- Synthesis and in vitro evaluation of neutral aryloximes as reactivators of Electrophorus eel acetylcholinesterase inhibited by NEMP, a VX surrogate
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Casualties caused by nerve agents, potent acetylcholinesterase inhibitors, have attracted attention from media recently. Poisoning with these chemicals may be fatal if not correctly addressed. Therefore, research on novel antidotes is clearly warranted. Pyridinium oximes are the only clinically available compounds, but poor penetration into the blood-brain barrier hampers efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in SAR studies, we synthesized and evaluated neutral aryloximes as reactivators for acetylcholinesterase inhibited by NEMP, a VX surrogate. Although few tested compounds reached comparable reactivation results with clinical standards, they may be considered as leads for further optimization.
- Cavalcante, Samir F. de A.,Kitagawa, Daniel A.S.,Rodrigues, Rafael B.,Bernardo, Leandro B.,da Silva, Thiago N.,dos Santos, Wellington V.,Correa, Ana Beatriz de A.,de Almeida, Joyce S.F.D.,Fran?a, Tanos C.C.,Ku?a, Kamil,Simas, Alessandro B.C.
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- ADENOSINE RECEPTOR ANTAGONISTS AND USES THEREOF
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Disclosed herein are compounds, compositions, formulations, and methods for modulating the A2B adenosine receptor.
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Paragraph 00307; 00308
(2019/10/01)
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- Reactivity of [WCl6] with Ethers: A Joint Computational, Spectroscopic and Crystallographic Study
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The reactions of [WCl6] with a series of ethers have been performed in chlorinated solvent and elucidated by means of analytical, spectroscopic and DFT methods. The addition of tetrahydropyran (thp) or 1,4-dioxane to [WCl6] resulted in the reversible formation of the adducts WCl6···L [L = thp (1a), 1,4-dioxane (1b)], detected in solution by NMR spectroscopy. The reaction of [WCl6] with thp in a molar ratio of 1:2 in chloroform at reflux afforded [WOCl4(thp)] (2a), which was isolated in 51 % yield. [WOCl4(OMe2)] (2b) and [WOCl3(OMe2)2] (3a) were isolated in yields of 53 and 18 %, respectively, from the reaction of [WCl6] with an excess of dimethyl ether. [WOCl3(OEt2)2] (3b) was the only identified metal compound produced from the reaction of [WCl6] and OEt2(1:2 molar ratio). According to NMR studies, the oxide ligand in 2a,b and 3a,b was generated by double C–O bond cleavage involving one equivalent of organic reactant. The 1:1 reaction of [WCl6] with 1,2-diethoxyethane led to [WCl5(κ1-OCH2CH2OEt)] (4) and a minor amount of [WCl4(κ2-EtOCH2CH2OEt)] (5). The aryl oxide compound [WCl5(OPh)] (6) was prepared in 62 % yield from the reaction of [WCl6] and anisole by selective Csp3–O bond activation. The prolonged heating of a mixture of [WCl6] and diphenyl ether in 1,2-dichloroethane led to the isolation of the WVcomplex [WCl5(OPh2)] (7). The molecular structures of 2a and 3a were ascertained by X-ray diffraction.
- Bortoluzzi, Marco,Marchetti, Fabio,Pampaloni, Guido,Zacchini, Stefano
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p. 3169 - 3177
(2016/07/14)
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- GLYCOSIDE COMPOUND, METHOD FOR PRODUCING THIOETHER, ETHER, METHOD FOR PRODUCING ETHER, METHOD FOR PRODUCING GLYCOSIDE COMPOUND, METHOD FOR PRODUCING NUCLEIC ACID
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Provided is a glucoside compound, which is capable of providing a phosphoramidite, which can be produced at a low cost and can produce a nucleic acid in a high yield and with high purity. A glycoside compound represented by the following chemical formula (1). In the chemical formula (1), B is an atomic group having a nucleic acid base skeleton, and optionally having a protecting group, R1 and R2 are each a hydrogen atom or a protecting group, or R1 and R2 in conjunction optionally form an atomic group represented by the following chemical formula (R1R2A) or (R1R2B): each R1a is a hydrogen atom, a straight chain or branched alkyl group and the like, L1 is an unsubstituted or alkyl-substituted ethylene group, R3 is a group represented by the following chemical formula (R3): in the chemical formula (R3), n is a positive integer, and [D1] is an electron-withdrawing group.
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Paragraph 0154; 0155; 0156
(2014/07/09)
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- Synthesis of oligoribonucleotides with phosphonate-modified linkages
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Solid phase synthesis of phosphonate-modified oligoribonucleotides using 2′-O-benzoyloxymethoxymethyl protected monomers is presented in both 3′→5′ and 5′→3′ directions. Hybridisation properties and enzymatic stability of oligoribonucleotides modified by regioisomeric 3′- and 5′-phosphonate linkages are evaluated. The introduction of the 5′-phosphonate units resulted in moderate destabilisation of the RNA/RNA duplexes (ΔTm -1.8 °C/mod.), whereas the introduction of the 3′-phosphonate units resulted in considerable destabilisation of the duplexes (ΔTm -5.7 °C/mod.). Molecular dynamics simulations have been used to explain this behaviour. Both types of phosphonate linkages exhibited remarkable resistance in the presence of ribonuclease A, phosphodiesterase I and phosphodiesterase II.
- Pav, Ondej,Koiova, Ivana,Barvik, Ivan,Pohl, Radek,Budinsky, Milo,Rosenberg, Ivan
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supporting information; experimental part
p. 6120 - 6126
(2011/10/10)
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- A systematic study on the activation of simple polyethers by MoCl 5 and WCl6
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MoCl5, 1a, and WCl6, 1b, activate 1,3-dioxolane at room temperature in chlorinated solvents: the compound [MoOCl 3{OC(H)OCH2CH2Cl}]2, 2, has been isolated from MoCl5/dioxolane. The mixed oxo-chloro species WOCl 4, 1c, reacts with 1,3-dioxolane, selectively giving the coordination adduct WOCl4(κ1-C3H6O 2), 3. Dimethoxymethane, CH2(OMe)2, undergoes activation including C-H bond cleavage when reacted with 1a to give the molybdenum complexes [MoOCl3{OC(H)OMe}]2, 4, and Mo 2Cl5(OMe)5, 5. The reactions of 1b with CH 2(OR)2 (R = Me, Et) proceed via O-abstraction with formation of the oxo-derivatives WOCl4[O(R)CH2Cl] (R = Me, 6a; R = Et, 6b) in admixture with equimolar amounts of RCl. The reactions of 1a,b with CMe2(OMe)2 lead to mesityl oxide, MeC(O)CHC(Me)2. A series of simple diethers of general formula ROCH2(CHR′)OR′′ are activated by 1a,b in CDCl 3, usually via cleavage of C-O bonds at high temperature. The complex WCl5(OCH2CH2OMe), 7, has been detected in solution as an intermediate species in the course of the degradation of 1,2-dimethoxyethane (dme) by 1b. The activation of CH(OMe)3 by 1 is limited to C-O bonds and selectively gives methyl chloride and methylformate, which has been found coordinated in WOCl4[OC(H)OMe], 8. The organic fragments produced in the reactions have been detected by GC-MS and NMR analyses, upon hydrolysis of the reaction mixtures. Compounds 2 and 5, which have had their molecular structures ascertained by X-ray diffraction, represent rare examples of crystallographically-characterized dinuclear Mo(v) species containing both halides and oxygen ligands.
- Dolci, Sara,Marchetti, Fabio,Pampaloni, Guido,Zacchini, Stefano
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experimental part
p. 5367 - 5376
(2010/08/04)
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- Process for halomethyl ethers of hydroxyiminomethyl quaternary pyridinium salts
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A halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropane is prepared by adding a pyridinealdoxime to a bis-halomethylether in such a manner that the bis-halomethylether is maintained in excess throughout the addition. This procedure produces the halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropane in high yield and purity, which facilitates its use as an intermediate in the manufacture of an asymmetrically substituted 1,3-di (1-pyridino)-2-oxapropane, a class of compounds that are generally useful antidotes to various toxic agents. A prominent member of the class is the dimethylsulfonate salt of 1-(2-hydroxyiminomethyl-1-pyridino)-3-(4-carbamoyl-1-pyridino)-2-oxapropane. The use of mercaptoalkyl-functionalized polymers is disclosed as a preferred metal ion scavenger for a final purification step in the manufacture of these compounds.
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Page/Page column 6
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF CHLOROMETHYL 2,2,2-TRIFLUORO-1-(TRIFLUOROMETHYL) ETHYL ETHER
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The present invention refers to a process for the preparation of chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether (sevochlorane), which consists of reacting hexafluoroisopropanol with: a formaldehyde equivalent selected between paraformaldehyde or 1,3,5-trioxane, a chlorinating agent selected from the group consisting of oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, sulfuryl chloride and thionyl chloride, and a strong acid selected from the group consisting of concentrated or fuming sulfuric acid. Said process provides sevochlorane in high purity and yield, which can be converted to sevoflurane by known means.
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Page/Page column 17-21
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF FLUOROMETHYL 2,2,2-TRIFLUORO-1-(TRIFLUOROMETHYL) ETHYL ETHER
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The present invention refers to a process for the preparation of fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether (sevoflurane) which includes a step that consists of reacting hexafluoroisopropanol with a formaldehyde equivalent selected among paraformaldehyde or 1,3,5-trioxane, a chlorinating agent selected from the group consisting of oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, sulfuryl chloride and thionyl chloride, and a strong acid selected from the group consisting of concentrated or fuming sulfuric acid resulting in the formation of the intermediate sevochlorane which is converted to sevoflurane in a second step which consists of reacting sevochlorane with an alkali metal fluoride, or a linear or branched chain tetra-alkyl quarternary ammonium fluoride in the presence of a sub-stoichiometric quantity of an alkali metal iodide, or a linear or branched alkyl chain tetra-alkyl quarternary ammonium iodide, preferably in a solvent.
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Page/Page column 20-22
(2008/06/13)
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- Process for halomethyl ethers of hydroxyiminomethyl quaternary pyridinium salts
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A halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropane is prepared by adding a pyridinealdoxime to a bis-halomethylether in such a manner that the bis-halomethylether is maintained in excess throughout the addition. This procedure produces the halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropane in high yield and purity, which facilitates its use as an intermediate in the manufacture of an asymmetrically substituted 1,3-di (1-pyridino)-2-oxapropane, a class of compounds that are generally useful antidotes to various toxic agents. A prominent member of the class is the dimethylsulfonate salt of 1-(2-hydroxyiminomethyl-1-pyridino)-3-(4-carbamoyl-1-pyridino)-2-oxapropane. The use of mercaptoalkyl-functionalized polymers is disclosed as a preferred metal ion scavenger for a final purification step in the manufacture of these compounds.
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Page/Page column 4
(2008/06/13)
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- Enantiomerically pure 2-aminopurine phosphonate nucleotide analogs as antiviral agents
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Cyclic and acyclic 2-aminopurine phosphonate nucleotide analogs useful to treat herpes viral infections are provided in enantiomerically pure form. Pharmaceutical compositions and methods for treating herpes viral infections are provided as well, as is a chiral synthesis for preparing the novel compounds in enantiomerically pure form.
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- NMR study of transformations of monochlorodimethyl ether in the presence of tin(IV) chloride
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Solutions of tin(IV) chloride in commercial monochlorodimethyl ether were studied by 1H and 13C NMR. Comparison of the spectra of these solutions with those of similar solutions of titanium tetrachloride used in production of anion exchangers allowed refining the scheme of side reactions of the components of the chloromethylating systems, affecting the characteristics of ion-exchange resins.
- Talzi,Ignashin
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p. 1832 - 1835
(2007/10/03)
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- Protected nucleoside and method for its synthesis
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The present invention relates to a nucleoside having the formula: STR1 where R1 is a hydrogen or a protecting group; R2 is a hydrogen or a coupling group; R3 and R4 are each either a hydrogen or an alkyl group, where R3 and R4 can be connected in a ring; R5 is a hydrogen, an alkyl group, or a carboxylic ester group; R6 is a hydrogen, an alkyl group, or a carboxylic ester group; R7 is a hydrogen, a nitro group, a halogen, a cyano group, or an alkyl group, where R7 is attached at either position 4, 5 or 6; and Base is a protected heterocyclic base. Further, the present invention relates to a method of making the nucleoside and a method of oligomer synthesis utilizing the nucleoside.
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- Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
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Oligonucleotide analogs having one or more substitute linkages of the formula 2'/3'--S--CH2 --CH=5' or 2'/3'--O--CH2 --CH=5' between adjacent nucleomonomers are disclosed. The substitute linkage replace the usual phosphodiester linkage found in unmodified nucleic acids. The oligonucleotide analogs are easy to synthesize, stable in vivo, resistant to endogenous nucleases and are able to hybridize to target nucleic acid sequences in a sequence specific manner.
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- Unambiguous synthesis of 2,4-diphenyl-3,7-dioxabicyclooctane
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2,4-Diphenyl-3,7-dioxabicyclooctane (3c) has been synthesized unambiguously by the reaction of 2,5-dihydro-2,5-diphenylfuran(6) with chloromethoxymethyllithium(5).Though the mass spectrum of 3c is identical with its 2,6-isomer(2c), there are small significant differences in their spectra.
- Jack, Ibiba R.
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p. 454 - 456
(2007/10/02)
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- Structural Studies on Bioactive Compounds. Part 7. The Design and Synthesis of &α-Substituted Serines as Prospective Inhibitors of Serine Hydroxymethyltransferase
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A short series of α-substituted analogues of serine, designed as enzyme-activated, irreversible inhibitors of serine hydroxymethyltransferase, has been prepared. (+/-)-α-Allyl- and (+/-)-α-prop-2-ynyl-serine were synthesised by appropriate alkylation of the anion derived from ethyl acetamidocyanoacetate, followed by selecttive reduction of the ester function and hydrolysis of protecting groups.Acetoxymethylation of the anion derived from methyl 2-(benzylideneamino)but-2-enoate gave (+/-)-α-vinylserine after deprotection.These novel analogues of serine were largely inactive as inhibitors of the enzyme, except that (+/-)-α-vinylserine showed weak competitive inhibition.
- Tendler, Saul J. B.,Threadgill, Michael D.,Tisdale, Michael J.
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p. 2617 - 2624
(2007/10/02)
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- Selective hydroformylation process
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This disclosure is concerned with the use of supported platinum halide, Group IVA metal halide catalysts suitable for the hydroformylation of α-olefin substrates to predominantly linear, straight-chain aldehydes.
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- (Alkynyloxy)alkyl and (alkenyloxy)alkyl carbamates and their use as herbicides
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This invention is novel (alkynyloxy)alkyl and (alkenyloxy)alkyl carbamates, which are highly effective herbicidal agents.
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