- Aerobic oxidation of primary amines to amides catalyzed by an annulated mesoionic carbene (MIC) stabilized Ru complex
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Catalytic aerobic oxidation of primary amines to the amides, using the precatalyst [Ru(COD)(L1)Br2] (1) bearing an annulated π-conjugated imidazo[1,2-a][1,8]naphthyridine-based mesoionic carbene ligand L1, is disclosed. This catalytic protocol is distinguished by its high activity and selectivity, wide substrate scope and modest reaction conditions. A variety of primary amines, RCH2NH2 (R = aliphatic, aromatic and heteroaromatic), are converted to the corresponding amides using ambient air as an oxidant in the presence of a sub-stoichiometric amount of KOtBu in tBuOH. A set of control experiments, Hammett relationships, kinetic studies and DFT calculations are undertaken to divulge mechanistic details of the amine oxidation using 1. The catalytic reaction involves abstraction of two amine protons and two benzylic hydrogen atoms of the metal-bound primary amine by the oxo and hydroxo ligands, respectively. A β-hydride transfer step for the benzylic C-H bond cleavage is not supported by Hammett studies. The nitrile generated by the catalytic oxidation undergoes hydration to afford the amide as the final product. This journal is
- Yadav, Suman,Reshi, Noor U Din,Pal, Saikat,Bera, Jitendra K.
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p. 7018 - 7028
(2021/11/17)
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- A CO2-mediated base catalysis approach for the hydration of triple bonds in ionic liquids
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Herein, we report a CO2-mediated base catalysis approach for the activation of triple bonds in ionic liquids (ILs) with anions that can chemically capture CO2 (e.g., azolate, phenolate, and acetate), which can achieve hydration of triple bonds to carbonyl chemicals. It is discovered that the anion-complexed CO2 could abstract one proton from proton resources (e.g., IL cation) and transfer it to the CN or CC bonds via a six-membered ring transition state, thus realizing their hydration. In particular, tetrabutylphosphonium 2-hydroxypyridine shows high efficiency for hydration of nitriles and CC bond-containing compounds under a CO2 atmosphere, affording a series of carbonyl compounds in excellent yields. This catalytic protocol is simple, green, and highly efficient and opens a new way to access carbonyl compounds via triple bond hydration under mild and metal-free conditions.
- Han, Buxing,Ke, Zhengang,Li, Ruipeng,Liu, Zhimin,Tang, Minhao,Wang, Yuepeng,Zeng, Wei,Zhang, Fengtao,Zhao, Yanfei
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supporting information
p. 9870 - 9875
(2021/12/27)
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- Molecular-docking-guided design and synthesis of new IAA-tacrine hybrids as multifunctional AChE/BChE inhibitors
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A series of new indole-3-acetic acid (IAA)-tacrine hybrids as dual acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitors were designed and prepared based on the molecular docking mode of AChE with an IAA derivative (1a), a moderate AChE inhibitor identified by screening our compound library for anti-Alzheimer's disease (AD) drug leads. The enzyme assay results revealed that some hybrids, e.g. 5d and 5e, displayed potent dual in vitro inhibitory activities against AChE/BChE with IC50 values in low nanomolar range. Molecular modeling studies in tandem with kinetic analysis suggest that these hybrids target both catalytic active site and peripheral anionic site of cholinesterase (ChE). Molecular dynamic simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) calculations indicate that 5e has more potent binding affinity than hit 1a, which may explain the stronger inhibitory effect of 5e on AChE. Furthermore, their predicted pharmacokinetic properties and in vitro influences on mouse brain neural network electrical activity were discussed. Taken together, compound 5e can be highlighted as a lead compound worthy of further optimization for designing new anti-AD drugs.
- Cheng, Zhi-Qiang,Zhu, Kong-Kai,Zhang, Juan,Song, Jia-Li,Muehlmann, Luis Alexandre,Jiang, Cheng-Shi,Liu, Chang-Liang,Zhang, Hua
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p. 277 - 288
(2018/11/06)
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- [18F]MALEIMIDE-BASED GLYCOGEN SYNTHASE KINASE-3BETA LIGANDS FOR POSITRON EMISSION TOMOGRAPHY IMAGING AND RADIOSYNTHESIS METHOD
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The present invention provides a compound having the structure: (Formula I), and a method of inhibiting Glycogen synthase kinase-3 β (GSK-3β) in a subject comprising administering to the subject said compound, so as to thereby inhibit the GSK-3β in the subject.
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Page/Page column 67; 68
(2018/08/03)
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- Corresponding amine nitrile and method of manufacturing thereof
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The invention relates to a manufacturing method of nitrile. Compared with the prior art, the manufacturing method has the characteristics of significantly reduced using amount of an ammonia source, low environmental pressure, low energy consumption, low production cost, high purity and yield of a nitrile product and the like, and nitrile with a more complex structure can be obtained. The invention also relates to a method for manufacturing corresponding amine from nitrile.
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Paragraph 0138; 0139; 0140; 0143; 0144
(2018/05/07)
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- Development of [18F]Maleimide-Based Glycogen Synthase Kinase-3β Ligands for Positron Emission Tomography Imaging
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Dysregulation of glycogen synthase kinase-3β (GSK-3β) is implicated in the pathogenesis of neurodegenerative and psychiatric disorders. Thus, development of GSK-3β radiotracers for positron emission tomography (PET) imaging is of paramount importance, because such a noninvasive imaging technique would allow better understanding of the link between the activity of GSK-3β and central nervous system disorders in living organisms, and it would enable early detection of the enzyme’s aberrant activity. Herein, we report the synthesis and biological evaluation of a series of fluorine-substituted maleimide derivatives that are high-affinity GSK-3β inhibitors. Radiosynthesis of a potential GSK-3β tracer [18F]10a is achieved. Preliminary in vivo PET imaging studies in rodents show moderate brain uptake, although no saturable binding was observed in the brain. Further refinement of the lead scaffold to develop potent [18F]-labeled GSK-3 radiotracers for PET imaging of the central nervous system is warranted.
- Hu, Kongzhen,Patnaik, Debasis,Collier, Thomas Lee,Lee, Katarzyna N.,Gao, Han,Swoyer, Matthew R.,Rotstein, Benjamin H.,Krishnan, Hema S.,Liang, Steven H.,Wang, Jin,Yan, Zhiqiang,Hooker, Jacob M.,Vasdev, Neil,Haggarty, Stephen J.,Ngai, Ming-Yu
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p. 287 - 292
(2017/03/17)
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- Direct reductive coupling of indoles to nitrostyrenes en route to (indol-3-yl)acetamides
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A highly efficient one-pot method for the reductive coupling of indoles to nitrostyrenes in polyphosphoric acid doped with PCl3 was developed. This method allows direct and expeditious access to primary (indol-3-yl)acetamides, interesting as anti-cancer drug candidates.
- Aksenov, Alexander V.,Aksenov, Nicolai A.,Dzhandigova, Zarema V.,Aksenov, Dmitrii A.,Voskressensky, Leonid G.,Nenajdenko, Valentine G.,Rubin, Michael
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p. 93881 - 93886
(2016/10/22)
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- Screening of NOS activity and selectivity of newly synthesized acetamidines using RP-HPLC
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Nitric Oxide Synthase (NOS) inhibitors could play a powerful role in inflammatory and neurodegenerative diseases. In this work, novel acetamidine derivatives of NOS were synthesized and the inhibitor activity was evalued. To screen the activity and selectivity, the l-citrulline residue, after the enzymatic NOS assay, was derivatized with o-phthaldialdehyde/N-acetyl cysteine (OPA/NAC) and then evaluated by RP-HPLC method with fluorescence detection.All compounds did not affect the activity of endothelial and neuronal isoforms, while nine of them possessed a percentage of iNOS activity at 10 μM lower than 50%, and were selected for IC50 evaluation. Among them, a compound emerged as a very potent (IC50 of 53 nM) and selective iNOS inhibitor.
- Fantacuzzi, Marialuigia,Maccallini, Cristina,Di Matteo, Mauro,Ammazzalorso, Alessandra,Bruno, Isabella,De Filippis, Barbara,Giampietro, Letizia,Mollica, Adriano,Amoroso, Rosa
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p. 419 - 424
(2016/02/16)
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- Biotransformation of Indole to 3-Methylindole by Lysinibacillus xylanilyticus Strain MA
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An indole-biotransforming strain MA was identified as Lysinibacillus xylanilyticus on the basis of the 16S rRNA gene sequencing. It transforms indole completely from the broth culture in the presence of an additional carbon source (i.e., sodium succinate). Gas-chromatography-mass spectrometry identified indole-3-acetamide, indole-3-acetic acid, and 3-methylindole as transformation products. Tryptophan-2-monooxygenase activity was detected in the crude extracts of indole-induced cells of strain MA, which confirms the formation of indole-3-acetamide from tryptophan in the degradation pathway of indole. On the basis of identified metabolites and enzyme assay, we have proposed a new transformation pathway for indole degradation. Indole was first transformed to indole-3-acetamide via tryptophan. Indole-3-acetamide was then transformed to indole-3-acetic acid that was decarboxylated to 3-methylindole. This is the first report of a 3-methylindole synthesis via the degradation pathway of indole.
- Arora, Pankaj Kumar,Dhar, Kartik,Veloz García, Rafael Alejandro,Sharma, Ashutosh
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- Selective aerobic hydrolysis of nitriles to amides using cobalt(II)/zinc
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A novel protocol has been developed for the aerobic hydrolysis of nitriles to amides using cobalt(II)/zinc without using any strong acids and bases under solvent-free conditions. The reaction showed good performance for benzonitriles with sensitive groups such as ester and carboxylic acid.
- Keshipour, Sajjad,Shaabani, Ahmad
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p. 5071 - 5078
(2015/07/08)
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- Synthesis and in-vitro anticancer activity of 3,5-bis(indolyl)-1,2,4- thiadiazoles
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A series of 3,5-bis(indolyl)-1,2,4-thiadiazoles were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. The reaction of indole-3-thiocarboxamide 3 with iodobenzene diacetate underwent oxidative dimerization to give 3,5-bis(indolyl)-1,2,4-thiadiazoles 4a-n. Among the synthesized bis(indoly)-1,2,4-thiadiazoles, the compound 4h with 4-chlorobenzyl and methoxy substituents showed the most potent activity.
- Kumar, Dalip,Kumar, N. Maruthi,Chang, Kuei-Hua,Gupta, Ritika,Shah, Kavita
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scheme or table
p. 5897 - 5900
(2011/10/18)
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- Ceric ammonium nitrate (CAN) promoted efficient solid phase synthesis of amide derivatives: A green approach
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Ceric ammonium nitrate (CAN) has been found to be an efficient catalyst for the solid phase synthesis of amide derivatives of a wide range of substituted carboxylic acids and urea in excellent yields under microwave irradiation conditions. High yields are achieved even on a gram scale, while reaction times are considerably shortened. This method displays both economic and environmental advantages.
- Reddy, Ch. Sanjeeva,Raghu,Nagaraj
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p. 315 - 318
(2008/09/20)
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- Aryl-indolyl maleimides as inhibitors of CaMKIIδ. Part 2: SAR of the amine tether
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A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin-dependant kinase. Inhibitory activities against the enzyme ranged from 34 nM to >20 μM and were dependant upon both the nature of the aryl group and the tether joining the basic amine to the indolyl maleimide core. Key interactions with the kinase ATP site and hinge region, predicted by homology modeling, were confirmed.
- Levy, Daniel E.,Wang, Dan-Xiong,Lu, Qing,Chen, Zheng,Perumattam, John,Xu, Yong-jin,Higaki, Jeffrey,Dong, Hanmin,Liclican, Albert,Laney, Maureen,Mavunkel, Babu,Dugar, Sundeep
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p. 2395 - 2398
(2008/09/20)
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- Aryl-indolyl maleimides as inhibitors of CaMKIIδ. Part 1: SAR of the aryl region
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A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin dependant kinase. Inhibitory activities against the enzyme ranged from 34 nM to >20 μM and were dependant upon both the nature of the aryl group and the hydrogen bond donating potential of the maleimide ring. Key interactions with the kinase ATP site and hinge region were found to be consistent with homology modeling predictions.
- Levy, Daniel E.,Wang, Dan-Xiong,Lu, Qing,Chen, Zheng,Perumattam, John,Xu, Yong-jin,Liclican, Albert,Higaki, Jeffrey,Dong, Hanmin,Laney, Maureen,Mavunkel, Babu,Dugar, Sundeep
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p. 2390 - 2394
(2008/09/21)
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- Microwave assisted synthesis of novel 1,2,4-triazines in dry media
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An efficient facile and solventless synthesis of 1,2,4-triazines using microwave is described. A non conventional synthetic procedure has been developed where solid inorganic support is used as energy transfer medium under microwave irradiation (MWI) which devoids hazards of solution phase reactions. The reaction time has been brought down from hours to seconds with improved yield as compared to conventional heating.
- Kidwai,Sapra,Bhushan,Misra
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p. 1639 - 1645
(2007/10/03)
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- A Novel Enzyme, L-Tryptophan Oxidase, from a Basidiomycete, Coprinus sp. SF-1: Purification and Characterization
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A basidiomycete, Coprinus sp. SF-1, was found to produce an L-Trp-oxidizing enzyme by screening from the culture collection of our laboratory. After solubilization by 1 M NaSCN from the participate fraction of disrupted cells of the strain, the enzyme was purified about 76-fold to essential homogeneity. The enzyme had a molecular mass of about 420 kDa and the subunit molecular mass was 68 kDa. The enzyme contained 1 mol of non-covalently bound FAD per mol of the subunit. It catalyzed the simultaneous reactions of oxidative deamination and oxygenative decarboxylation of L-Trp to form indolepyruvic acid and indole-3-acetamide, the former of which was further oxidized to indole-3-acetic acid. The molar ratio of the respective reaction products was about 9:1. The enzyme specifically oxidized L-Trp, and slightly acted on L-Phe and L-Tyr. The Km for L-Trp was about 0.5 mM in both oxidase and oxygenase reactions. Thus, the enzyme is a novel one and was tentatively designated L-Trp oxidase (deaminating and decarboxylating) . The optimum pHs of oxidase and oxygenase activities were 7.0 and 9.0, respectively. The optimum temperatures of both activities were 50°C. The enzyme was stable at pH 6.0-10.5 and below 50°C, and at 4°C for 1 year.
- Furuya, Yuji,Sawada, Hidemi,Hirahara, Toshikatsu,Ito, Kazue,Ohshiro, Takashi,Izumi, Yoshikazu
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p. 1486 - 1493
(2007/10/03)
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- Polyamines and polypeptides useful as antagonists of excitatory amino acid neuro-transmitters and/or as blockers of calcium channels
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This invention relates to certain polyamines and polypeptides found to be present in the venom of the Agelenopsis aperta spider. The polyamines of this invention and the salts thereof antagonize excitatory amino acid neurotransmitters, which neurotransmitters affect cells of various organisms and are useful in antagonizing said neurotransmitters, per se, in the treatment of excitatory amino acid neurotransmitter mediated diseases and conditions and in the control of invertebrate pests. The polypeptides of this invention and one of said polyamines and the salts thereof block calcium channels in cells of various organisms and are useful in blocking said calcium channels in cells, per se, in the treatment of calcium channel mediated diseases and conditions and in the control of invertebrate pests. This invention also relates to compositions comprising said polyamines, polypeptides and salts thereof.
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- SYNTHESIS OF VARIOUS AROMATIC AMIDE DERIVATIVES USING NITRILE HYDRATASE OF RHODOCOCCUS RHODOCHOROUS J1
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Nitrile hydratase, that is produced abundantly in cells of Rhodococcus rhodochorous J1, catalyses the conversion of various aromatic nitrile derivatives to the corresponding amides.Using Rh. rhodochorous J1 resting cells, the conditions for the production of benzamide, 2,6-difluorobenzamide, indolacetamide, thiophenecarboxamide and furanecarboxamide were optimized.Under the determined conditions, 489 g of benzamide, 306 g of 2,6-difluorobenzamide, 1045 g of 3-indoleacetamide, 210 g of 2-thiophenecarboxamide and 522 g of 2-furanecarboxamide were produced, with 100percent molar conversion, from the corresponding nitriles, per litre of reaction mixture.
- Mauger, Jacques,Nagasawa, Toru,Yamada, Hideaki
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p. 1347 - 1354
(2007/10/02)
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- A GENERAL METHOD FOR THE SYNTHESIS OF INDOLES BEARING A VARIETY OF SUBSTITUENTS AT THE β-POSITION, AND ITS APPLICATION TO THE SYNTHESIS OF L-TRYPTOPHAN
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A general synthetic method of β-substituted indoles such as indolacetic acid, tryptamine and L-tryptophan has been exploited utilizing α-methoxylated amides, lactams, a carbamate, and sulfonamides, easily obtainable by an electrochemical method, as key intemediates.
- Shono, Tatsuya,Matsumura, Yoshihiro,Kanazawa, Takenobu
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p. 1259 - 1262
(2007/10/02)
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- SYNTHESIS AND PROPERTIES OF AZOLES AND THEIR DERIVATIVES. 32. SYNTHESIS AND SOME TRANSFORMATIONS OF HYDROCHLORIDES OF IMIDO ESTERS OF INDOLECARBOXYLIC ACIDS
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The Pinner reaction with the nitriles of indole-3-carboxylic and 3-indolylacetic acids was studied.The hydrochlorides of the imide esters of these acids, which were converted to the free bases, amides, and esters, were synthesized.Imidazolines, benzimidazoles, and benzoxazoles that contain indole substituents were obtained by condensation of the hydrochlorides of the imido esters of the indolecarboxylic acids with ethylenediamine, o-phenylenediamine, and o-aminophenol.
- Kelarev, V. I.,Shvekhgeimer, G. A.
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p. 501 - 506
(2007/10/02)
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