50 0.22 μM and 79 nM to EGFR target. Extensive structure activity relationship (SAR) analyses were also carried out. The pharmacokinetic profile of (6f) was studied showing good metabolic stability and long duration behavior. This design offered a potent selective anticancer phthalimide-triazole leads for further optimization in cancer drug discovery.
- Ihmaid, Saleh K.,Alraqa, Shaya Yahya,Aouad, Mohamed R.,Aljuhani, Ateyatallah,Elbadawy, Hossein M.,Salama, Samir A.,Rezki, Nadjet,Ahmed, Hany E.A.
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- Direct Conversion of Primary Alcohols to 1,2-Amino Alcohols: Enantioselective Iridium-Catalyzed Carbonyl Reductive Coupling of Phthalimido-Allene via Hydrogen Auto-Transfer
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The first catalytic enantioselective carbonyl (α-amino)allylations are described. Phthalimido-allene 1 and primary alcohols 2a-2z, 2a′-2c′ engage in hydrogen auto-transfer-mediated carbonyl reductive coupling by way of (α-amino)allyliridium-aldehyde pairs to form vicinal amino alcohols 3a-3z, 3a′-3c′ with high levels of regio-, anti-diastereo-, and enantioselectivity. Reaction progress kinetic analysis and isotopic labeling studies corroborate a catalytic cycle involving turnover-limiting alcohol dehydrogenation followed by rapid allene hydrometalation.
- Spielmann, Kim,Xiang, Ming,Schwartz, Leyah A.,Krische, Michael J.
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- One-pot enyne metathesis/Diels-Alder reaction for the construction of highly functionalized novel polycyclic aza-compounds
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Various tricyclic dienes were synthesized via enyne metathesis using the first generation Grubbs catalyst. The enyne metathesis proceeded smoothly in refluxing CH2Cl2 with a low catalyst loading (3.0 mol %), giving good yields (72-89%) of the tricyclic products 6 and 16. The resulting 1,3-dienes are suitable precursors of polycyclic structures via a Diels-Alder process. One-pot RCM/Diels-Alder reactions of the enyne products with dienophiles proceeded smoothly to afford polycyclic compounds as a single cycloadduct. The structures of the Diels-Alder adducts were determined by 1H NMR spectra and X-ray analysis. The cycloadducts were formed via the approach of the dienophiles towards the diene in endo mode.
- Ben-Othman, Raja,Othman, Mohamed,Coste, Servane,Decroix, Bernard
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- Potent antiproliferative activity of bradykinin B2 receptor selective agonist FR-190997 and analogue structures thereof: A paradox resolved?
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Βradykinin stimulation of B2 receptor is known to activate the oncogenic ERK pathway and overexpression of bradykinin receptors B1 and B2 has been reported to occur in glioma, colorectal and cervical cancers. B1R and B2R antagonists have been shown to reverse tumor proliferation and invasion. Paradoxically, B1R and B2R agonism has also been reported to elicit antiproliferative benefits. In order to complement the data accumulated to date with the natural substrate bradykinin and peptidic B2R antagonists, we decided to examine for the first time the response elicited by B2R stimulation in breast cancer lines with a non-peptidic small molecule B2R agonist. We synthesized and assessed the highly selective and potent B2R partial agonist FR-190997 in MCF-7 and MDA-MBA-231 breast cancer lines and found it possessed significant antiproliferative activity (IC50 2.14 and 0.08 μΜ, respectively). The modular nature of FR-190997 allowed us to conduct a focused SAR study and discover compound 10 which exhibits subnanomolar antiproliferative activity (IC 50 0.06 nΜ) in the TNBC MDA-MBA-231 cell line. This performance surpasses, in most cases by several orders of magnitude, those of established anticancer agents and FDA-approved breast cancer drugs. In line with the established literature we suggest that this remarkable activity precipitates from a dual mode of action involving agonist-induced receptor internalization/degradation combined with sequestration of functional intracellular B2 receptors and inhibition of the associated endosomal signaling. The latter mode may be realized by appropriate ligands regardless of B2R agonist/antagonist designation which only relates to membrane residing GCPRs. Under this prism the controversy over the antiproliferative effects of B2 agonists and antagonists is potentially neutralized.
- Rassias, Gerasimos,Leonardi, Sofia,Rigopoulou, Dionisia,Vachlioti, Eleanna,Afratis, Konstantinos,Piperigkou, Zoi,Koutsakis, Christos,Karamanos, Nikos K.,Gavras, Haralambos,Papaioannou, Dionissios
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- Electroselective and Controlled Reduction of Cyclic Imides to Hydroxylactams and Lactams
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An efficient and practical electrochemical method for selective reduction of cyclic imides has been developed using a simple undivided cell with carbon electrodes at room temperature. The reaction provides a useful strategy for the rapid synthesis of hydroxylactams and lactams in a controllable manner, which is tuned by electric current and reaction time, and exhibits broad substrate scope and high functional group tolerance even to reduction-sensitive moieties. Initial mechanistic studies suggest that the approach heavily relies on the utilization of amines (e.g., i-Pr2NH), which are able to generate α-aminoalkyl radicals. This protocol provides an efficient route for the cleavage of C-O bonds under mild conditions with high chemoselectivity.
- Bai, Ya,Shi, Lingling,Zheng, Lianyou,Ning, Shulin,Che, Xin,Zhang, Zhuoqi,Xiang, Jinbao
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supporting information
p. 2298 - 2302
(2021/04/05)
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- Discovery of fast-acting dual-stage antimalarial agents by profiling pyridylvinylquinoline chemical space via copper catalyzed azide-alkyne cycloadditions
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To identity fast-acting, multistage antimalarial agents, a series of pyridylvinylquinoline-triazole analogues have been synthesized via CuAAC. Most of the compounds display significant inhibitory effect on the drug-resistant malarial Dd2 strain at low submicromolar concentrations. Among the tested analogues, compound 60 is the most potent molecule with an EC50 value of 0.04 ± 0.01 μM. Our current study indicates that compound 60 is a fast-acting antimalarial compound and it demonstrates stage specific action at the trophozoite phase in the P. falciparum asexual life cycle. In addition, compound 60 is active against both early and late stage P. falciparum gametocytes. From a mechanistic perspective, compound 60 shows good activity as an inhibitor of β-hematin formation. Collectively, our findings suggest that fast-acting agent 60 targets dual life stages of the malarial parasites and warrant further investigation of pyridylvinylquinoline hybrids as new antimalarials.
- Huang, Guang,Solano, Claribel Murillo,Melendez, Joel,Yu-Alfonzo, Sabrina,Boonhok, Rachasak,Min, Hui,Miao, Jun,Chakrabarti, Debopam,Yuan, Yu
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supporting information
(2020/10/13)
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- Radical Carbonyl Propargylation by Dual Catalysis
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Carbonyl propargylation has been established as a valuable tool in the realm of carbon–carbon bond forming reactions. The 1,3-enyne moiety has been recognized as an alternative pronucleophile in the above transformation through an ionic mechanism. Herein, we report for the first time, the radical carbonyl propargylation through dual chromium/photoredox catalysis. A library of valuable homopropargylic alcohols bearing all-carbon quaternary centers could be obtained by a catalytic radical three-component coupling of 1,3-enynes, aldehydes and suitable radical precursors (41 examples). This redox-neutral multi-component reaction occurs under very mild conditions and shows high functional group tolerance. Remarkably, bench-stable, non-toxic, and inexpensive CrCl3 could be employed as a chromium source. Preliminary mechanistic investigations suggest a radical-polar crossover mechanism, which offers a complementary and novel approach towards the preparation of valuable synthetic architectures from simple chemicals.
- Huang, Huan-Ming,Bellotti, Peter,Daniliuc, Constantin G.,Glorius, Frank
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supporting information
p. 2464 - 2471
(2020/12/07)
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- Metal-Free Iodoperfluoroalkylation: Photocatalysis versus Frustrated Lewis Pair Catalysis
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A comparison of two catalytic, metal-free iodoperfluoroalkylation protocols is presented. Frustrated Lewis pairs [ tBu 3P/B(C 6F 5) 3] or phosphines/phosphites under visible light irradiation efficiently mediate the functionalization of non-activated alkenes and alkynes. A comprehensive account of the corresponding substrate scopes as well as insights into the mechanistic details of both reaction pathways are provided.
- Helmecke, Lucas,Spittler, Michael,Schmidt, Bernd M.,Czekelius, Constantin
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supporting information
p. 123 - 134
(2020/09/02)
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- Gold-Catalyzed Regioselective Oxyfluorination/Oxydifluorination vs. Diketonization of Phthalimido-Protected Propargylamines with Selectfluor
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Alkyl- and aryl-substituted N-propargyl phthalimides were used as valuable building blocks for the selective formation of the corresponding α-fluoro, β-phthalimido ketones, α,α-difluoro, β-phthalimido ketones or β-phthalimido α-diketones by means of gold-catalyzed oxyfluorination/oxydifluorination or dioxygenation reactions. The key factors addressing the product selectivity control were determined. The simultaneous assembly of the quinoxaline nucleus and the removal of the phthalimido-protecting group were tested. Reaction mechanisms of the different reaction pathways are assumed.
- Arcadi, Antonio,Marsicano, Vincenzo,Michelet, Véronique
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supporting information
(2022/01/22)
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- 17BETA-HETEROCYCLYL-DIGITALIS LIKE COMPOUNDS FOR THE TREATMENT OF HEART FAILURE
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Disclosed are compounds of formula (I) wherein X, Y, Z are annular atoms comprised in a five-membered carbocyclic or heterocyclic ring, selected from the group consisting of CH, NH, N, O, S; said carbocyclic or heterocyclic ring being optionally substituted with amino (C1-C4) linear or branched alkyl or guanidine or guanidino (C1-C4) linear or branched alkyl; with the proviso that the heterocycle ring is not furyl; n is 0 or 1; R is H or OH; the dotted line represents an optional double bond C=C; the thick line represents a bond in the β configuration; the wavy line represents a bond both in the α and β configuration; their enantiomeric and/or diastereomeric mixtures, their pharmaceutically acceptable salts, their solvates, hydrates; their metabolite and metabolic precursors. The compounds of formula (I) are for use as medicaments, in particular for the treatment of acute or chronic heart failure. Oral administration is also possible.
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Page/Page column 0224; 0229; 0230
(2020/02/13)
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- BTK Inhibitors and uses thereof
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The invention discloses a bruton's tyrosine kinase (BTK) inhibitor and use thereof. Specifically, the invention provides heteroaromatic compounds or stereoisomers, geometrical isomers, tautomers, racemates, nitrogen oxides, hydrates, solvates, metabolites and pharmaceutically acceptable salts or prodrugs thereof, and pharmaceutical compositions containing the heteroaromatic compounds; the invention also discloses use of the heteroaromatic compounds or the pharmaceutical compositions containing the heteroaromatic compounds in preparation of medicines; the medicines can be used for treating autoimmune diseases, inflammatory diseases or proliferative diseases.
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Paragraph 1378-1383
(2020/05/02)
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- Design, synthesis and structure-activity relationships of novel 15-membered macrolides: Quinolone/quinoline-containing sidechains tethered to the C-6 position of azithromycin acylides
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In the search for novel hybrid molecules by fusing two biologically active scaffolds into one heteromeric chemotype, we found that hybrids of azithromycin and ciprofloxacin/gatifloxacin 26j and 26l can inhibit the supercoiling activity of E. coli gyrase by poisoning it in a way similar to fluoroquinolones. This may modestly contribute to their potencies, which are equal to ciprofloxacin against constitutively resistant Staphylococcus aureus, whose growth is not inhibited by the presence of macrolides. In contrast, introduction of quinolines (the 3-quinoline 26b and the 6-quinoline 26o) with an optimized rigid spacer at the 6-OH of azithromycin acylides did not exert significant potency against constitutively resistant S. aureus, despite the fact that the quinoline-containing compounds, exemplified by 26o, were as active as telithromycin against susceptible, inducibly- and efflux-resistant pathogens. The novel dual modes of action involving protein synthesis inhibition and poisoning DNA replication may pave the way for restoration of antibacterial activities of the current macrolides against constitutively resistant clinical isolates.
- Aldrich, Courtney,Brody, Scott,Cushman, Mark,Fan, Bing-Zhi,Hiasa, Hiroshi,Liang, Jian-Hua,Lv, Wei,Yang, Zhao-Yong
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- Construction of 1-Tetralols Bearing Two Contiguous Quaternary Chiral Centers through a Rhodium-Catalyzed Enantioselective Desymmetrization Cascade Reaction
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A novel and efficient access to polyfunctionnalized chiral 1-tetralols, bearing two contiguous quaternary carbon stereocenters, has been developed from various and easily accessible alkynyl-1,3-diketones, through a cascade process including a regioselective alkyne insertion, a 1,4-Rh shift, and a nucleophilic addition step via the desymmetrization of the 1,3-diketone moiety thanks to an appropriate rhodium-chiral diene complex in the presence of arylboronic acids.
- Selmani, Aymane,Darses, Sylvain
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supporting information
p. 2681 - 2686
(2020/03/30)
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- Copper (triazole-5-yl)methanamine complexes onto MCM-41: The synthesis of pyridine-containing pseudopeptides through the 6-: Endo-dig cyclization of 1,5-enynes
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An efficient approach for the synthesis of immobilized copper (triazole-5-yl)methanamine complexes onto MCM-41 (Cu?TZMA?MCM-41), as a novel recyclable nanocatalyst, is described. This nanocatalyst was used for the synthesis of pyridine-containing pseudopeptides through a sequential Ugi/nucleophilic addition/1,5-enyne cyclization reaction and elicited good-to-excellent yields. The nanocatalyst was fully characterized by SEM, EDS, TEM, BET, ICP-OES, TGA, and XRD techniques. Furthermore, the catalyst was recovered by simple filtration and could be used for at least 5 cycles without significant loss of activity.
- Akbarikalani, Neda,Al-Harrasi, Ahmed,Amiri, Kamran,Balalaie, Saeed
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p. 10577 - 10583
(2020/03/30)
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- Cobalt-Catalyzed Regioselective Carboamidation of Alkynes with Imides Enabled by Cleavage of C-N and C-C Bonds
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Through the oxidative addition of cobalt into the N-C(O) bond of phthalimide and the subsequent decarbonylation, we describe an efficient cobalt-catalyzed intermolecular decarbonylative carboamidation of alkynes. High regioselectivities have been achieved for unsymmetrical alkynes (including aryl-alkyl or aryl-aryl) to deliver polysubstituted isoquinolones. To facilitate step economy, a three-component decarbonylative carboamidation of alkynes with phthalic anhydrides and amines has been demonstrated using the current cobalt catalysis.
- Chen, Bing-Zhi,Chen, Qing-An,Hu, Yan-Cheng,Ji, Ding-Wei,Min, Xiang-Ting,Wan, Boshun,Zheng, Hao
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supporting information
p. 3386 - 3391
(2020/04/20)
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00962; 004829
(2020/06/19)
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- Experimental and computational evidence on gold-catalyzed regioselective hydration of phthalimido-protected propargylamines: An entry to β-amino ketones
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The results of our investigations on the Au-catalyzed regioselective hydration reaction of both alkyl- A nd aryl-substituted N-propargyl phthalimides directed to the selective formation of the corresponding β-phthalimido ketones are described. Experimental data, in particular the observed regioselectivity, have been qualitatively supported by quantum-chemical calculations carried out on model systems in the framework of Density Functional Theory (DFT) followed by quantum theory of atoms in molecules (QTAIMS). Our results suggest that the electronic features of the initial adduct between the propargyl triple bond and the Au(i) catalyst, in particular the character of the gold-triple bond interaction, are essential for the observed regioselectivity. Other effects, such as the presence of the solvent and the formation of a H-bond between the water molecule and the phthalimido moiety, although apparently irrelevant for the regioselectivity, have proven to be kinetically and catalytically rather important. This journal is
- Arcadi, Antonio,Aschi, Massimiliano,Marsicano, Vincenzo,Michelet, Véronique
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supporting information
p. 9438 - 9447
(2020/12/15)
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- Design, synthesis, and in silico studies of novel eugenyloxy propanol azole derivatives having potent antinociceptive activity and evaluation of their β-adrenoceptor blocking property
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The design, synthesis, antinociceptive and β-adrenoceptor blocking activities of several eugenyloxy propanol azole derivatives have been described. In this synthesis, the reaction of eugenol with epichlorohydrin provided adducts 3 and 4 which were N-alkylated by diverse azoles to obtain the eugenyloxy propanol azole analogues in good yields. Adducts 3 and 4 were also reacted with azide ion to obtain the corresponding azide 6. The ‘Click’ Huisgen cycloaddition reaction of 6 with diverse alkynes afforded the title compounds in good yields. The synthesized eugenyloxy propanol azole derivatives were in vivo studied for the acute antinociception on male Spargue Dawley rats using tail-flick test. Compounds 5f, 5g, 7b and 11a exhibited potent analgesic properties in comparison with eugenol as a standard drug. In addition, all compounds were ex vivo tested for β-adrenoceptor blocking properties on isolated left atrium of male rats which exhibited partial antagonist or agonist behaviour compared to the standard drugs. The molecular docking study on the binding site of transient receptor potential vanilloid subtype 1 (TRPV1) has indicated that like capsaicin, eugenyloxy propanol azole analogues exhibited the strong affinity to bind at site of TPRV1 in a “tail-up, head-down” conformation and the presence of triazolyl moieties has played undeniable role in durable binding of these ligands to TRPV1. The in silico pharmacokinetic profile, drug likeness and toxicity predictions carried out for all compounds determined that 5g can be considered as potential antinociceptive drug candidate for future research.
- Behrouz, Somayeh,Soltani Rad, Mohammad Navid,Taghavi Shahraki, Bahareh,Fathalipour, Mohammad,Behrouz, Marzieh,Mirkhani, Hossein
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p. 147 - 164
(2018/08/22)
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- Palladium-Catalyzed Cyclization Reaction of Oxime Acetates and Aryl Iodides: Syntheses of 2-Imidazolines
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A novel and versatile method for the synthesis of 2-imidazolines has been developed via the Pd-catalyzed cyclization reaction of readily available homoallenyl oxime acetates with aryl iodides. This protocol is performed under mild reaction conditions and needs no additives or ligands.
- Hu, Jinxing,Li, Zefei,Zhang, Xian,Han, Yufei,Liu, Yue,Zhao, Yanfang,Liu, Yajing,Gong, Ping
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supporting information
p. 2116 - 2119
(2018/04/14)
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- Divergent Synthesis of CF3-Substituted Allenyl Nitriles by Ligand-Controlled Radical 1,2- and 1,4-Addition to 1,3-Enynes
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A ligand-controlled system that enables regioselective trifluoromethylcyanation of 1,3-enynes has been identified, which provides access to a variety of CF3-containing tri- and tetrasubstituted allenyl nitriles. We disclose that the involved propargylic radicals can be selectively trapped by (Box)CuII cyanide, while the tautomerized allenyl radicals are trapped by (phen)CuII cyanide (Box= bisoxazoline, phen=phenanthroline). In addition, the reaction features broad substrate scope and excellent functional group compatibility. Moreover, this protocol represents a novel regioselectivity-tunable functionalization of 1,3-enynes via radicals, which we believe will have great implications for the development of catalytic systems for selectivity control in radical and organometallic chemistry.
- Wang, Fei,Wang, Dinghai,Zhou, Yu,Liang, Ling,Lu, Ronghua,Chen, Pinhong,Lin, Zhenyang,Liu, Guosheng
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supporting information
p. 7140 - 7145
(2018/05/29)
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- (Guanidine)copper Complex-Catalyzed Enantioselective Dynamic Kinetic Allylic Alkynylation under Biphasic Condition
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Highly enantioselective allylic alkynylation of racemic bromides under biphasic condition is furnished in this report. This approach employs functionalized terminal alkynes as pro-nucleophiles and provides 6- and 7-membered cyclic 1,4-enynes with high yields and excellent enantioselectivities (up to 96% ee) under mild conditions. Enantioretentive derivatizations highlight the synthetic utility of this transformation. Cold-spray ionization mass spectrometry (CSI-MS) and X-ray crystallography were used to identify some catalytic intermediates, which include guanidinium cuprate ion pairs and a copper-alkynide complex. A linear correlation between the enantiopurity of the catalyst and reaction product indicates the presence of a copper complex bearing a single guanidine ligand at the enantio-determining step. Further experimental and computational studies supported that the alkynylation of allylic bromide underwent an anti-SN2′ pathway catalyzed by nucleophilic cuprate species. Moreover, metal-assisted racemization of allylic bromide allowed the reaction to proceed in a dynamic kinetic fashion to afford the major enantiomer in high yield.
- Cui, Xi-Yang,Ge, Yicen,Tan, Siu Min,Jiang, Huan,Tan, Davin,Lu, Yunpeng,Lee, Richmond,Tan, Choon-Hong
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supporting information
p. 8448 - 8455
(2018/06/22)
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- Cu2O spheres as an efficient source of catalytic Cu(I) species for performing azide-alkyne click reactions
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We report herein the high yield synthesis of Cu2O spheres displaying well-defined shapes and monodisperse sizes that could be employed as the source of highly catalytic active Cu(I) species towards click reactions between several of alkynes and azides to produce a variety of 1,2,3-triazoles under ligand-free and ambient conditions (in an open reactor). The utilization of Cu2O spheres enabled superior performance as compared to a conventional protocol in which CuSO4is employed in combination with sodium ascorbate as the catalyst system. In addition, the compounds were obtained in synthetically useful yields, and seven of them have not been previously reported. We believe the results reported herein shed new insights into the optimization of activity and versatility of click reactions towards the synthesis of target molecules in environmentally friendly conditions.
- Rodrigues, Thenner S.,da Silva, Anderson G.M.,de Oliveira, Lucas C.,da Silva, Adalberto M.,Teixeira, Róbson R.,Camargo, Pedro H.C.
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supporting information
p. 590 - 595
(2017/01/16)
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- Design, Synthesis, and Potency of Pyruvate Dehydrogenase Complex E1 Inhibitors against Cyanobacteria
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Safe and effective algaecides are needed to control agriculturally and environmentally significant algal species. Four series (6, 10, 17, and 21) of 29 novel 4-aminopyrimidine derivatives were rationally designed and synthesized. A part of 10, 17, and 21 displayed potent inhibition of Escherichia coli pyruvate dehydrogenase complex E1 (E. coli PDHc-E1) (IC50 = 2.12-18.06 μM) and good inhibition of Synechocystis sp. PCC 6803 (EC50 = 0.7-7.1 μM) and Microcystis sp. FACH 905 (EC50 = 3.7-7.6 μM). The algaecidal activity of these compounds positively correlated with their inhibition of E. coli PDHc-E1. In particular, 21l and 10b exhibited potent algaecidal activity against PCC 6803 (EC50 = 0.7 and 0.8 μM, respectively), values that were 2-fold increased compared to that of copper sulfate (EC50 = 1.8 μM), and showed the best inhibition of cyanobacterium PDHc-E1 (IC50 = 5.10 and 6.06 μM, respectively). 17h and 21e, the best inhibitors of E. coli PDHc-E1, were studied by molecular docking, site-directed mutagenesis, and enzymatic assays. These results revealed that the improved inhibition of novel inhibitors compared with that of the lead compound I was due to the formation of a new hydrogen bond with Leu264 at the active site of E. coli PDHc-E1. The results proved the great potential to obtain effective algaecides via the rational design of PDHc-E1 inhibitors. [Figure Presented]
- Zhou, Yuan,Feng, Jiangtao,He, Hongwu,Hou, Leifeng,Jiang, Wen,Xie, Dan,Feng, Lingling,Cai, Meng,Peng, Hao
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p. 6491 - 6502
(2017/12/26)
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- Silver-Catalyzed Synthesis of Substituted Pyridine Derivatives from N-Propargylic α-Enamino Esters
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A wide range of substituted pyridine derivatives were synthesized in moderate to good yields from N-propargylic α-enamino esters. The synthetic strategy involved regioselective addition of a propargylamine to the α-carbon atom of an alkynyl ester to produce the N-propargylic α-enamino ester, which acted as the key intermediate in the synthesis.
- Sakthivel, Shanmugam,Sharma, Ashish,Balamurugan, Rengarajan
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supporting information
p. 3941 - 3946
(2017/07/28)
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- Click chemistry approach for the regioselective synthesis of iso-indoline-1,3-dione-linked 1,4 and 1,5 coumarinyl 1,2,3-triazoles and their photophysical properties
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Copper-catalyzed reaction of N-propargyl isoindoline-1,3-dione and 4-azidomethyl coumarins / 4-azidomethyl-1-aza coumarins under click chemistry conditions afforded 1,4-disubstituted 1,2,3-triazoles, whereas ruthenium catalysis yielded isomeric 1,5-disubstituted 1,2,3-triazoles. The two regioisomers have been distinguished by NOE studies. UV absorption for a given pair of isomers exhibited similar trend, whereas fluorescence measurements showed considerable differences. Photo physical studies on the interaction of azides with copper and ruthenium have also been performed.
- Anand, Ashish,Kulkarni, Manohar V.
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p. 722 - 733
(2017/03/27)
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- ALKYNYL PHOSPHINE GOLD COMPLEXES FOR TREATING BACTERIAL INFECTIONS
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A compound of formula (I) for use in the prevention or treatment of a bacterial infection.
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Page/Page column 110
(2017/08/01)
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- 1,4- and 1,5-di(N-phthalimidomethyl)-1,2,3-triazoles: Crystal structures and density functional theory studies of the alkyne and azide precursors
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Two new di(phthalimidomethyl)-1,2,3-triazole derivatives have been synthesised using 1,3-dipolar-cycloadditions under thermal and copper catalysed conditions from N-(azidomethyl)phthalimide and N-prop-2-ynylphthalimide. The molecular structure of both starting materials was studied by X-ray crystallography. A complete DFT analysis of the alkyne and azide compounds was carried out.
- López-González, Ricardo,Bautista-Renedo, Joanatan,Martínez-Otero, Diego,Reyes, Horacio,González-Rivas, Nelly,Cuevas-Ya?ez, Erick
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p. 308 - 313
(2016/07/06)
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- Synthesis of 1,2,3-triazole ‘click’ analogues of thalidomide
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Click analogues of thalidomide were prepared from 3-azidoglutarimide and a diverse array of arylacetylenes and N-ethynyl/N-propargyl phthalimide derivatives. The sequence necessitated a new and scalable synthesis of the key click intermediate 3-azidoglutarimide. The dipolar cycloaddition reactions between the azidoglutarimide and the alkynyl coupling partners utilized a copper sulfate/sodium ascorbate reagent system in aqueous tetrahydrofuran and were first explored using substituted arylalkynes. Along with the click analogues of thalidomide, the click counterparts of the teratogenic and antiangiogenic thalidomide analogue EM-12 were prepared.
- Ronnebaum, Jarrid M.,Luzzio, Frederick A.
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p. 6136 - 6141
(2016/09/14)
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- Synthetic method of N-((2-(1,3-dioxo-dihydroisoindol-2-yl)-propionyl)-5-methoxy)formamide
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The invention discloses a synthetic method of N-(2-(1,3-dioxo-dioxoisoindolin-2-yl)-propionyl)-5-methoxy)formamide. 2-nitro-4-anisidine is taken as an initial raw material, 2-iodine-3-methoxy nitrobenzene is obtained by substitution reaction on a diazonium salt aromatic ring, and then the 2-iodine-3-methoxy nitrobenzene and propargylamine are subjected to Castro-Stephens coupling reaction, reduction reaction and acylation reaction to obtain the N-(2-(1,3-dihydroisoindol-2-yl)-propionyl)-5-methoxy)formamide. Reaction conditions are optimized based on the prior art, and concentrated sulfuric acid replaces concentrated nitric acid; manganese dioxide solid is adopted to catalyze the reaction of propargyl bromide and phthalimide kali salt; manganous-manganic oxide is adopted as a catalyst to catalyze and promote the reaction together with triethylamine, bispalladium chloride and cuprous iodide, the reaction efficiency and yield of a final product are improved, and the industrial production and promotion of the N-(2-(1,3-dioxo-dihydroisoindol-2-yl)-propionyl)-5-methoxy)formamide are facilitated.
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Paragraph 0062; 0063; 0082
(2016/12/01)
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- A phthalimidation protocol that follows protein defined parameters
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This work outlines the first phthalimidation protocol suitable for protein labeling and performed in aqueous media at room temperature and neutral pH with no catalyst or co-reagent required. The methodology is suitable for a range of amines and its efficiency was determined with chemoselective and site-selective protein labeling. This journal is
- Singudas, Rohith,Adusumalli, Srinivasa Rao,Joshi, Pralhad Namdev,Rai, Vishal
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supporting information
p. 473 - 476
(2015/01/09)
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- Synthesis of polyfunctional triethoxysilanes by 'click silylation'
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The copper-catalyzed 'click silylation' has been exploited for the chemical modification of γ-azidopropyltriethoxysilane (AzPTES) with a wide range of terminal alkynes (1a-1v) in a one-pot operation. The novel 1,2,3-triazole-triethoxysilane derivatives (2a-2v) were synthesized by this procedure and comprehensively characterized by IR spectra, 1H and 13C NMR, and HRMS studies.
- Singh, Gurjaspreet,Mangat, Satinderpal Singh,Singh, Jandeep,Arora, Aanchal,Sharma, Ramesh K.
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supporting information
p. 903 - 909
(2015/03/03)
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- Synthesis and evaluation of N-heteroarylsubstituted triazolosulfonamides as carbonic anhydrase inhibitors
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A new series of N-heteroarylsubstituted triazolosulfonamide compounds were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA) I and II were evaluated. Compounds (3 a-k) were prepared by propargylation of N-heteroaryl compounds. Compound 5 was obtained from sulfanilamide and sodium nitrite followed by addition of sodium azide. The products (6 a-k) were synthesized from compounds 3 and 5. The results showed that all the synthesized compounds were inhibited the CA isoenzymes activity. Figure 6a (IC50 = 0.52 μM for hCA I and 0.34 μM for hCA II) has the most inhibitory effect among the synthesized compounds.
- Balci, Ahmet,Arslan, Mustafa,Nixha, Arleta Rifati,Bilen, Cigdem,Ergun, Adem,Gen?er, Nahit
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p. 377 - 382
(2015/07/27)
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- Design and synthesis of novel 2H-chromen-2-one derivatives bearing 1,2,3-triazole moiety as lead antimicrobials
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A series of novel 2H-chromen-2-one derivatives decorated with 1,2,3-triazole moiety were designed and synthesized using the click reaction of azidoalkyloxy-2H-chromen-2-ones with different propargylamines. Propargylamines were obtained by alkylation of various heterocyclic amines with propargyl bromide. Newly synthesized compounds and intermediates were evaluated for their antifungal activity against four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus and Candida albicans). Antibacterial studies were also carried out against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis and Staphylococcus epidermis) and four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Klebsiella pneumoniae). In vitro, bioassay results showed that all the synthesized compounds exhibited excellent activity against fungal strains Aspergillus fumigatus, Aspergillus flavus and Candida albicans. Interestingly, all the compounds have shown even superior activity than the reference drug miconazole against Aspergillus fumigatus. Morpholine and N-acetyl piperazine containing compounds 10c and 10e have shown promising activity against various bacterial strains. Compound 10e was found to be most active against Pseudomonas aeruginosa. Based on, in silico pharmacokinetic studies, compounds 10a-e were identified as lead compounds for future investigation due to their lower toxicity, high drug score values and good oral bioavailability as per OECD guidelines.
- Kushwaha, Khushbu,Kaushik, Nagendra,Lata,Jain, Subhash C.
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supporting information
p. 1795 - 1801
(2014/04/17)
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- Synthesis of polyfunctional triethoxysilanes by 'click silylation'
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The copper-catalyzed 'click silylation' has been exploited for the chemical modification of γ-azidopropyltriethoxysilane (AzPTES) with a wide range of terminal alkynes (1a-1v) in a one-pot operation. The novel 1,2,3-triazole-triethoxysilane derivatives (2a-2v) were synthesized by this procedure and comprehensively characterized by IR spectra, 1H and 13C NMR, and HRMS studies.
- Singh, Gurjaspreet,Mangat, Satinderpal Singh,Singh, Jandeep,Arora, Aanchal,Sharma, Ramesh K.
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supporting information
p. 903 - 909
(2014/02/14)
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- Ultrasound-assisted synthesis of 1-N-β-D-glucopyranosyl-1H-1,2,3- triazole benzoheterocycles and their anti-inflammatory activities
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In this work,the preparation of various glucosyl triazoles from a reaction between 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl azide and terminal alkynes was developed in moderate to excellent yields (63-99percent). Ultrasound energy was applied at each step of the reaction to increase chemical reactivity. In addition,the compounds conjugated with benzoheterocycles moieties revealed potent anti-inflammatory activity.
- Da Silva, Gilson B.,Guimara?es, Bruna M.,Assis, Shalom P. O.,Lima, Vera L. M.,De Oliveira, Ronaldo N.
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p. 914 - 921
(2013/08/23)
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- Palladium-catalyzed trifluoroethylation of terminal alkynes with 1,1,1-trifluoro-2-iodoethane
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An efficient Csp-CH2CF3 bond-forming reaction via Pd-catalyzed 2,2,2-trifluoroethylation of aryl and alkyl terminal alkynes has been developed. This protocol proceeds under mild conditions using the readily available and cheap reagent CF3CH2I as the source of the CH2CF3 group. Various terminal aryl alkynes as well as alkylacetylenes can be transformed into the corresponding trifluoroethylated products in good-to-excellent yields. The method is tolerant of carbonyl, nitro, ester, cyano, and even formyl groups.
- Feng, Yi-Si,Xie, Chuan-Qi,Qiao, Wen-Long,Xu, Hua-Jian
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supporting information
p. 936 - 939
(2013/03/28)
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- Click chemistry from organic halides, diazonium salts and anilines in water catalysed by copper nanoparticles on activated carbon
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An easy-to-prepare, reusable and versatile catalyst consisting of oxidised copper nanoparticles on activated carbon has been fully characterised and found to effectively promote the multicomponent synthesis of 1,2,3-triazoles from organic halides, diazonium salts, and aromatic amines in water at a low copper loading.
- Alonso, Francisco,Moglie, Yanina,Radivoy, Gabriel,Yus, Miguel
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supporting information; experimental part
p. 6385 - 6395
(2011/10/10)
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- A regio- and diastereoselective platinum-catalyzed tandem [2+1]/[3+2] cycloaddition sequence
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Platinum complexes bearing phosphinous acids have efficiently promoted a tandem intermolecular sequence of [2+1]/[3+2] cycloaddition reactions. This process gave access to novel tricyclic systems and the cascade reactions were regio- and diastereoselective (see scheme; Cy=cyclohexyl). The [3+2] cycloaddition reaction was investigated further and two different alkyne partners were used. Copyright
- Achard, Thierry,Lepronier, Aymeric,Gimbert, Yves,Clavier, Herve,Giordano, Laurent,Tenaglia, Alphonse,Buono, Gerard
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supporting information; experimental part
p. 3552 - 3556
(2011/06/09)
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- Synthesis of a new class of triazole-linked benzoheterocycles via 1,3-dipolar cycloaddition
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A new series of 1,2,3-triazole derivatives have been synthesized from phthalimides and terminal alkynes in the presence of a catalytic amount of CuI. The present protocol affords 1,2,3-triazoles in moderate to good yields (44-89percent).
- Barbosa, Fernanda C. G.,De Oliveira, Ronaldo N.
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body text
p. 592 - 597
(2011/10/30)
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- 'Click synthesis' of 1H-1,2,3-triazolyl-based oxiconazole (=(1Z)-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanone O-[(2,4- dichlorophenyl)methyl]oxime) analogs
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The 'click synthesis' of some oxiconazole analogs 5a-5v having 1H-1,2,3-triazolyl residues by Huisgen cycloaddition was achieved in four steps (Scheme 1). Oximation of phenacyl chloride (1) followed by azidation of 2-chloro-1-phenylethanone oxime (2) provided azido ketoxime 3. The CuI-catalyzed Huisgen cycloaddition of 3 with terminal alkynes gave the 4-substituted (at the triazole) 2-(1H-1,2,3-triazol-1-yl)-1-phenylethanone oximes 4a-4i. The O-alkylation of 4a-4i with various alkyl halides resulted in the formation of the target molecules 5a-5v in good yields. Copyright
- Soltani Rad, Mohammad Navid,Asrari, Zeinab,Behrouz, Somayeh,Hakimelahi, Gholam Hossein,Khalafi-Nezhad, Ali
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experimental part
p. 2194 - 2206
(2012/01/31)
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- Gold-catalyzed transformation of 2-alkynyl arylazides: Efficient access to the valuable pseudoindoxyl and indolyl frameworks
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An element of surprise: A series of functionalized 2-alkynyl arylazides has beed converted into 3-substituted indoles or 2,2-disubstituted indolin-3-ones in the presence of a gold(I) complex. Various oxygen or aryl nucleophiles can be used in this process to trap the intermediate α-imino gold carbene. The structural motifs of the products are found in a large variety of biologically active compounds and natural products. Copyright
- Wetzel, Alexander,Gagosz, Fabien
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supporting information; experimental part
p. 7354 - 7358
(2011/09/16)
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- Design of reaction media for nucleophilic substitution reactions by using a catalytic amount of an amphiphilic imidazolium salt in water
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Molecules of an amphiphilic imidazolium salt assemble in water to form a hydrophobic membrane including an interface consisting of ammonium species. Such an interface works as a reaction medium like an ionic liquid. We used the medium for nucleophilic substitution reactions between alkyl halides and anionic nucleophiles. This procedure allowed the reactions to proceed efficiently in water without any organic solvent.
- Asano, Keisuke,Matsubara, Seijiro
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experimental part
p. 989 - 1002
(2010/10/19)
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- ALKOXY COMPOUNDS FOR DISEASE TREATMENT
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The present invention relates generally to compositions and methods for treating neurodegenerative diseases and disorders, particularly ophthalmic diseases and disorders. Provided herein are alkoxyl derivative compounds and pharmaceutical compositions comprising these compounds. The subject compositions are useful for treating and preventing ophthalmic diseases and disorders, including age-related macular degeneration (AMD) and Stargardt's Disease.
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Page/Page column 145-146
(2009/05/29)
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- Platinum(II) alkynyl complexes containing N- and S-propargylated ligands: Synthesis, structures and formation of PtII/AgI coordination compounds
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Alkylation of 2-hydroxypyridine, 2-pyridinethiol, 2-hydroxy-4- methylquinoline, phthalimide and pyrazole with propargyl bromide gave a series of alkynes in high yield. These alkynes were reacted with the chloroplatinum(II) compounds trans-[PtCl2(PPh3)2] and cis-[PtCl2(dppe)] to afford the respective trans- and cis-bis(alkynyl)platinum(II) complexes, which were characterised by spectroscopic analysis and by X-ray diffraction. The platinum(II) complexes containing the thiopyridyl- and pyrazolyl-substituted alkynes react with 1 or 2 equiv. of [Ag(NO3)(PPh3)] to give dimetallic Pt II/AgI complexes. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Mohr, Fabian,Mendia, Aranzazu,Laguna, Mariano
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p. 3115 - 3123
(2008/02/13)
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- Immunologically driven antibodies chemical engineering: Design and synthesis of a hapten aimed at nerve agent hydrolysis
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In this letter, we describe the design and the synthesis of an organophosphorus hapten aimed at a mixed biotechnological-chemical strategy for the mild decontamination of exceedingly toxic nerve agent VX. Hapten will be used to raise and select monoclonal antibodies (mAbs) able to bind both the nerve agent, and an oxime, derived from pyridinaldoxime, able to specifically hydrolyze its P-S bond. In order to significantly increase the hydrolysis reaction rate, the controlled respective positioning of the oxime and of the substrate will be achieved through the immunization, and in a second step, the oxime will be bound to the mAb in a reactive position towards the reactive thiophosphate functionality of the substrate.
- Jovic, Florence,Louise, Ludivine,Mioskowski, Charles,Renard, Pierre-Yves
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p. 6809 - 6814
(2007/10/03)
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- Facile synthesis of α,β-acetylenic ketones and 2,5-disubstituted furans: Consecutive activation of triple and double bond with ZnBr2 toward the synthesis of furan ring
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α,β-Acetylenic ketones were synthesized from the reaction of acid chlorides and acetylenic compounds in the presence of ZnBr2 and DIEA in acetonitrile. From the acetylenic ketones having nearby methylene unit, 2,5-disubstituted furan derivatives could be synthesized under the same reaction conditions.
- Lee, Ka Young,Lee, Mi Jung,Kim, Jae Nyoung
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p. 8705 - 8710
(2007/10/03)
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