- Method for catalyzing hydrodesulfurization of thioamide derivative
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The invention provides a method for catalyzing hydrodesulfurization of a thioamide derivative, which comprises the following steps: sequentially adding a pentacarbonyl manganese bromide catalyst, a reaction substrate thioamide derivative, Lewis acid, a solvent and alkali into a polytetrafluoroethylene lined reaction tube, putting the reaction tube into a high-pressure kettle, introducing hydrogen to carry out catalytic hydrogenation reaction, cooling to room temperature, discharging gas, washing the reaction tube with ethyl acetate, passing through a silica gel small short column, carrying out spin drying, and carrying out column chromatography purification to obtain a target product. The monovalent manganese which is low in toxicity and good in chemical selectivity and biocompatibility is used as the catalyst to catalyze hydrodesulfurization of the thioamide derivative, the substrate range is wide, the yield of amine is high, and the method has high drug synthesis application value.
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Paragraph 0034-0038
(2021/07/09)
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- Iodine-Mediated Coupling of Cyclic Amines with Sulfonyl Hydrazides: an Efficient Synthesis of Vinyl Sulfone Derivatives
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An efficient iodine-mediated coupling of cyclic amines with sulfonyl hydrazides is reported. This transformation opens a new route to the synthesis of vinyl sulfones derivatives, which is a common structural motif in natural products and pharmaceuticals. Tentative mechanistic studies suggest that this reaction is likely to involve a radical process.
- Rong, Xiaona,Guo, Jingwen,Hu, Zheqi,Huang, Lehao,Gu, Yugui,Cai, Yuepiao,Liang, Guang,Xia, Qinqin
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supporting information
p. 701 - 708
(2020/12/30)
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- Synthesis of tertiary amines by direct Br?nsted acid catalyzed reductive amination
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Tertiary amines are ubiquitous and valuable compounds in synthetic chemistry, with a wide range of applications in organocatalysis, organometallic complexes, biological processes and pharmaceutical chemistry. One of the most frequently used pathways to synthesize tertiary amines is the reductive amination reaction of carbonyl compounds. Despite developments of numerous new reductive amination methods in the past few decades, this reaction generally requires non-atom-economic processes with harsh conditions and toxic transition-metal catalysts. Herein, we report simple yet practical protocols using triflic acid as a catalyst to efficiently promote the direct reductive amination reactions of carbonyl compounds on a broad range of substrates. Applications of this new method to generate valuable heterocyclic frameworks and polyamines are also included.
- Hussein, Mohanad A.,Dinh, An H.,Huynh, Vien T.,Nguyen, Thanh Vinh
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supporting information
p. 8691 - 8694
(2020/08/21)
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- Iron-Catalysed Reductive Amination of Carbonyl Derivatives with Ω-Amino Fatty Acids to Access Cyclic Amines
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An efficient method for the reductive amination of carbonyl derivatives with ω-amino fatty acids catalysed by an iron complex Fe(CO)4(IMes) [IMes=1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene] by means of hydrosilylation was developed. A variety of pyrrolidines, piperidines and azepanes were selectively synthesised in moderate-to-excellent yields (36 examples, 47–97 % isolated yield) with a good functional group tolerance.
- Wei, Duo,Netkaew, Chakkrit,Carré, Victor,Darcel, Christophe
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p. 3008 - 3012
(2019/05/15)
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- Chemoselective amide reductions by heteroleptic fluoroaryl boron Lewis acids
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The heteroleptic borane catalyst (C6F5)2B(CH2CH2CH2)BPin is found to hydrosilylatively reduce amides under mild conditions. Simple tertiary amides can be reduced using Me2EtSiH, whereas tertiary benzamides required a more reactive secondary silane, Et2SiH2, for efficient reduction. The catalytic system described exhibits exceptional chemoselectivity in the reduction of oligoamides and tolerates functionalities which are prone to reduction under similar conditions.
- Peruzzi, Michael T.,Mei, Qiong Qiong,Lee, Stephen J.,Gagné, Michel R.
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p. 5855 - 5858
(2018/06/13)
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- Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
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Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.
- Taylor, Nicholas J.,Emer, Enrico,Preshlock, Sean,Schedler, Michael,Tredwell, Matthew,Verhoog, Stefan,Mercier, Joel,Genicot, Christophe,Gouverneur, Véronique
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supporting information
p. 8267 - 8276
(2017/06/27)
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- Structure-based optimization leads to the discovery of NSC765844, a highly potent, less toxic and orally efficacious dual PI3K/mTOR inhibitor
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The phosphoinositide 3-kinase (PI3K) family is one of the most frequently activated enzymes in a wide range of human cancers; thus, inhibition of PI3K represents a promising strategy for cancer therapy. Herein, a series of benzylamine substituted arylsulfonamides were designed and synthesized as dual PI3K/mTOR inhibitors using a strategy integrating focused library design and virtual screening, resulting in the discovery of 13b (NSC765844). The compound 13b exhibits highly potent enzyme inhibition with IC50s of 1.3, 1.8, 1.5, 3.8 and 3.8?nM for PI3Kα, β, γ, δ, and mTOR, respectively. 13b was further evaluated in NCI by an in?vitro cytotoxic screening program. Broad-spectrum antitumor activities with mean GI50value of 18.6?nM against approximately 60 human tumor cell lines were found. 13b displayed favorable physicochemical properties and superior pharmacokinetic profiles for animal studies. It significantly inhibited tumor growth when administered orally in an A549 non-small-cell lung carcinoma xenograft and BEL7404 human hepatocellular carcinoma xenograft models. On the basis of its excellent in?vivo efficacy and superior pharmacokinetic profiles, 13b has been selected for further preclinical investigation as a promising anticancer drug candidate.
- Han, Jinsong,Chen, Ying,Yang, Chao,Liu, Ting,Wang, Mingping,Xu, Haojie,Zhang, Ling,Zheng, Canhui,Song, Yunlong,Zhu, Ju
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p. 684 - 701
(2016/07/21)
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- Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes: Versatile Catalysts for Hydrosilylation Reactions
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NHC-rhodium complexes (NHC=N-heterocyclic carbenes) have been widely used as efficient catalysts for hydrosilylation reactions. However, the substrates were mostly limited to reactive carbonyl compounds (aldehydes and ketones) or carbon-carbon multiple bonds. Here, we describe the application of newly-developed chelating bis(tzNHC)-rhodium complexes (tz=1,2,3-triazol-5-ylidene) for several reductive transformations. With these catalysts, the formal reductive methylation of amines using carbon dioxide, the hydrosilylation of amides and carboxylic acids, and the reductive alkylation of amines using carboxylic acids have been achieved under mild reaction conditions.
- Nguyen, Thanh V. Q.,Yoo, Woo-Jin,Kobayashi, Shu
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p. 452 - 458
(2016/02/12)
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- Novel Potent Proline-Based Metalloproteinase Inhibitors: Design, (Radio)Synthesis, and First in Vivo Evaluation as Radiotracers for Positron Emission Tomography
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As dysregulation of matrix metalloproteinase (MMP) activity is associated with a wide range of pathophysiological processes like cancer, atherosclerosis, and arthritis, MMPs represent a valuable target for the development of new therapeutics and diagnostic tools. We herein present the chiral pool syntheses, in vitro evaluation, and SAR studies of a series of d- and l-proline- as well as of (4R)-4-hydroxy-l-proline-derived MMP inhibitors possessing general formula 1. Some of the synthesized hydroxamic acids were found to be potent MMP inhibitors with IC50 values in the nanomolar range, also demonstrating no off-target effects toward the other tested Zn2+-dependent metalloproteases (ADAMs and meprins). Utilizing the structure of the (2S,4S)-configured 4-hydroxyproline derivative 4, a selective picomolar inhibitor of MMP-13, the radiolabeled counterpart [18F]4 was successfully synthesized. The radiotracer's biodistribution in mice as well as its serum stability were evaluated for assessing its potential use as a MMP-13 targeting PET imaging agent.
- Kalinin, Dmitrii V.,Wagner, Stefan,Riemann, Burkhard,Hermann, Sven,Schmidt, Frederike,Becker-Pauly, Christoph,Rose-John, Stefan,Sch?fers, Michael,Holl, Ralph
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supporting information
p. 9541 - 9559
(2016/11/11)
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- Mild and selective Et2Zn-catalyzed reduction of tertiary amides under Hydrosilylation conditions
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Diethylzinc (Et2Zn) can be used as an efficient and chemoselective catalyst for the reduction of tertiary amides under mild reaction conditions employing cost-effective polymeric silane (PMHS) as the hydride source. Crucial for the catalytic activity was the addition of a substoichiometric amount of lithium chloride to the reaction mixture. A series of amides containing different additional functional groups were reduced to their corresponding amines, and the products were isolated in good-to-excellent yields.
- Kovalenko, Oleksandr O.,Volkov, Alexey,Adolfsson, Hans
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p. 446 - 449
(2015/03/05)
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- Highly efficient and eco-friendly synthesis of tertiary amines by reductive alkylation of aldehydes with secondary amines over a Pt nanowires catalyst
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Plentiful tertiary amine derivates are synthesized by direct formation of tertiary amines by the interaction of aldehydes with secondary amines over Pt nanowires under mild conditions. This method offers a green and rapid approach to transform secondary amines into various tertiary amines.
- Wu, Junjie,Lu, Shuanglong,Ge, Danhua,Gu, Hongwei
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p. 81395 - 81398
(2015/10/06)
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- Interfacial hydrogenation and deamination of nitriles to selectively synthesize tertiary amines
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A novel one-pot method has been developed for the interfacial hydrogenation of nitriles to synthesize asymmetrical tertiary amines. The active Pt NWs allow for the preparation of a series of tertiary amines in excellent yields (up to 99.0%) and a mixed solvent is vital for the adjustment of the yield. And also, the reaction proceeded under mild conditions and is environmentally friendly.
- Lu, Shuanglong,Li, Chao,Wang, Jiaqing,Pan, Yue,Cao, Xueqing,Gu, Hongwei
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supporting information
p. 11110 - 11113
(2014/10/15)
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- Iridium-catalyzed decarboxylative N-alkylation of α-amino acids with primary alcohols
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A new decarboxylative N-alkylation reaction of α-amino acids has been developed. A variety of tertiary amines were obtained in good to excellent yields via the decarboxylative N-alkylation reaction of α-amino acids with primary alcohols catalyzed by a CpIr complex. Georg Thieme Verlag Stuttgart New York.
- Wu, Jiashou,Jiang, Huajiang,Chen, Dingben,Shen, Jianfen,Zhao, Datong,Xiang, Jing,Zhou, Qizhong
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p. 539 - 542
(2014/03/21)
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- Reusable supported ruthenium catalysts for the alkylation of amines by using primary alcohols
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Efficient and recyclable ruthenium catalysts were synthesized from readily available polystyrene-or silica-supported phosphine ligands. Catalysts bound to the polymer support through an ether linkage showed good to excellent activity towards the N-alkylation of primary and secondary amines to afford the alkylated products in 62-99 % yield at 120-140°C. The supported phosphine ligand/ruthenium ratio was found to be crucial for higher catalytic activity and lower ruthenium leaching. The continuous flow N-alkylation of amines was demonstrated by using the supported catalyst in a column reactor. By adopting the hydrogen-borrowing strategy, the synthesis of the anti-Parkinson agent Piribedil was established in 98 % yield at 140°C. Support group steals the show: An efficient Ru-based heterogeneous catalyst from readily available supported phosphine ligands is developed. The nature of the linkage and the extent of ruthenium incorporation are crucial in determining the catalytic activity. The catalyst can be recycled and used under continuous flow in a packed-bed reactor. The alkylation of cyclic amines is achieved in excellent yield at moderate temperatures in the absence of any external base.
- Peishan, Siah,Dang, Tuan Thanh,Seayad, Abdul Majeed,Ramalingam, Balamurugan
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p. 808 - 814
(2014/03/21)
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- Triol-promoted activation of C-F bonds: Amination of benzylic fluorides under highly concentrated conditions mediated by 1,1,1-tris(hydroxymethyl) propane
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Activation of the C-F bond of benzylic fluorides was achieved using 1,1,1-tris(hydroxymethyl)propane (2) as a hydrogen bonddonating agent. Investigations demonstrated that hydrogen bond-donating solvents are promoting the activation and hydrogen bondaccepting ones are hindering it. However, the reaction is best run under highly concentrated conditions, where solvents cannot interfere with the interaction between the organofluorine compound and the triol. Various benzylic fluorides react with secondary amines or anilines to form benzylic amines in good yields.
- Champagne, Pier Alexandre,Saint-Martin, Alexandre,Drouin, Melina,Paquin, Jean-Francois
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supporting information
p. 2451 - 2456
(2014/01/06)
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- Facile and efficient KOH-catalysed reduction of esters and tertiary amides
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Esters and tertiary amides were efficiently reduced to their corresponding alcohols and amines in high yields under mild and environmentally friendly conditions. The presented KOH-catalysed system involves a simple hydrosilylation procedure that is carried out under solvent-free conditions and does not require the use of inert conditions.
- Fernandez-Salas, Jose A.,Manzini, Simone,Nolan, Steven P.
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p. 9758 - 9760
(2013/10/21)
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- Direct hydrosilylation of tertiary amides to amines by an in situ formed iron/N-heterocyclic carbene catalyst
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Tertiary amides were efficiently reduced to their corresponding tertiary amines in high isolated yields by using the commercially available and inexpensive polymeric silane polymethylhydrosiloxane (PMHS) as the reducing agent. The reaction is efficiently catalyzed by an in situ generated iron/N-heterocyclic carbene complex (1 mol-%) obtained from iron(II) acetate and 1-(2-hydroxy-2-phenylethyl)-3-methylimidazolium triflate ([PhHEMIM][OTF]). A catalytic amount of lithium chloride (1 mol-%) present in the reaction mixture significantly reduced the reaction time and increased the chemoselectivity of the reduction process. Tertiary amides are reduced to their corresponding tertiary amines in high isolated yields by using the polymeric silane polymethylhydrosiloxane (PMHS) in the presence of an in situ generated iron/N-heterocyclic carbene complex (1 mol-%), generated from iron(II) acetate and 1-(2-hydroxy-2-phenylethyl)-3-methylimidazolium triflate ([PhHEMIM][OTF]), and a catalytic amount of lithium chloride (1 mol-%). Copyright
- Volkov, Alexey,Buitrago, Elina,Adolfsson, Hans
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supporting information
p. 2066 - 2070
(2013/05/09)
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- Zinc-catalyzed chemoselective reduction of tertiary and secondary amides to amines
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General and convenient procedures for the catalytic hydrosilylation of secondary and tertiary amides under mild conditions have been developed. In the presence of inexpensive zinc catalysts, tertiary amides are easily reduced by applying monosilanes. Key to success for the reduction of the secondary amides is the use of zinc triflate and disilanes with dual Si-H moieties. The presented hydrosilylations proceed with excellent chemoselectivity in the presence of sensitive ester, nitro, azo, nitrile, olefins, and other functional groups, thus making the method attractive for organic synthesis.
- Das, Shoubhik,Addis, Daniele,Junge, Kathrin,Beller, Matthias
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experimental part
p. 12186 - 12192
(2011/11/07)
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- Zinc-catalyzed reduction of amides: Unprecedented selectivity and functional group tolerance
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(Chemical Equation Presented) A novel zinc-catalyzed reduction of tertiary amides was developed. This system shows remarkable chemoselectivity and substrate scope tolerating ester, ether, nitro, cyano, azo, and keto substituents. Copyright
- Das, Shoubhik,Addis, Daniele,Zhou, Shaolin,Junge, Kathrin,Beller, Matthias
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supporting information; experimental part
p. 1770 - 1771
(2010/04/25)
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- LINCOMYCIN DERIVATIVES AND ANTIBACTERIAL AGENTS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
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An objective of the present invention is to provide compounds of formula (1) or their pharmacologically acceptable salts or solvates wherein A represents aryl; R1 represents N-optionally substituted C1-6 alkyl-N-optionally substituted C1-6 alkylamino-C1-6 alkyl; R2 represents a hydrogen atom or optionally substituted C1-6 alkyl; R3 represents optionally substituted C1-6alkyl or C3-6 cycloalkyl-C1-4 alkyl; m is 1 to 3; n is 0; and p is 0 to 2. The compounds are novel lincomycin derivatives that have a potent activity against resistant Streptococcus pneumoniae, which have recently posed problems, in the treatment of infectious diseases. Further, the compounds are usable as antimicrobial agents and are useful for preventing or treating bacterial infectious diseases.
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Page/Page column 39
(2010/03/02)
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- (HETERO)ARYL COMPOUNDS WITH MCH ANTAGONISTIC ACTIVITY AND MEDICAMENTS COMPRISING THESE COMPOUNDS
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The present invention relates to (hetero)aryl compounds of general formula (I) wherein the groups and radicals A, B, Q, W, X, Y, Z, R1, R2, R4a, R4b, R5a, R5b, have the meanings given in cl
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Page/Page column 75
(2010/11/27)
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- Dual serotonin transporter inhibitor/histamine H3 antagonists: Development of rigidified H3 pharmacophores
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A series of tetrahydroisoquinolines acting as dual serotonin transporter inhibitor/histamine H3 antagonists is described. The introduction of polar aromatic spacers as part of the histamine H3 pharmacophore was explored. A convergent synthesis of the final products allowing late stage introduction of the aromatic side chain was developed. In vitro and in vivo data are discussed.
- Keith, John M.,Barbier, Ann J.,Wilson, Sandy J.,Miller, Kirstin,Boggs, Jamin D.,Fraser, Ian C.,Mazur, Curt,Lovenberg, Timothy W.,Carruthers, Nicholas I.
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p. 5325 - 5329
(2008/03/18)
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- NEW DERIVATIVES OF 5-ARYL-1H-PYRROLO [2, 3B] PYRIDINE-3-CARBOXAMIDE OR 5-ARYL-1H-PYRROLO [2, 3B] PYRIDINE-3-CARBOXYLIC ACID
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The present invention relates to new compounds of formula I as a free base or a pharmaceutically acceptable salt, solvate or solvate of salt thereof, a process for their preparation and new intermediates used therein, pharmaceutical formulations containin
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Page/Page column 31-32
(2008/06/13)
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- Phenylalkynes
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Substituted phenylalkynes of formula (I), compositions containing them, and methods of making and using them to treat histamine-mediated conditions.
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- Phenylalkynes
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Substituted phenylalkynes of formula (I), compositions containing them, and methods of making and using them to treat histamine-mediated conditions.
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- Formic Acid Reduction. XXVIII. Kinetic Studies on the Formic Acid Reduction of 1,1'-Benzylidenedipiperidine
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The formic acid reduction of 1,1'-benzylidenedipiperidine (1) was kinetically investigated by the carbon dioxide trapping method.Rate data gave the rate equation, v=kobs.The initial mono- and diprotonation of 1 occur in equilibrium, and monoprotonated form is proposed to be an intermediate for the reduction to 1-benzylpiperidine.The isotope effect value (2.69) and the negative ρ substituent effect (similar to that of the formic acid reduction of N-benzylideneaniline) suggest that the reduction of 1 involves the same intermediate step of decarboxylation of the formic acid ester of the α-amino alcohol.
- Fukawa, Hidemichi,Suzuki, Kunio,Sekiya, Minoru
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p. 2868 - 2873
(2007/10/02)
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