- A simple anion chemosensor based on a naphthalene-thiouronium dyad
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A fluorescent-active molecular dyad comprising a naphthalene moiety covalently attached, via a methylene spacer, to a thiouronium receptor is described where selective anion-induced fluorescence changes make it of potential use as an anion chemosensor material.
- Kubo, Yuji,Tsukahara, Masahiko,Ishihara, Shinji,Tokita, Sumio
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Read Online
- Cysteine-Activated Small-Molecule H2Se Donors Inspired by Synthetic H2S Donors
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The importance of selenium (Se) in biology and health has become increasingly clear. Hydrogen selenide (H2Se), the biologically available and active form of Se, is suggested to be an emerging nitric oxide (NO)-like signaling molecule. Nevertheless, the research on H2Se chemical biology has technique difficulties due to the lack of well-characterized and controllable H2Se donors under physiological conditions, as well as a robust assay for direct H2Se quantification. Motivated by these needs, here, we demonstrate that selenocyclopropenones and selenoamides are tunable donor motifs that release H2Se upon reaction with cysteine (Cys) at pH 7.4 and that structural modifications enable the rate of Cys-mediated H2Se release to be tuned. We monitored the reaction pathways for the H2Se release and confirmed H2Se generation qualitatively using different methods. We further developed a quantitative assay for direct H2Se trapping and quantitation in an aqueous solution, which should also be operative for investigating future H2Se donor motifs. In addition, we demonstrate that arylselenoamide has the capability of Cys-mediated H2Se release in cellular environments. Importantly, mechanistic investigations and density functional theory (DFT) calculations illustrate the plausible pathways of Cys-activated H2Se release from arylselenoamides in detail, which may help understand the mechanistic issues of the H2S release from pharmacologically important arylthioamides. We anticipate that the well-defined chemistries of Cys-activated H2Se donor motifs will be useful for studying Se biology and for development of new H2Se donors and bioconjugate techniques.
- Cai, Xuekang,Cheng, Longhuai,Dong, Yalun,Huang, Haojie,Jiang, Chenyang,Kang, Xueying,Sang, Yueqian,Sun, Lu,Wen, Xin,Xi, Zhen,Yi, Long
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p. 3957 - 3967
(2022/03/08)
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- Zirconium-hydride-catalyzed site-selective hydroboration of amides for the synthesis of amines: Mechanism, scope, and application
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Developing mild and efficient catalytic methods for the selective synthesis of amines is a longstanding research objective. In this respect, catalytic deoxygenative amide reduction has proven to be promising but challenging, as this approach necessitates selective C–O bond cleavage. Herein, we report the selective hydroboration of primary, secondary, and tertiary amides at room temperature catalyzed by an earth-abundant-metal catalyst, Zr-H, for accessing diverse amines. Various readily reducible functional groups, such as esters, alkynes, and alkenes, were well tolerated. Furthermore, the methodology was extended to the synthesis of bio- and drug-derived amines. Detailed mechanistic studies revealed a reaction pathway entailing aldehyde and amido complex formation via an unusual C–N bond cleavage-reformation process, followed by C–O bond cleavage.
- Han, Bo,Jiao, Haijun,Wu, Lipeng,Zhang, Jiong
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p. 2059 - 2067
(2021/09/02)
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- Deoxygenative hydroboration of primary, secondary, and tertiary amides: Catalyst-free synthesis of various substituted amines
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Transformation of relatively less reactive functional groups under catalyst-free conditions is an interesting aspect and requires a typical protocol. Herein, we report the synthesis of various primary, secondary, and tertiary amines through hydroboration of amides using pinacolborane under catalyst-free and solvent-free conditions. The deoxygenative hydroboration of primary and secondary amides proceeded with excellent conversions. The comparatively less reactive tertiary amides were also converted to the corresponding N,N-diamines in moderate yields under catalyst-free conditions, although alcohols were obtained as a minor product.
- An, Duk Keun,Jaladi, Ashok Kumar,Kim, Hyun Tae,Yi, Jaeeun
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- Benzimidazole fragment containing Mn-complex catalyzed hydrosilylation of ketones and nitriles
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The synthesis of a new bidentate (NN)–Mn(I) complex is reported and its catalytic activity towards the reduction of ketones and nitriles is studied. On comparing the reactivity of various other Mn(I) complexes supported by benzimidazole ligand, it was observed that the Mn(I) complexes bearing 6-methylpyridine and benzimidazole fragments exhibited the highest catalytic activity towards monohydrosilylation of ketones and dihydrosilylation of nitriles. Using this protocol, a wide range of ketones were selectively reduced to the corresponding silyl ethers. In case of unsaturated ketones, the chemoselective reduction of carbonyl group over olefinic bonds was observed. Additionally, selective dihydrosilylation of several nitriles were also achieved using this complex. Mechanistic investigations with radical scavengers suggested the involvement of radical species during the catalytic reaction. Stoichiometric reaction of the Mn(I) complex with phenylsilane revealed the formation of a new Mn(I) complex.
- Ganguli, Kasturi,Mandal, Adarsha,Sarkar, Bidisha,Kundu, Sabuj
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supporting information
(2020/08/13)
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- Method for preparing primary amine by catalyzing reductive amination of aldehyde ketone compounds
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The invention discloses a method for preparing primary amine by catalyzing reductive amination of aldehyde ketone compounds. The method comprises the following steps: 1) mixing nickel nitrate hexahydrate, citric acid and an organic solvent, carrying out heating and stirring until a colloidal material is obtained, drying the colloidal material, roasting the colloidal material in a protective atmosphere, pickling, washing and drying a roasted product, and performing a partial oxidation reaction on a dried product in an oxygen-nitrogen mixed atmosphere to obtain a catalyst for a reductive amination reaction; and 2) mixing aldehyde or ketone compounds, a methanol solution of ammonia and the reductive amination reaction catalyst, introducing hydrogen, and carrying out a reductive amination reaction. The method has the advantages of high primary amine yield, high selectivity, wide aldehyde ketone substrate range, short reaction time, mild reaction conditions, low cost, greenness, economicalperformance and the like; the used reductive amination reaction catalyst can be recycled more than 10 times, and the catalytic activity of the catalyst is not obviously changed in gram-level reactions; and the method is suitable for large-scale application.
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Paragraph 0049-0050
(2020/05/30)
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- Facile synthesis of controllable graphene-co-shelled reusable Ni/NiO nanoparticles and their application in the synthesis of amines under mild conditions
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The primary objective of many researchers in chemical synthesis is the development of recyclable and easily accessible catalysts. These catalysts should preferably be made from Earth-abundant metals and have the ability to be utilised in the synthesis of pharmaceutically important compounds. Amines are classified as privileged compounds, and are used extensively in the fine and bulk chemical industries, as well as in pharmaceutical and materials research. In many laboratories and in industry, transition metal catalysed reductive amination of carbonyl compounds is performed using predominantly ammonia and H2. However, these reactions usually require precious metal-based catalysts or RANEY nickel, and require harsh reaction conditions and yield low selectivity for the desired products. Herein, we describe a simple and environmentally friendly method for the preparation of thin graphene spheres that encapsulate uniform Ni/NiO nanoalloy catalysts (Ni/NiO?C) using nickel citrate as the precursor. The resulting catalysts are stable and reusable and were successfully used for the synthesis of primary, secondary, tertiary, and N-methylamines (more than 62 examples). The reaction couples easily accessible carbonyl compounds (aldehydes and ketones) with ammonia, amines, and H2 under very mild industrially viable and scalable conditions (80 °C and 1 MPa H2 pressure, 4 h), offering cost-effective access to numerous functionalized, structurally diverse linear and branched benzylic, heterocyclic, and aliphatic amines including drugs and steroid derivatives. We have also demonstrated the scale-up of the heterogeneous amination protocol to gram-scale synthesis. Furthermore, the catalyst can be immobilized on a magnetic stirring bar and be conveniently recycled up to five times without any significant loss of catalytic activity and selectivity for the product.
- Cui, Zhibing,Liu, Jianguo,Liu, Qiying,Ma, Longlong,Singh, Thishana,Wang, Chenguang,Wang, Nan,Zhu, Yuting
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supporting information
p. 7387 - 7397
(2020/11/19)
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- Synthesis of Secondary Aldimines from the Hydrogenative Cross-Coupling of Nitriles and Amines over Al2O3-Supported Ni Catalysts
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A heterogeneous Ni catalyst was discovered to be active in the synthesis of secondary cross-imines via hydrogenative coupling of nitriles and amines. The mesoporous Al2O3-supported Ni nanoparticles (abbreviated as Ni/m-Al2O3-600, where 600 represents the reduction temperature) were active in hydrogenative coupling of nitriles and amines reaction at 80 °C and 1 bar H2, affording corresponding cross-imines with yields in the range 64.1-98.1%. Density functional theory calculations reveal the hydrogenation of benzonitrile (PhCN) to benzylamine (PhCH2NH2) has higher activation energy than that for hydrogenative cross-coupling of PhCN and RNH2 on the Ni/m-Al2O3-600 catalyst, suggesting the latter reaction is more favorable. The theoretical calculations are in good agreement with our experimental results.
- Zhou, Peng,Jiang, Liang,Wang, Shuguo,Hu, Xun,Wang, Hongming,Yuan, Ziliang,Zhang, Zehui
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p. 8413 - 8423
(2019/09/07)
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- Preparation of nitrogen-doped carbon supported cobalt catalysts and its application in the reductive amination
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The use of non-noble metal catalysts with high activity is of great importance for organic transformations. Herein, nitrogen-doped carbon supported cobalt catalysts with high surface area up to 981.2 m2/g were prepared via the simple pyrolysis of cobalt coordinated organic polymers with silica as the hard template. The pyrolysis temperature showed a great effect on the structure and properties of the as-prepared catalysts. The Co@NC-800 catalyst with the pyrolysis temperature of 800 °C demonstrated a high activity for the selective reductive amination of carbonyl compounds to primary amines with ammonia and hydrogen. Structurally-diverse primary amines with yields in the range from 81.8% to 100% were attained under the optimal conditions. The Co@NC-800 catalyst could be reused without the loss of its activity. The Co@NC-800 catalyst demonstrated comparable activity as the reported heterogeneous noble metal catalysts.
- Yuan, Ziliang,Liu, Bing,Zhou, Peng,Zhang, Zehui,Chi, Quan
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p. 347 - 356
(2019/01/24)
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- Cobalt pincer complexes for catalytic reduction of nitriles to primary amines
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Various cobalt pincer type complexes 1-6 were applied for the catalytic hydrogenation of nitriles to amines. Among these, catalyst 4 is the most efficient, allowing the reduction of aromatic as well as aliphatic nitriles in moderate to excellent yields.
- Schneek?nig, Jacob,Tannert, Bianca,Hornke, Helen,Beller, Matthias,Junge, Kathrin
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p. 1779 - 1783
(2019/04/27)
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- Nitrogen-Doped Carbon-Supported Nickel Nanoparticles: A Robust Catalyst to Bridge the Hydrogenation of Nitriles and the Reductive Amination of Carbonyl Compounds for the Synthesis of Primary Amines
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An efficient method was developed for the synthesis of primary amines either from the hydrogenation of nitriles or reductive amination of carbonyl compounds. The reactions were catalyzed by nitrogen-doped mesoporous carbon (MC)-supported nickel nanoparticles (abbreviated as MC/Ni). The MC/Ni catalyst demonstrated high catalytic activity for the hydrogenation of nitriles into primary amines in high yields (81.9–99 %) under mild reaction conditions (80 °C and 2.5 bar H2). The MC/Ni catalyst also promoted the reductive amination of carbonyl compounds for the synthesis of primary amines at 80 °C and 1 bar H2. The hydrogenation of nitriles and the reductive amination proceeded through the same intermediates for the generation of the primary amines. To the best of our knowledge, no other heterogeneous non-noble metal catalysts have been reported for the synthesis of primary amines under mild conditions, both from the hydrogenation of nitriles and reductive amination.
- Zhang, Yangmin,Yang, Hanmin,Chi, Quan,Zhang, Zehui
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p. 1246 - 1255
(2019/03/07)
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- N-Alkylation of Aqueous Ammonia with Alcohols Leading to Primary Amines Catalyzed by Water-Soluble N-Heterocyclic Carbene Complexes of Iridium
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A new catalytic system for the N-monoalkylation of aqueous ammonia with a variety of alcohols was developed. Water-soluble dicationic complexes of iridium bearing N-heterocyclic carbene and diammine ligands exhibited high catalytic activity for this type of reaction on the basis of hydrogen-transfer processes without generating harmful or wasteful byproducts. Various primary amines were efficiently synthesized by using safe, inexpensive, and easily handled aqueous ammonia as a nitrogen source. For example, the reaction of 1-(4-methylphenyl)ethanol with aqueous ammonia in the presence of a water-soluble N-heterocyclic carbene complex of iridium at 150 °C for 40 h gave 1-(4-methylphenyl)ethylamine in 83 % yield.
- Fujita, Ken-Ichi,Furukawa, Shohichi,Morishima, Namino,Shimizu, Mineyuki,Yamaguchi, Ryohei
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p. 1993 - 1997
(2018/03/13)
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- Systematic structure-activity relationship (SAR) exploration of diarylmethane backbone and discovery of a highly potent novel uric acid transporter 1 (URAT1) inhibitor
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In order to systematically explore and better understand the structure-activity relationship (SAR) of a diarylmethane backbone in the design of potent uric acid transporter 1 (URAT1) inhibitors, 33 compounds (1a-1x and 1ha-1hi) were designed and synthesized, and their in vitro URAT1 inhibitory activities (IC50) were determined. The three-round systematic SAR exploration led to the discovery of a highly potent novel URAT1 inhibitor, 1h, which was 200-and 8-fold more potent than parent lesinurad and benzbromarone, respectively (IC50 = 0.035 μM against human URAT1 for 1h vs. 7.18 μM and 0.28 μM for lesinurad and benzbromarone, respectively). Compound 1h is the most potent URAT1 inhibitor discovered in our laboratories so far and also comparable to the most potent ones currently under development in clinical trials. The present study demonstrates that the diarylmethane backbone represents a very promising molecular scaffold for the design of potent URAT1 inhibitors.
- Cai, Wenqing,Wu, Jingwei,Liu, Wei,Xie, Yafei,Liu, Yuqiang,Zhang, Shuo,Xu, Weiren,Tang, Lida,Wang, Jianwu,Zhao, Guilong
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- Highly Stable COF-Supported Co/Co(OH)2 Nanoparticles Heterogeneous Catalyst for Reduction of Nitrile/Nitro Compounds under Mild Conditions
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Ordered nanoporosity in covalent organic framework (COF) offers excellent opportunity for property development. Loading nanoparticles (nPs) onto them is one approach to introducing tailor-made properties into a COF. Here, a COF–Co/Co(OH)2 composite containing about 16 wt% of 2 nPs is prepared on a N-rich COF support that catalyzes the release of theoretical equivalence of H2 from readily available, safe, and cheap NaBH4. Furthermore, the released H2 is utilized for the hydrogenation of nitrile and nitro compounds to amines under ambient conditions in a facile one-pot reaction. The COF “by choice” is built from “methoxy” functionalized dialdehydes which is crucial in enabling the complete retention of the COF structure under the conditions of the catalysis, where the regular Schiff bonds would have hydrolyzed. The N-rich binding pockets in the COF ensure strong nP–COF interactions, which provides stability and enables catalyst recycling. Modeling studies reveal the crucial role played by the COF in exposing the active facets and thereby in controlling the activation of the reducing agent. Additionally, via density functional theory, we provide a rational explanation for how these COFs can stabilize nanoparticles which grow beyond the limiting pore size of the COF and yet result in a truly stable heterogeneous catalyst – a ubiquitous observation. The study underscores the versatility of COF as a heterogeneous support for developing cheap and highly active nonnoble metal catalysts.
- Mullangi, Dinesh,Chakraborty, Debanjan,Pradeep, Anu,Koshti, Vijay,Vinod, Chathakudath P.,Panja, Soumendranath,Nair, Sunil,Vaidhyanathan, Ramanathan
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- MOF-derived cobalt nanoparticles catalyze a general synthesis of amines
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The development of base metal catalysts for the synthesis of pharmaceutically relevant compounds remains an important goal of chemical research. Here, we report that cobalt nanoparticles encapsulated by a graphitic shell are broadly effective reductive amination catalysts. Their convenient and practical preparation entailed template assembly of cobaltdiamine- dicarboxylic acid metal organic frameworks on carbon and subsequent pyrolysis under inert atmosphere.The resulting stable and reusable catalysts were active for synthesis of primary, secondary, tertiary, and N-methylamines (more than 140 examples).The reaction couples easily accessible carbonyl compounds (aldehydes and ketones) with ammonia, amines, or nitro compounds, and molecular hydrogen under industrially viable and scalable conditions, offering cost-effective access to numerous amines, amino acid derivatives, and more complex drug targets.
- Jagadeesh, Rajenahally V.,Murugesan, Kathiravan,Alshammari, Ahmad S.,Neumann, Helfried,Pohl, Marga-Martina,Radnik, J?rg,Beller, Matthias
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p. 326 - 332
(2017/09/28)
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- Selective hydrogenation of nitriles to primary amines catalyzed by a novel iron complex
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Hydrogenation of nitriles to primary amines constitutes an atom-efficient and environmentally benign synthetic reaction. Herein we present a novel complex based on earth-abundant iron, and its application in the catalytic homogeneous hydrogenation of (hetero)aromatic, benzylic, and aliphatic nitriles to selectively form primary amines.
- Chakraborty, Subrata,Leitus, Gregory,Milstein, David
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supporting information
p. 1812 - 1815
(2016/02/05)
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- Ruthenium(II) 9,10-phenanthrenequinone thiosemicarbazone complexes: Synthesis, characterization, and catalytic activity towards the reduction as well as condensation of nitriles
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The ligands 9,10-phenanthrenequinone-N4-substituted thiosemicarbazones (HL1-3) and their ruthenium(II) complexes were synthesized and characterized by elemental and spectroscopic methods. The ligands are tridentate, monobasic chelating ligands with O, N, and S as the donor sites and are in the thiol form in all the complexes. Catalytic studies showed that all the complexes displayed good catalytic activity towards the reduction of nitriles and also the condensation of nitriles with 2-aminoalcohol under solvent-free conditions.
- Anitha, Panneerselvam,Viswanathamurthi, Periasamy,Kesavan, Devarayan,Butcher, Ray Jay
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p. 321 - 334
(2015/10/20)
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- Synthesis of the calcilytic ligand NPS 2143
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(R)-3 (NPS 2143) is a negative allosteric modulator of the human calcium-sensing receptor (CaSR) and as such represents an important pharmacological tool compound for studying the CaSR. Herein, we disclose for the first time a complete experimental description, detailed characterisation and assessment of enantiomeric purity for (R)-3. An efficient, reproducible and scalable synthesis of (R)-3 that requires a minimum of chromatographic purification steps is presented. (R)-3 was obtained in excellent optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature.
- Johansson, Henrik,Cailly, Thomas,Thomsen, Alex Rojas Bie,Braeuner-Osborne, Hans,Pedersen, Daniel Sejer
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supporting information
p. 1383 - 1387
(2013/08/23)
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- 1,2,3-Trimethoxypropane, a glycerol-based solvent with low toxicity: New utilization for the reduction of nitrile, nitro, ester, and acid functional groups with TMDS and a metal catalyst
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1,2,3-Trimethoxypropane (1,2,3-TMP) was prepared from glycerol in one step in good yield and selectivity by phase transfer catalysis. According to OECD guidelines, a toxicity study was realized for this compound. It revealed that 1,2,3-TMP has a low acute toxicity, no skin sensitization, no mutagenicity and no ecotoxicity in an aquatic environment. This compound was also used as a solvent for the reduction of organic functions using either aluminium hydride or 1,1,3,3-tetramethyldisiloxane (TMDS) as a benign hydride source. In particular, a new process for the reduction of nitriles to amines in 2-MeTHF and in 1,2,3-TMP was developed, using TMDS in combination with copper triflate (Cu(OTf)2).
- Sutter, Marc,Pehlivan, Leyla,Lafon, Romain,Dayoub, Wissam,Raoul, Yann,Metay, Estelle,Lemaire, Marc
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supporting information
p. 3020 - 3026
(2013/11/06)
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- One-pot primary aminomethylation of aryl and heteroaryl halides with sodium phthalimidomethyltrifluoroborate
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A one-pot primary aminomethylation of aryl halides, triflates, mesylates, and tosylates via Suzuki-Miyaura cross-coupling reactions with sodium phthalimidomethyltrifluoroborate followed by deamidation with ethylenediamine is reported.
- Murai, Norio,Miyano, Masayuki,Yonaga, Masahiro,Tanaka, Keigo
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p. 2818 - 2821
(2012/07/17)
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- Synthesis of unusual oxime ethers by reaction of tetranitromethane with B-alkylcatecholboranes
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The reaction of tetranitromethane with B-alkylcatecholboranes leads to the formation of unusual dinitrooxime ethers. A tentative mechanism is provided, which suggests the involvement of extremely fast addition of alkyl radicals to tetranitromethane. The substitution of one of the nitro groups in the oxime ethers by nucleophiles (such as secondary amines, halogens and styrene) and by radicals generated from B-alkylcatecholboranes is reported.
- Luethy, Monique,Schenk, Kurt,Renaud, Philippe
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supporting information; experimental part
p. 10171 - 10177
(2010/12/19)
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- SUBSTITUTED BENZOTRIAZINES AND QUINOXALINES AS INHIBITORS OF P7OS6 KINASE
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The invention provides compounds of the formula (1): or salts or tautomers thereof; wherein X1 is N or N+(O ); X2 is N or CH; Q is a C1-3 alkylene group; R1 is selected from hydrogen, C1-4 hydrocarbyl and hydroxy-C2-4 hydrocarbyl; R2, R3 and R4 are the same or different and each is selected from hydrogen, fluorine, chlorine and methyl; Ar1 is an optionally substituted monocyclic 5 or 6-membered aryl or heteroaryl ring containing 0, 1 or 2 heteroatom ring members selected from O, N and S, or a naphthyl ring and Ar2 is an optionally substituted monocyclic 5 or 6-membered heteroaryl ring containing 1, 2 or 3 heteroatom ring members selected from O, N and S. The compounds of formula (1) are inhibitors of p70S6 kinase and are useful in the treatment of proliferative diseases.
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Page/Page column 65; 66
(2010/12/26)
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- Borrowing hydrogen methodology for the conversion of alcohols into N-protected primary amines and in situ deprotection
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Alcohols have been converted into a range of protected amines including sulfonamides and N-alkylbenzylamine derivatives. Representative examples of deprotection to afford primary amines are also provided.
- Lamb, Gareth W.,Watson, Andrew J.A.,Jolley, Katherine E.,Maxwell, Aoife C.,Williams, Jonathan M.J.
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supporting information; experimental part
p. 3374 - 3377
(2009/09/05)
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- Fine-tuning catalytic activity and selectivity-[Rh(amino acid thioamide)] complexes for efficient ketone reduction
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Amino acid-derived thioamides are prepared and evaluated as ligands in the rhodium-catalyzed asymmetric transfer hydrogenation of ketones in 2-propanol. It is found that increasing the steric bulk at the C-terminus of the ligand had a positive impact on both activity and selectivity in the reduction reaction. In order to find the optimum catalyst, a study is performed on a series of thioamide ligands having substituents of varying size.
- Ahlford, Katrin,Livendahl, Madeleine,Adolfsson, Hans
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supporting information; experimental part
p. 6321 - 6324
(2010/02/28)
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- HYDRAZIDE, AMIDE, PHTHALIMIDE AND PHTHALHYDRAZIDE ANALOGS AS INHIBITORS OF RETROVIRAL INTEGRASE
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The present invention provides catechol-containing hydrazides, amides, phthalimide and phthalhydrazide analogs. These compounds are inhibitors of retroviral integrase, an essential enzyme for the proliferation of retroviruses such as HIV-1. Also provided are pharmaceutical compositions comprising at least one of the catechol-containing hydrazides, amides, phthalimide or phthalhydrazide analogs and a method of using the hydrazide, amide, phthalimide and phthalhydrazide analogs to inhibit retroviral proliferation and as therapeutics for the treatment of AIDS.
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Page/Page column 101
(2009/04/25)
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- Rapid and convenient microwave-assisted synthesis of primary amines via reductive N-alkylation of methyl carbamate with aldehydes
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Microwave-assisted reductive alkylation of methyl carbamate with a range of aldehydes provides, after basic work-up, an experimentally simple, one-pot method for rapid functional group interconversion of structurally diverse aldehydes into primary amines. The method has several advantages over more traditional methods of carrying out this transformation and is particularly amenable to high-throughput synthesis.
- Lehmann, Fredrik,Scobie, Martin
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p. 1679 - 1681
(2008/12/22)
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- Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus
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The first step in HIV infection is the binding of the envelope glycoprotein gp120 to the host cell receptor CD4. An interfacial "Phe43 cavity" in gp120, adjacent to residue Phe43 of gp120-bound CD4, has been suggested as a potential target for therapeutic intervention. We designed a CD4 mutant (D1D2F43C) for site-specific coupling of compounds for screening against the cavity. Altogether, 81 cysteine-reactive compounds were designed, synthesized, and tested. Eight derivatives exceeded the affinity of native D1D2 for gp120. Structure-activity relationships (SAR) for derivatized CD4 binding to gp120 revealed significant plasticity of the Phe43 cavity and a narrow entrance. The primary contacts for compound recognition inside the cavity were found to be van der Waals interactions, whereas hydrophilic interactions were detected in the entrance. This first SAR on ligand binding to an interior cavity of gp120 may provide a starting point for structure-based assembly of small molecules targeting gp120-CD4 interaction.
- Xie, Hui,Ng, Danny,Savinov, Sergey N.,Dey, Barna,Kwong, Peter D.,Wyatt, Richard,Smith III, Amos B.,Hendrickson, Wayne A.
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p. 4898 - 4908
(2008/03/11)
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- Novel IDO inhibitors and methods of use thereof
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Novel indoleamine 2,3-dioxygenase (IDO) inhibitors, compositions comprising the same, and methods of use thereof are disclosed.
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Page/Page column Sheet 3/7; 10
(2010/11/27)
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- Purinenucleoside derivative modified in 8-position and medical use thereof
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The present invention provides an 8-modified purinenucleoside derivative which is useful for diseases associated with an abnormality of plasma uric acid level. An 8-modified purinenucleoside derivative represented by the following formula (I), a prodrug thereof or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, is useful for the prevention or treatment of gout, hyperuricemia, urinary lithiasis, hyperuricemic nephropathy or the like. In the formula, n is 1 or 2; RA is a hydrogen atom or a hydroxyl group; R1 is a hydrogen atom, a hydroxyl group, a thiol group, an amino group or a chlorine atom; ring J represents an optionally substituted 2-naphthyl group, or a group represented by the following general formula (II) wherein Y represents a single bond or a connecting group; ring Z represents an optionally substituted aryl group or heteroaryl group or the like; and R2 to R4, P1 and Q represents a halogen atom, a cyano group or the like.
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Page/Page column 25
(2010/11/28)
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- Structure-activity study of brassinin derivatives as indoleamine 2,3-dioxygenase inhibitors
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A screen of indole-based structures revealed the natural product brassinin to be a moderate inhibitor of indoleamine 2,3-dioxygenase (IDO), a new cancer immunosuppression target. A structure-activity study was undertaken to determine which elements of the brassinin structure could be modified to enhance potency. Three important discoveries have been made, which will impact future IDO inhibitor development: (i) The dithiocarbamate portion of the brassinin lead is a crucial moiety, which may be binding to the heme iron of IDO; (ii) an indole ring is not necessary for IDO inhibition; and (iii) substitution of the S-methyl group of brassinin with large aromatic groups provides inhibitors that are three times more potent in vitro than the most commonly used IDO inhibitor, 1-methyl-tryptophan.
- Gaspari, Paul,Banerjee, Tinku,Malachowski, William P.,Muller, Alexander J.,Prendergast, George C.,DuHadaway, James,Bennett, Shauna,Donovan, Ashley M.
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p. 684 - 692
(2007/10/03)
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- Reductive amination of aldehydes using aminoboranes as iminium ion generators
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2-Dialkylamino-4H-1,3,2-benzodioxaborins, salicyl alcohol derived aminoboranes, serve as efficient and mild iminium ion generators in the reductive animation of aldehydes with NaBH4. Using a diisopropylamino derivative, a variety of amines including secondary and primary amines, and ammonia can participate to the reductive amination in aprotic organic solvents without the use of acidic promoters. Georg Thieme Verlag Stuttgart.
- Suginome, Michinori,Tanaka, Yusuke,Hasui, Tomoaki
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p. 1047 - 1050
(2007/10/03)
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- The discovery and preparation of disubstituted novel amino-aryl-piperidine- based renin inhibitors
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Recently, trans-disubstituted oxo-aryl-piperidines have been identified as small molecule nonpeptide renin inhibitors for the modulation of hypertension. Herein, we report on the discovery and preparation of a new class of novel cis-disubstituted amino-aryl-piperidines as a mixture of enantiomers that are potent in vitro renin inhibitors and also, possess in vivo antihypertensive activity in a double transgenic mouse model.
- Cody, Wayne L.,Holsworth, Daniel D.,Powell, Noel A.,Jalaie, Mehran,Zhang, Erli,Wang, Wei,Samas, Brian,Bryant, John,Ostroski, Robert,Ryan, Michael J.,Edmunds, Jeremy J.
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- AMIDE COMPOUND AND METHOD OF CONTROLLING PLANT DISEASE WITH THE SAME
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A amid compound of the formula (1): wherein, in the formula, R51 represents a halogen atom, a C1-C6 alkyl group and the like; R52 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group and the like; R53 represents a halogen atom and the like; R56 represents a halogen atom and the like; R57 represents a hydrogen atom and the like; R58 and R59 independently represent a hydrogen atom, a C1-C3 alkyl group and the like; R60 represents a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C4 alkenyl group, or a C3-C6 alkynyl group; R61 represents a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C3-C4 alkenyl group or a C3-C6 alkynyl group or a C2-C4 cyanoalkyl group; R62, R63 and R64 represent a hydrogen atom, a halogen atom and the like; X represents a oxygen atom or a sulfur atom; has an excellent activity against plant diseases.
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Page/Page column 101
(2010/02/14)
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- AMIDE COMPOUND AND USE OF THE SAME
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PROBLEM TO BE SOLVED: To provide a compound having an excellent controlling effect against plant pests. SOLUTION: This amide compound expressed by formula (1) [wherein, R1 is H, a halogen atom, a 1-4C alkyl or the like; R2 is a 1-4C alkyl, a 1-4C haloalkyl or the like; R3 is H or a 1-3C alkyl; R4 is a halogen, a 1-4C alkylthio, a 2-5C alkylcarbonyloxy or the like; R5 is a 3-4C alkynyl; and X is O or S] has the excellent controlling effect against the plant pests. COPYRIGHT: (C)2006,JPOandNCIPI
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Page/Page column 55-56
(2010/02/14)
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- Fungicidal Composition
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A fungicidal composition comprising: an amide compound represented by formula (1) and dimethomorph as active ingredients, and a method for controlling plant diseases applying effective amount of an amide compound represented by formula (1) and dimethomorph to plant(s) or soil where plant(s) are growing.
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Page/Page column 19
(2010/02/15)
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- BETA-STRAND MIMETICS AND METHOD RELATING THERETO
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Conformationally constrained compounds which mimic the secondary structure of ?-strand regions of biologically active peptides and proteins are disclosed. Such ?-strand mimetic structures have utility over a wide range of fields, including use as diagnostic and therapeutic agents. Libraries containing the ?-strand mimetic structures of this invention are also disclosed as well as methods for screening the same to identify biologically active members.
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- Detoxification of the cruciferous phytoalexin brassinin in Sclerotinia sclerotiorum requires an inducible glucosyltransferase
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The phytoalexins, brassinin, 1-methoxybrassinin and cyclobrassinin, were metabolized by the stem rot fungus Sclerotinia sclerotiorum into their corresponding glucosyl derivatives displaying no detectable antifungal activity. Importantly, co-incubation of S. sclerotiorum with camalexins, various phytoalexin analogs, and brassinin indicated that a synthetic camalexin derivative could slow down substantially the rate of brassinin detoxification. Furthermore, inducible brassinin glucosyltransferase (BGT) activity was detected in crude cell-free extracts of S. sclerotiorum. BGT activity was induced by the phytoalexin camalexin, and the brassinin analogs methyl tryptamine dithiocarbamate and methyl 1-methyltryptamine dithiocarbamate. The overall results suggest that the fungus S. sclerotiorum in its continuous adaptation and co-evolution with brassinin producing plants, has acquired efficient glucosyltransferase(s) that can disarm some of the most active plant chemical defenses.
- Pedras, M. Soledade C.,Ahiahonu, Pearson W.K.,Hossain, Mohammad
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p. 2685 - 2694
(2007/10/03)
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- Beta-strand mimetics and method relating thereto
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Conformationally constrained compounds which mimic the secondary structure of β-strand regions of biologically active peptides and proteins are disclosed. Such β-strand mimetic structures have utility over a wide range of fields, including use as diagnostic and therapeutic agents. Libraries containing the β-strand mimetic structures of this invention are also disclosed as well as methods for screening the same to identify biologically active members.
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- Piperidine derivative rennin inhibitors
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Disclosed are piperidine derivatives, their manufacture and use as inhibitors of renin.
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Page/Page column 17
(2010/02/08)
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- ROMPgel-Supported Triphenylphosphine with Potential Application in Parallel Synthesis
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(Equation Presented) ROMPgel-supported triphenylphosphine was synthesized in three steps (67%) from norbornadiene, 4-bromoiodobenzene, and chlorodiphenylphosphine. The supported reagent has a high loading (2.5 mmol/g) and favorable swelling properties in organic solvents. It has been utilized for the conversion of alcohols to halides, the reduction of ozonides, and the isomerization of α,β-acetylenic esters and in the Staudinger reaction. In general, filtration of the resin from the reaction mixtures and evaporation gave the corresponding products in high yield and purity.
- Arstad, Erik,Barrett, Anthony G. M.,Hopkins, Brian T.,Koebberling, Johannes
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p. 1975 - 1977
(2007/10/03)
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- Reductive coupling of aromatic oxims and azines to 1,2-diamines using Zn-MsOH or Zn-TiCl4
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The reduction of aromatic aldoxims and azines with Zn in the presence of MsOH or TiCl4 afforded N,N′-unsubstituted 1,2-diamines in one-step. The reductive coupling with Zn-MsOH gave meso 1,2-diamines selectively, whereas dl 1,2-diamines were fo
- Kise, Naoki,Ueda, Nasuo
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p. 2365 - 2368
(2007/10/03)
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- Improved synthesis of (R)-glycine-d-15N
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Previously, we have synthesized the title glycine to permit assignment of the prochiral α-protons of glycine residues in the NMR study of the protein FKBP. A key, and low yielding step in this synthesis occurs in the ruthenium tetraoxide mediated degradation of N-t-Boc-p-methoxybenzyl amine to N-t-Boc-glycine. Efforts to improve this key step by exploring different substrates and N-protecting groups were successful to render this synthesis amenable for the large scale production of (R)-glycine-d-15N.
- Walker, Joel R,Curley Jr., Robert W
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p. 6695 - 6701
(2007/10/03)
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- Mass spectrometric investigation of tautomers of N-substituted 4-iminopentan-2-ones in the gas phase
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Mass fragmentation of 4-iminopentan-2-one N-substituted with organosilicon group suggests that in the gas phase upon electron ionization (EI) conditions only 4-imino-2-keto tautomer occurs. The simultaneous occurrence of 4-aminopent-3-en-2-keto tautomeric form was ruled out on the basis of mass fragmentation of some alkylaromatic derivatives of 4-aminopent-3-en-2-one.
- Urbaniak,Franski,Gierczyk
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p. 429 - 441
(2007/10/03)
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- Indium Mediated Reduction of Nitro and Azide Groups in the Presence of HCl in Aqueous Media
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Indium mediated reduction of azide and nitro groups in the presence of HCl (1.5 equiv based on indium) at room temperature in aqueous THF successfully provided the corresponding amine in high to quantitative yields. Under the some reaction conditions, selective reduction of azide and nitro group in the presence of vinyl group could be accomplished.
- Lee, Jung Gyu,Choi, Kyung Il,Koh, Hun Yeong,Kim, Youseung,Kang, Yonghan,Cho, Yong Seo
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- Adenosine analogues as selective inhibitors of glyceraldehyde-3-phosphate dehydrogenase of trypanosomatidae via structure-based drug design
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In our continuation of the structure-based design of anti-trypanosomatid drugs, parasiteselective adenosine analogues were identified as low micromolar inhibitors of glyceraldehyde3-phosphate dehydrogenase (GAPDH). Crystal structures of Trypanosoma brucei, Trypanosoma cruzi, Leishmania mexicana, and human GAPDH's provided details of how the adenosyl moiety of NAD+ interacts with the proteins, and this facilitated the understanding of the relative affinities of a series of adenosine analogues for the various GAPDH's. From exploration of modifications of the naphthalenemethyl and benzamide substituents of a lead compound, N6-(1-naphthalenemethyl)-2′-deoxy-2′- (3-methoxybenzamido)adenosine (6e), N6-(substituted-naphthalenemethyl)-2′-deoxy-2′- (substituted-benzamido)adenosine analogues were investigated. N6(1 -Naphthalenemethyl)-2′-deoxy-2′-(3,5-dimethoxybenzamido)adenosine (6m), N6- [1-(3-hydroxynaphthalene)methyl]-2′-deoxy-2′- (3,5-dimethoxybenzamido)adenosine (7m), N6-[1-(3-methoxynaphthalene)methyl]-2′-deoxy-2′- (3,5-dimethoxybenzamido)adenosine (9m), N6-(2-naphthalenemethyl)-2′-deoxy-2′1- (3-methoxybenzamido)adenosine (11e), and N6-(2-naphthalenemethyl)-2′deoxy-2′- (3,5-dimethoxybenzamido)adenosine (11m) demonstrated a 2- to 3-fold improvement over 6e and a 7100- to 25000-fold improvement over the adenosine template. IC50'S of these compounds were in the range 2-12 μM for T. brucei, T. cruzi, and L. mexicana GAPDH's, and these compounds did not inhibit mammalian GAPDH when tested at their solubility limit. To explore more thoroughly the structure- activity relationships of this class of compounds, a library of 240 N6-(substituted)-2′-deoxy-2′-(amido)adenosine analogues was generated using parallel solution-phase synthesis with N6 and C2′ substituents chosen on the basis of computational docking scores. This resulted in the identification of 40 additional compounds that inhibit parasite GAPDH's in the low micromolar range. We also explored adenosine analogues containing 5′-amido substituents and found that 2′,5′-dideoxy-2′-(3,5-dimethoxybenzamido)-5′- (diphenylacetamido)adenosine (49) displays an IC50 of 60-100 μM against the three parasite GAPDH's.
- Bressi,Verlinde,Aronov,Shaw,Shin,Nguyen,Suresh,Buckner,van Voorhis,Kuntz,Hol,Gelb
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p. 2080 - 2093
(2007/10/03)
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- Luminescence behaviour of cadmium, lead, zinc, copper, nickel and lanthanide complexes of octadentate macrocyclic ligands bearing naphthyl chromophores
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The luminescence behaviour of two macrocyclic ligands incorporating naphthyl fluorophores has been studied in water and acetonitrile.The ligands 1,4,7-tris(methylcarbamoylmethyl)-10-(2-naphthylmethyl-carbamoylmethyl)-1,4,7,10-teraazacyclododecane, 1 and 1,4,7,10 tetrakis(2-naphthylmethylcarbamoylmethyl-1,4,7,10-tetraazacyclododecane, 2, exhibit distinctive luminescence behaviour in the presence of quenching (e.g., PbII, CuII and NiII) and non-quenching ions (e.g., CdII and ZnII).The protonated tetranaphthyl ligand forms a well-defined excimer in which excimer emission is a sensitive probe of solvent polarity.The naphtyl group serves as an antenna for energy transfer to the photophorescent bound europium ion and amide N-H coupling provides a significant deactivation mechanism for the excited Eu 5D0 state.
- Parker, David,Williams, J.A.Gareth
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p. 1305 - 1314
(2007/10/03)
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- Reductions of carboxylic acids and their derivatives using samarium diiodide-acid system
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Carboxylic acid was converted to alcohol in a facile-rapid reduction using samarium diiodide in protic solvent under a basic or acidic medium at room temperature in high yield. A similar reaction of ester and anhydride reduced to the corresponding alcohol as the major products and nitrile afforded amine. Amide was rapidly reduced under a basic medium to afford alcohol, but the reduction with samarium diiodide-acid system of amide gave aldehyde in quantitative yield.
- Kamochi,Kudo
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p. 4301 - 4312
(2007/10/02)
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