- QUINUCLIDINES FOR MODULATING ALPHA 7 ACTIVITY
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Provided are substituted quinuclidine compounds, pharmaceutical compositions comprising such compounds, and methods of modulating α7 nicotinic acetylcholine receptors and treating neurological disorders using such compounds.
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Paragraph 0370; 0371
(2016/02/29)
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- Novel Anthranilic Diamide Scaffolds Containing N-Substituted Phenylpyrazole as Potential Ryanodine Receptor Activators
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To discover potent insecticides targeting ryanodine receptors (RyRs), a series of novel anthranilic diamides analogues (12a-12u) containing N-substituted phenylpyrazole were designed and synthesized. These compounds were characterized by 1H NMR, 13C NMR, and HRMS, and the structure of compound 12u was confirmed by X-ray diffraction. Their insecticidal activities indicated that these compounds displayed moderate to excellent activities. In particular, 12i showed 100 and 37% larvicidal activities against oriental armyworm (Mythimna separata) at 0.25 and 0.05 mg L-1, equivalent to that of chlorantraniliprole (100%, 0.25 mg L-1; and 33%, 0.05 mg L-1). The activity of 12i against diamondback moth (Plutella xylostella) was 95% at 0.05 mg L-1, whereas the control was 100% at 0.05 mg L-1. The calcium-imaging technique experiment results showed that the effects of 12i on the intracellular calcium ion concentration ([Ca2+]i) in neurons were concentration-dependent. After the central neurons of Helicoverpa armigera were dyed by loading with fluo-5N and treated with 12i, the free calcium released in endoplasmic reticulum indicated the target of compound 12i is RyRs or IP3Rs. The activation of RyRs by natural ryanodine completely blocked the calcium release induced by 12i, which indicated that RyRs in the central neurons of H. armigera third-instar larvae is the possible target of compound 12i.
- Liu, Jing-Bo,Li, Yu-Xin,Zhang, Xiu-Lan,Hua, Xue-Wen,Wu, Chang-Chun,Wei, Wei,Wan, Ying-Ying,Cheng, Dan-Dan,Xiong, Li-Xia,Yang, Na,Song, Hai-Bin,Li, Zheng-Ming
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p. 3697 - 3704
(2016/06/01)
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- SUBSTITUTED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
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The present disclosure relates to pyrimidine compounds of formula (I), their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to process of preparation of these pyrimidine compounds, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases and disorders mediated by epidermal growth factor receptor (EGFR) family kinases.
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Paragraph 00069
(2015/03/13)
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- Trichloroisocyanuric acid in 98% sulfuric acid: A superelectrophilic medium for chlorination of deactivated arenes
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Trichloroisocyanuric acid (TCCA) reacts with arenes and its reactivity is highly affected by the acid strength of the reaction medium. Deactivated arenes are efficiently chlorinated by TCCA in H2SO4. Our results, along with DFT calculations and 13C NMR spectrometry suggest the formation of a monoprotonated TCCA superelectrophile as the reactive species that can efficiently transfer electrophilic Cl+ to even very weak nucleophiles, such as m-dinitrobenzene.
- Mendo?a, Gabriela Fonseca,Senra, M?nica Rufino,Esteves, Pierre M.,De Mattos, Marcio C.S.
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experimental part
p. 176 - 181
(2012/04/04)
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- PROTEIN KINASE C INHIBITORS AND USES THEREOF
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This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
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Page/Page column 64
(2011/06/23)
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- NEW SUBSTITUTED ARYLSULPHONYLGLYCINES, THE PREPARATION THEREOF AND THE USE THEREOF AS PHARMACEUTICAL COMPOSITIONS
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The present invention relates to substituted arylsulphonylglycines of general formula (I) wherein R, X, Y and Z are defined as in claim 1, the tautomers, enantiomers, diastereomers, mixtures thereof and salts thereof, which have valuable pharmacological properties, particularly the suppression of the interaction of glycogen phosphorylase a with the GL subunit of glycogen-associated protein phosphatase 1 (PP1 ), and their use as pharmaceutical compositions.
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Page/Page column 109-110
(2008/12/07)
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- Efficient one-pot transformation of aminoarenes to haloarenes using halodimethylisulfonium halides generated in situ
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Halodimethylsulfonium halide 1, which is readily formed in situ from hydrohaloic acid and DMSO, is a good nucleophilic halide. This activated nucleophilic halide rapidly converts aryldiazonium salt prepared in situ by the same hydrohaloic acid and nitrite ion to aryl chlorides, bromides, or iodides in good yield. The combined action of nitrite ion and hydrohaloic acid in DMSO is required for the direct transformation of aromatic amines, which results in the production of aryl halides within 1 h. Substituted compounds with electron-donating or -withdrawing groups or sterically hindered aromatic amines are also smoothly transformed to the corresponding aromatic halides. The only observed by-product is the deaminated arene (usually 7%). The isolated aryldiazonium salts can also be converted to the corresponding aryl halides using 1. The present method offers a facile, one-step procedure for transforming aminoarenes to haloarenes and lacks the environmental pollutants that usually accompany the Sandmeyer reaction using copper halides.
- Baik, Woonphil,Luan, Wanqiang,Lee, Hyun Joo,Yoon, Cheol Hun,Koo, Sangho,Kim, Byeong Hyo
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p. 213 - 219
(2007/10/03)
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- Small molecules useful in the treatment of inflammatory disease
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Novel compounds of the formula I which are useful for treating or preventing inflammatory and immune cell-mediated diseases. Exemplary compounds are: 5-(R)-(4-bromobenzyl)-3-(3-chloro-5-nitrophenyl)-5-methylimidazoline-2,4-dione; and, 5-(R)-(4-bromobenzyl
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Page column 28
(2010/02/05)
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- Electrophilic Aromatic Substitution. Part 35. Chlorination of 1,3-Dinitrobenzene, 1-Chloro-2,4-dinitrobenzene, and 2,4-Dinitrotoluene with Nitric Acid and Hydrogen Chloride or Chlorine in Sulphuric Acid or Oleum
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Solutions of sulphuric acid or oleum containing HCl or Cl2 and nitric acid have been found both to chlorinate and nitrate deactivated aromatic compounds.The kinetics and products of the chlorination of 1,3-dinitrobenzene and 1-chloro-2,4-dinitrobenzene in sulphuric acid or oleum containing HCl and nitric acid at 130 deg C, and the kinetics and products of the chlorination of 2,4-dinitrotoluene at 90 deg C in sulphuric acid or oleum containing Cl2 and nitric acid, are reported. 1,3-Dinitrobenzene and 1-chloro-2,4-dinitrobenzene were predominantly chlorinated. 2,4-Dinitrotoluene gave approximately equal amounts of 6-chloro-2,4-dinitrotoluene and 2,4,6-trinitrotoluene.The results show that under these conditions, chlorination and nitration are competing electrophilic reactions, and that chlorination is less selective than nitration.Possible mechanisms for chlorination are discussed.
- Melhuish, Martin W.,Moodie, Roy B.
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p. 667 - 674
(2007/10/02)
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- Nitrosations in Anhydrous Trifluoroacetic Acid Media: A Modification for Insoluble or Deactivated Amine and Amide Precursors
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Nitrosation reactions with sodium nitrite can be accomplished cleanly in anhydrous trifluoroacetic acid as solvent, which permits the use of both deactivated and insoluble primary amines and amides as starting materials.
- Kanakarajan, K.,Haider, Karl,Czarnik, Anthony W.
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p. 566 - 568
(2007/10/02)
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- Substituent Effects on the Decarboxylation of Dinitrobenzoate Ions, Representative Aromatic SE1 Reactions
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Kinetics of decarboxylation, in water solution, of several 4-substituted 2,6-dinitrobenzoic and 2-substituted 4,6-dinitrobenzoic acids were determined, at several temperatures.The reactions are first order at the low concentrations employed, at which the acids are fully dissociated.Decarboxylation is accelerated by electron-attracting substituents; the Hammett ρ for the effects of 4-substituents is about +2.6.All the decarboxylations involve large positive enthalpies and entropies of activation.The solvent kinetic isotope effect (D2O/H2O) is not significantly different from unity.The data support a mechanism where in the substituted benzoate ion loses CO2 in the rate-determining step, forming a substituted aryl anion, which is then rapidly hydronated by the solvent.In the case of 2-methoxy-4,6-dinitrobenzoate ion, reaction occured with strikingly different activation parameters.
- Segura, Pascual,Bunnett, Joseph F.,Villanova, Laura
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p. 1041 - 1045
(2007/10/02)
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- Electrophilic Aromatic Substitution. Part 32. The Nitration of 1,3,5-Trichloro-2-nitrobenzene, 1,3,5-Trichloro-2,6-dinitrobenzene, and 1,2,3,5-Tetrachloro-4,6-dinitrobenzene in Sulphuric Acid and in Oleum
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The kinetics of nitration of 1,3,5-trichloro-2-nitrobenzene (TCNB) in sulphuric acid and in oleum at 25, 50, and 75 deg C, and of 1,3,5-trichloro-2,4-dinitrobenzene (TCDNB) in oleum at 150 deg C have been measured. 1,2,3,5-Tetrachloro-4,6-dinitrobenzene (TetCDNB) reacts with nitric acid in sulphuric acid and in oleum at 150 deg C; the rate profile for the reaction shows a nitration process to be occuring.From TCNB in sulphuric acid the yield of TCDNB was not quite quantitative and at 25 deg C in oleum a small amount of 1,2,3,5-tetrachloro-4-nitrobenzene was also formed.TCDNB gave a mixture of TCTNB (the major product) and TetCDNB in proportions which varied with acidity; lower acidities were more favourable to the formation of TetCDNB.The total amount of chlorine present in the TCDNB, TCTNB, and TetCDNB was equal to that present in the TCDNB at the start of the reaction.The nitration of TetCDNB in sulphuric acid at 150 deg C gave carbon dioxide and hydrogen chloride, and some sulphur dioxide and nitric oxide or nitrogen dioxide.In the nitration of TCDNB this compound produces the chlorinating agent and reacts with it to give TetCDNB.The chlorinating agent can chlorinate added 1,3-dinitrobenzene.The use of H(15)NO3 in the nitration TCDNB leads to (15)N-incorporation in it and in the TetCDNB produced.Separate nitration of TetCDNB causes only slight (15)N-incorporation into it.It is suggested that in addition to the main route of nitration leading to TCTNB, the nitration of TCDNB gives an ipso-Wheland intermediate by attack of nitronium ion at a nitrated position; this intermediate may either return to starting material or give a diene by nucleophilic capture.Decomposition of the diene gives hydrogen chloride or chloride anion which is oxidised by nitric acid to an electrophilic chlorinating agent.
- Moodie, Roy B.,Payne, Malcolm A.,Schofield, Kenneth
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p. 1457 - 1464
(2007/10/02)
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- Process for the production of nitro derivatives of aromatic compounds
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Nitroderivates of aromatic compounds which are difficult to nitrate, can readily be obtained by nitration providing that the aromatic compound is treated with nitric acid or another nitrating agent in the presence of aliphatic or cycloaliphatic hydrocarbons monosubstituted or polysubstituted by halogen, the nitro group or an alkyl sulphonyl group, and the nitro derivative formed subsequently isolated.
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