- Synthesis of calix[4]pyrrole-based acrylate and acrylamide monomers: Precursors for preparation of anion-selective polymer membranes
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Octamethylcalix[4]pyrrole derivatives with hydroxy alkyl and amino alkyl side chains were prepared and converted into the corresponding acrylate and acrylamide derivatives, respectively. Georg Thieme Verlag Stuttgart.
- Zyryanov, Grigory V.,Kinstle, Thomas H.,Anzenbacher Jr., Pavel
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Read Online
- Thienopyrimidinone Based Sirtuin-2 (SIRT2)-Selective Inhibitors Bind in the Ligand Induced Selectivity Pocket
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Sirtuins (SIRTs) are NAD-dependent deacylases, known to be involved in a variety of pathophysiological processes and thus remain promising therapeutic targets for further validation. Previously, we reported a novel thienopyrimidinone SIRT2 inhibitor with good potency and excellent selectivity for SIRT2. Herein, we report an extensive SAR study of this chemical series and identify the key pharmacophoric elements and physiochemical properties that underpin the excellent activity observed. New analogues have been identified with submicromolar SIRT2 inhibtory activity and good to excellent SIRT2 subtype-selectivity. Importantly, we report a cocrystal structure of one of our compounds (29c) bound to SIRT2. This reveals our series to induce the formation of a previously reported selectivity pocket but to bind in an inverted fashion to what might be intuitively expected. We believe these findings will contribute significantly to an understanding of the mechanism of action of SIRT2 inhibitors and to the identification of refined, second generation inhibitors.
- Sundriyal, Sandeep,Moniot, Sébastien,Mahmud, Zimam,Yao, Shang,Di Fruscia, Paolo,Reynolds, Christopher R.,Dexter, David T.,Sternberg, Michael J. E.,Lam, Eric W.-F.,Steegborn, Clemens,Fuchter, Matthew J.
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Read Online
- Gold N-Heterocyclic Carbene Catalysts for the Hydrofluorination of Alkynes Using Hydrofluoric Acid: Reaction Scope, Mechanistic Studies and the Tracking of Elusive Intermediates
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An efficient and chemoselective methodology deploying gold-N-heterocyclic carbene (NHC) complexes as catalysts in the hydrofluorination of terminal alkynes using aqueous HF has been developed. Mechanistic studies shed light on an in situ generated catalyst, formed by the reaction of Br?nsted basic gold pre-catalysts with HF in water, which exhibits the highest reactivity and chemoselectivity. The catalytic system has a wide alkyl substituted-substrate scope, and stoichiometric as well as catalytic reactions with tailor-designed gold pre-catalysts enable the identification of various gold species involved along the catalytic cycle. Computational studies aid in understanding the chemoselectivity observed through examination of key mechanistic steps for phosphine- and NHC-coordinated gold species bearing the triflate counterion and the elusive key complex bearing a bifluoride counterion.
- Bédard, Sandrine,Cavallo, Luigi,Falivene, Laura,Gauthier, Rapha?l,Nolan, Steven P.,Paquin, Jean-Fran?ois,Saab, Marina,Tzouras, Nikolaos V.,Van Hecke, Kristof,Zhang, Ziyun
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supporting information
(2021/12/09)
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- 5-phenoxy primaquine analogs and the tetraoxane hybrid as antimalarial agents
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The rapid emergence of drug resistance to the current antimalarial agents has led to the urgent need for the discovery of new and effective compounds. In this work, a series of 5-phenoxy primaquine analogs with 8-aminoquinoline core (7a–7h) was synthesize
- Jansongsaeng, Somruedee,Kamchonwongpaisan, Sumalee,Khotavivattana, Tanatorn,Pengon, Jutharat,Srimongkolpithak, Nitipol
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- Synthesis method of 2-methyl pyrroline
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The invention discloses a synthesis method of 2-methyl pyrroline. The preparation method comprises the following steps: adding valeryl chloride and phthaloyl potassium salt into a high-boiling-point solvent and carrying out heating reflux for 5 to 15 hours; and S2, after the reaction liquid is cooled, filtering the reaction liquid, concentrating the reaction liquid, adding methanol for pulping toobtain a crude product, adding the crude product obtained in S1 into hydrochloric acid for heating reflux, after the reaction is completed, performing concentrating to dryness, adding water into residual liquid for dissolving, adjusting the pH value to be about 11 by using sodium carbonate, performing extracting for 3-5 times by using dichloromethane, and performing concentrating and drying, and distilling to obtain a product. According to the synthetic method of the 2-methyl pyrroline, disclosed by the invention, the used initial raw materials are easy to obtain, the preparation is convenient, the enlarged production is easy, the intermediate product is stable, and the collection efficiency is high.
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Paragraph 0014; 0016-0017
(2020/06/16)
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- Substituted imidazo[4,5-c]quinoline macrocyclic compound as multi-target kinase inhibitor
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The invention discloses a substituted imidazo[4,5-c]quinoline macrocyclic compound as a multi-target kinase inhibitor, and relates to a compound represented by a formula (I) or a pharmaceutically acceptable salt, a solvate, a polymorphic substance or an isomer thereof, and applications of the compound in preparation of a medicine for treating ALK-mediated diseases.
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Paragraph 0128-0131
(2020/04/17)
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- Tuning Regioselectivity of Wacker Oxidation in One Catalytic System: Small Change Makes Big Step
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A regioselectivity switchable aerobic Wacker-Tsuji oxidation has been developed using catalytic tert-butyl nitrite as a simple organic redox cocatalyst. By solely switching the solvent, either substituted aldehydes or ketones could be prepared under mild
- Hu, Kang-Fei,Ning, Xiao-Shan,Qu, Jian-Ping,Kang, Yan-Biao
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p. 11327 - 11332
(2018/09/06)
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- The gold-catalyzed formal hydration, decarboxylation, and [4+2] cycloaddition of alkyne derivatives featuring L2/Z-type diphosphinoborane ligands
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The catalytic formal hydration of alkynes and decarbox-ylation of alkynoic acid were developed using a Au catalyst featuring a Z-ligand. Furthermore, the intramolecular [4+2] cycloaddition of the alkynoic acid-alkene derivative for the formation of the oxabicyclo[4.4.0] skeleton also proceeded.
- Matsumoto, Chiaki,Yamada, Masayuki,Dong, Xun,Mukai, Chisato,Inagaki, Fuyuhiko
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supporting information
p. 1321 - 1323
(2018/10/15)
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- Palladium-catalysed anti-Markovnikov selective oxidative amination
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In recent years, the synthesis of amines and other nitrogen-containing motifs has been a major area of research in organic chemistry because they are widely represented in biologically active molecules. Current strategies rely on a multistep approach and require one reactant to be activated prior to the carbon-nitrogen bond formation. This leads to a reaction inefficiency and functional group intolerance. As such, a general approach to the synthesis of nitrogen-containing compounds from readily available and benign starting materials is highly desirable. Here we present a palladium-catalysed oxidative amination reaction in which the addition of the nitrogen occurs at the less-substituted carbon of a double bond, in what is known as anti-Markovnikov selectivity. Alkenes are shown to react with imides in the presence of a palladate catalyst to generate the terminal imide through trans-aminopalladation. Subsequently, olefin isomerization occurs to afford the thermodynamically favoured products. Both the scope of the transformation and mechanistic investigations are reported.
- Kohler, Daniel G.,Gockel, Samuel N.,Kennemur, Jennifer L.,Waller, Peter J.,Hull, Kami L.
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p. 333 - 340
(2018/02/27)
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- Tuning Selectivity in Aliphatic C-H Bond Oxidation of N-Alkylamides and Phthalimides Catalyzed by Manganese Complexes
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Site selective C-H oxidation of N-alkylamides and phthalimides with aqueous hydrogen peroxide catalyzed by manganese complexes is described. These catalysts are shown to exhibit substantially improved performance in product yields and substrate scope in comparison with their iron counterparts. The nature of the amide and imide group and of the N-alkyl moiety are shown to be effective tools in order to finely tune site selectivity between proximal (adjacent to the nitrogen) and remote C-H bonds on the basis of steric, electronic, and stereoelectronic effects. Moreover, formation of the α-hydroxyalkyl product in good yield and with excellent product chemoselectivity was observed in the reactions of the pivalamide and acetamide derivatives bearing an α-CH2 group, pointing again toward an important role played by stereoelectronic effects and supporting the hypothesis that these oxidations proceed via hydrogen atom transfer (HAT) to a high-valent manganese-oxo species. Good product yields and mass balances are obtained in short reaction times and under mild experimental conditions when relatively low loadings of an electron-rich manganese catalyst are used. The potential utility of these reactions for preparative purposes is highlighted in the site-selective oxidation of the pivalamide and phthalimide derivatives of substrates of pharmaceutical interest.
- Milan, Michela,Carboni, Giulia,Salamone, Michela,Costas, Miquel,Bietti, Massimo
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p. 5903 - 5911
(2017/09/15)
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- Oxidation of Secondary Methyl Ethers to Ketones
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We present a mild way of converting secondary methyl ethers into ketones using calcium hypochlorite in aqueous acetonitrile with acetic acid as activator. The reaction is compatible with various oxygen- and nitrogen-containing functional groups and afforded the corresponding ketones in up to 98% yield. The use of this methodology could expand the application of the methyl group as a useful protecting group.
- Gilissen, Pieter J.,Blanco-Ania, Daniel,Rutjes, Floris P. J. T.
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p. 6671 - 6679
(2017/07/15)
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- Synthesis and functional characterization of imbutamine analogs as histamine H3 and H4 receptor ligands
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Imbutamine (4-(1H-imidazol-4-yl)butanamine) is a potent histamine H 3 (H3R) and H4 receptor (H4R) agonist (EC50 values: 3 and 66 nM, respectively). Aiming at improved selectivity for the H4R, the imidazole ring in imbutamine was methyl-substituted or replaced by various differently substituted heterocycles (1,2,3-triazoles, 1,2,4-triazoles, pyridines, pyrimidines) as potential bioisosteres. Investigations in [35S]GTPγS binding assays using membranes of Sf9 insect cells expressing the respective human histamine receptor subtype revealed only very weak activity of most of the synthesized hetarylalkylamines at both receptors. By contrast, the introduction of substituents at the 4-imidazolyl ring was most effective regarding H 4R selectivity. This holds for methyl substitution in position 2 and, especially, in position 5. 5-Methylimbutamine (H4R: EC50 = 59 nM, α = 0.8) was equipotent with imbutamine at the hH4R, but revealed about 16-fold selectivity for the hH4R compared to the hH3R (EC50 980 nM, α = 0.36), whereas imbutamine preferred the hH3R. The functional activities were in agreement with radioligand binding data. The results support the hypothesis that, by analogy with histamine, methyl substitution in histamine homologs offers a way to shift the selectivity in favor of the H4R. According to a bioisosteric approach, the imidazole ring in the dual histamine H3/H4 receptor agonist imbutamine (n = 4) was replaced by various five- and six-membered N-heterocycles. Whereas these structural modifications resulted in a reduction or loss of activity at both receptors, 5-methyl substitution at the imidazol-4-yl ring in imbutamine changed the receptor subtype selectivity in favor of the H4R.
- Geyer, Roland,Kaske, Melanie,Baumeister, Paul,Buschauer, Armin
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- gem-difluorination of aminoalkynes via highly reactive dicationic species in superacid HF-SbF5: Application to the efficient synthesis of difluorinated cinchona alkaloid derivatives
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(Chemical Equation Presented) A variety of alkynylated amines, amides, and imides are reacted in the superacid system HF-SbF5 to give regioselectively new β-gem-difluoroamines. The reaction, which is not observed in pure HF, is consistent with
- Cantet, Anne-Celine,Carreyre, Helene,Gesson, Jean-Pierre,Jouannetaud, Marie-Paule,Renoux, Brigitte
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p. 2875 - 2878
(2008/09/19)
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- PROCESS FOR THE PREPARATION OF QUINOLINE DERIVATIVES
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The invention relates to a process for the preparation of certain quinoline derivatives, in particular, 8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5-(3-trifluoromethylphenoxy)quinoline succinate.
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Page/Page column 7
(2010/02/07)
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- Inhibitors or bone reabsorption and antagonists of vitronectin receptors
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Novel inhibitors of bone reabsorption and antagonists of vitronectin receptors The present invention relates to 5-membered ring heterocycles of the formula I, in which E, F, G, W, Y and Z have the meaning given in the patent claims, to their preparation a
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- New serotonin 5-HT1F agonists
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This invention provides novel 5-HT1Fagonists of formula where X, Y, Z,and R are defined in the specification, which are useful for the prevention and treatment of migraine and associated disorders.
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- Silyl Enol Ethers in Paterno-Buechi Reactions. Functional Group Tolerance and the Effect of β-Alkyl Substitution
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The photochemically induced diastereoselective formation of 3-(silyloxy)oxetanes from silyl enol ethers and aromatic aldehydes was studied.It is shown that many heteroatom- and double bond-containing substituents (ether, ester, acetal, amide, alkene) withstand the reaction conditions and may therefore be attached either to the carbonyl compound (e.g. 9) or to the silyl enol ether (e.g. 1).The formation of several functionalized oxetanes such as 2 and 11 was achieved in decent yields (42-70percent).Furthermore the effect of β-substituents at the silyl enol ether was investigated.A stereoconvergent Paterno-Buechi reaction of aromatic aldehydes afforded the corresponding oxetanes (13, 16-18) in fair to excellent yields (45-87percent) and with diastereoselectivities (ds) of 65-95percent.No detrimental influence of the steric bulk in the β-position (R1 = Me, Et, and iPr) on the regiochemistry of the reaction was observed.Large substituents in the α-position of the enol ether proved beneficial, isolated yields of the major diastereoisomeric oxetane ranging between 60 and 87percent.The configuration of the products was elucidated by 1H-NMR spectroscopy.In the major isomer all large vicinal substituents Ar (at C-2), R (at C-3), and R1 (at C-4) at the oxetane nucleus are oriented trans to each other.The stereoselective formation of three stereogenic centers at a time can be explained by a non-concerted mechanism which invokes the intermediacy of 1,4-diradicals as intermediates. - Key Words: Paterno-Buechi reaction / Oxetanes / Diastereoselectivity / Silyl enol ethers / Photocycloaddition
- Bach, Thorsten
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p. 855 - 866
(2007/10/02)
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- Triazolo[4,5-f]quinolines. Part VI. Synthesis and evaluation of 9-aminoalkyl(aryl)-2-methyl-2H-[4,5-f]quinolines as anticancer agents. Preliminary results of in vitro screening
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9-Aminoalkyl(aryl)-2-methyl-2H-triazolo[4,5-f]quinolines were prepared in order to evaluate their in vitro antitumor activity. Some members of this series exbibited both cell selectivity and tumor growth inhibition activity at concentrations between 10su
- Sanna,Sequi,Pagletti
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- COMPOUNDS AND PROCESS PREPARING A SUBSTITUTED OR AN UNSUBSTITUTED 4(5)-(OMEGA-AMINOALKYL)IMIDAZOLE
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A process is provided for preparing novel substituted or unsubstituted 4(5)-ω-aminoalkyl)imidazoles of the formula STR1 wherein n is 1 to 6, R 1 is hydrogen or a linear, branched or cyclic, saturated or unsaturated alkyl group having 1-6 C-atoms or a phenyl ring being unsubstituted, or mono-or di-substituted with groups such as lower alkyl, halogen, alkoxy, methylenedioxy or a combination thereof, and R. sub.2 is hydrogen or methyl. The process comprises brominating an ω-phthalimidoalkan-2-one with bromine in anhydrous methanol to a 1-or 3-bromo-ω-phthalimido-alkan-2-one, subjecting said derivative to ring closure with an amidine in N.N-dimethylformamide with potassium carbonate under mild conditions followed by hydrolytic separation of the phthalic residue. Pharmaceutical compounds, compositions and a method of treatment are also provided.
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- Histamine H2-receptor agonists. Synthesis, in vitro pharmacology, and qualitative structure-activity relationships of substituted 4- and 5-(2- aminoethyl)thiazoles
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It is well known that both histamine and dimaprit show moderate histamine H2-receptor agonistic activities on the guinea pig right atrium. Quantum chemical calculations on these two compounds showed similarities in electron distributions and molecular electrostatic potentials (MEP's), which could be extended to rigid analogues [2-amino-5-(2-aminoethyl)thiazoles] of the latter structure. On the base of these results a series of substituted 4- and 5-(2- aminoethyl)thiazoles was synthesized applying small alkyl substitution variations as reported for histamine. 2-Amino-5-(2-aminoethyl)-4- methylthiazole (Amthamine) proved to be the most potent full histamine H2- receptor agonist on the guinea pig right atrium, being with a pD2 value of 6.21 slightly more potent than histamine. This compound shows no affinity for H1-receptors and is a full but weak agonist on the histamine H3-receptor with a pD2 value of 4.70, thus showing a marked specificity for histamine H2-receptors. In the 5-(2-aminoethyl)thiazole series the presence of a 2- amino substituent proved to be not essential for stimulation of the histamine H2-receptor, leading to the important conclusion that in contrast to histamine, for this series, acceptance of a proton by the thiazole nucleus of the agonist from the active site of the receptor is sufficient for the stimulation of the histamine H2-receptor.
- Eriks,Van der Goot,Sterk,Timmerman
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p. 3239 - 3246
(2007/10/02)
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- An Alternative Synthesis of Homohistamine and Structurally Related (Imidazole-4-yl)alkylamines
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Bromination of N-(4-oxopentyl)phthalimide (3) leads to isomeric bromoketones 2a and 2e, which undergo cyclisation with formamidine in liquid ammonia to yield homohistamine (1a) and 5-methylhistamine (1e).Similarly racemic α-methyl- (1b) and 2-methylhomohistamine (1c) are synthesized.The resolution of 1b is achieved using (+)- and (-)-di-O-(4-toluoyl)tartaric acid. 1 are intermediates in the synthesis of impromidine like, H2-histaminergic compounds. - Key words: Bromination of Methylketones, Halomethylketones, Histamine H2-Agonists, Homohistamine, Chiral Aminoalkylimidazoles
- Elz, Sigurd,Schunack, Walter
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p. 238 - 242
(2007/10/02)
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