- Fluorination of aromatic compounds with N-fluorobenzenesulfonimide under solvent-free conditions
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Reactions of N-fluorobenzenesulfonimide with methylbenzenes, phenols, and phenol ethers were studied under solvent-free conditions. The rate constant ratio for the reactions with mesitylene and durene indicates polar mechanism of the process. Solvent-free fluorination of aromatic compounds with N-fluorobenzenesulfonimide in some cases is more selective than reactions with other N-F reagents in a solvent.
- Andreev,Borodkin,Shubin
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- 8-FLUORO-4-ALKYLUMBELLIFERYL ALPHA-D-GLUCOPYRANOSIDE, BIOLOGICAL STERILIZATION INDICATOR INCLUDING THE SAME AND ITS USE IN A METHOD OF DETERMINING EFFICACY OF A STERILIZATION PROCESS
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A self-contained biological sterilization indicator comprises: a housing; bacterial spores comprising, and/or capable of producing, an enzyme capable of catalyzing cleavage of an enzyme substrate; and a frangible container containing a composition, wherein the composition comprises the enzyme substrate, wherein if the frangible container is broken the composition will contact the bacterial spores to form a mixture having an initial pH in the range from 6.0 to 9.0. The enzyme substrate comprises a fluorinated 4'-alkylumbelliferyl α-D-glucopyranoside represented by the structural formula (I), wherein R is an alkyl group having from 1 to 12 carbon atoms. A biological sterilization indicator comprising a kit containing isolated components comprising (i) bacterial spores comprising, and/or capable of producing, an enzyme capable of catalyzing cleavage of the enzyme substrate and a method of assessing efficacy of a sterilization process are also disclosed.
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Page/Page column 53; 54
(2021/04/02)
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- ALPHA, BETA-UNSATURATED AMIDE COMPOUND
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An object of the present invention is to provide an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like. The α,β-unsaturated amide compound represented by the following formula (I) or a pharmaceutically acceptable salt or the like thereof has anticancer activity and the like: [wherein, "A" represents optionally substituted heterocyclic diyl, R1 represents hydrogen atom or optionally substituted lower alkyl, R2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents -O-, -S-, -SO2-, -NRX1- (wherein, RX1 represents hydrogen atom or lower alkyl), -CHRX2- (wherein, RX2 represents hydrogen atom or hydroxy), -CH=CH-, -CO- or -NH-CO-, and n1 and n2 are the same or different, and each represents 0 or 1].
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Paragraph 0624
(2020/12/10)
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- FLUORINATED 4' ALKYLUMBELLIFERYL α-D-GLUCOPYRANOSIDES, BIOLOGICAL STERILIZATION INDICATORS INCLUDING THE SAME AND METHODS OF USING THE SAME
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A self-contained biological sterilization indicator comprises: a housing; bacterial spores comprising, and/or capable of producing, an enzyme capable of catalyzing cleavage of an enzyme substrate; and a frangible container containing a composition, wherein the composition comprises the enzyme substrate, wherein if the frangible container is broken the composition will contact the bacterial spores to form a mixture having an initial pH in the range from 6.0 to 9.0. The enzyme substrate comprises a fluorinated 4'-alkylumbelliferyl α-D-glucopyranoside represented by the structural formula (I) wherein one of R1 and R2 is F and the other is H, and R3 is an alkyl group having from 1 to 12 carbon atoms. A biological sterilization indicator comprising a kit containing isolated components comprising (i) bacterial spores comprising, and/or capable of producing, an enzyme capable of catalyzing cleavage of the enzyme substrate and a method of assessing efficacy of a sterilization process are also disclosed.
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Page/Page column 56-57
(2020/07/05)
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- a, ? UNSATURATED AMIDE COMPOUND
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The present invention provides an α,β-unsaturated amide compound or a pharmaceutically acceptable salt or the like thereof having anticancer activity and the like represented by the following formula (I): [wherein, "A" represents optionally substituted heterocyclic diyl, R1 represents hydrogen atom or optionally substituted lower alkyl, R2 represents optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aliphatic heterocyclic group or optionally substituted aromatic heterocyclic group, X represents -O-, -S-, -SO2-, -NRX1- (wherein, RX1 represents hydrogen atom or lower alkyl), -CHRX2- (wherein, RX2 represents hydrogen atom or hydroxy), -CH=CH-, -CO- or -NH-CO-, and n1 and n2 are the same or different, and each represents 0 or 1].
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Paragraph 0505
(2018/11/27)
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- Turnover Is rate-limited by deglycosylation for micromonospora viridifaciens sialidase-catalyzed hydrolyses: Conformational implications for the Michaelis complex
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A panel of seven isotopically substituted sialoside natural substrate analogues based on the core structure 7-(5-acetamido-3,5-dideoxy-d-glycero- α-d-galacto-non-2-ulopyranosylonic acid)-(2→6)-β-d- galactopyranosyloxy)-8-fluoro-4-methylcoumarin (1, Neu5Acα2,6GalβFMU) have been synthesized and used to probe the rate-limiting step for turnover by the M. viridifaciens sialidase. The derived kinetic isotope effects (KIEs) on kcat for the ring oxygen (18V), leaving group oxygen (18V), anomeric carbon (13V), C3-carbon (13V), C3-R deuterium (DVR), C3-S deuterium (DV S), and C3-dideuterium (D2V) are 0.986 ± 0.003, 1.003 ± 0.005, 1.021 ± 0.006, 1.001 ± 0.008, 1.029 ± 0.007, 0.891 ± 0.008, and 0.890 ± 0.006, respectively. The solvent deuterium KIE (D2OV) for the sialidase-catalyzed hydrolysis of 1 is 1.585 ± 0.004. In addition, a linear proton inventory was measured for the rate of hydrolysis, under saturating condition, as a function of n, the fraction of deuterium in the solvent. These KIEs are compatible with rate-determining cleavage of the enzymatic tyrosinyl β-sialoside intermediate. Moreover, the secondary deuterium KIEs are consistent with the accumulating Michaelis complex in which the sialosyl ring of the carbohydrate substrate is in a 6S2 skew boat conformation. These KIE measurements are also consistent with the rate-determining deglycosylation reaction occurring via an exploded transition state in which synchronous charge delocalization is occurring onto the ring oxygen atom. Finally, the proton inventory and the magnitude of the solvent KIE are consistent with deglycosylation involving general acid-catalyzed protonation of the departing tyrosine residue rather than general base-assisted attack of the nucleophilic water.
- Chan, Jefferson,Lu, April,Bennet, Andrew J.
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p. 2989 - 2997
(2011/04/25)
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- 3-SUBSTITUTED-1H-INDOLE, 3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
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The invention relates to 3-substituted-1H-indole, 3-substituted-1H-pyrrolo[2,3-b]pyridine, and 3-substituted-1H-pyrrolo[3,2-b]pyridine compounds of the Formula (I): or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
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Page/Page column 92-93
(2010/04/06)
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- 3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
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The invention relates to 3-substituted-1H-pyrrolo[2,3-b]pyridine, and 3-substituted-1H-pyrrolo[3,2-b]pyridine compounds of the Formula 1: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
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Page/Page column 34
(2009/12/23)
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- POTENTIATORS OF GLUTAMATE RECEPTORS
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The present invention provides compounds of formula (I); pharmaceutical compositions thereof, and methods of using the same, processes or preparing the same, and intermediates thereof.
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Page/Page column 114-115
(2010/11/08)
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- Fluorinated xanthene derivatives
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The family of dyes of the invention are fluoresceins and rhodols that are directly substituted on one or more aromatic carbons by fluorine. These fluorine-substituted fluorescent dyes possess greater photostability and have lower sensitivity to pH changes in the physiological range of 6-8 than do non-fluorinated dyes, exhibit less quenching when conjugated to a substance, and possess additional advantages. The dyes of the invention are useful as detectable tracers and for preparing conjugates of organic and inorganic substances.
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- Synthesis, Properties, and Reactivity of N,N'-Difluorobipyridinium and Related Salts and Their Applications as Reactive and Easy-To-Handle Electrophilic Fluorinating Agents with High Effective Fluorine Content
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N,N′-Difluoro-2,2′-, -2,4′-, -3,3′-, -4,4′-bipyridinium and substituted N,N′-difluoro-2,2′-bipyridinmm bis(triflates), bis(tetrafluoroborates), bis(hexafluorophosphates), and bis(hexafluoroantimonates) 1-9 were synthesized in high yields by the direct fluorination of a mixture of a bipyridyl and a Lewis acid, a Br?nsted acid, or the alkali metal salt of an acid. The higher homologues, trimer 10 and polymer 11, were also synthesized. Unsubstituted or electron-donating group-substituted N,N′- difluorobipyridinium salts are stable nonhygroscopic crystals, while the electron-withdrawing group- substituted N,N′-diflurobipyridinium salts 3, 5, and 6 are moisture-sensitive crystals. Hydrolysis of 1b in boiling water gave 3,3′-dihydroxy-2,2′-bipyridyl. The reactivity determination indicated that the fluorinating capability decreased in the order 2,2′- ? 2,4' > 3,3′- ≈ 4,4′-isomer ? N-fluoropyridinium salt and that the two N-F moieties in a molecule were effective for fluorination. This fluorination occurred in a step-by-step manner, and the reactivity difference between the first and second fluorinations was very small. N,N′-Difluoro-2,2′-bipyridinium bis(tetrafluoroborate) (1b) is thus shown to be a highly reactive and easy-to-handle electrophilic fluorinating agent with the high effective fluorine content (103.3 g/kg) for preparing many fluoro organic compounds.
- Umemoto, Teruo,Nagayoshi, Masayuki,Adachi, Kenji,Tomizawa, Ginjiro
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p. 3379 - 3385
(2007/10/03)
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- Synthesis of fluorinated fluoresceins
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Several novel fluorinated fluoresceins (Oregon Green dyes) were prepared by the reaction of fluororesorcinols with phthalic anhydride and its derivatives. A novel regiospecific synthesis of fluororesorcinols was key to the successful synthesis of these new fluorophores. (Polyfluoro)- nitrobenzenes were reacted with 2 equiv of sodium methoxide followed by reduction, hydrodediazoniation, and demethylation, giving the first straightforward synthesis of 2-fluororesorcinol, 4-fluororesorcinol, 2,4- difluororesorcinol, and 2,4,5-trifluororesorcinol. These fluorinated fluoresceins have higher photostability and ionize at a lower pH (pK(a) = 3.3-6.1) than fluorescein (pK(a) = 6.5). Some of the fluorinated fluoresceins have very high quantum yields (0.85-0.97), which, in combination with their lower pK(a)s and high photostability, makes them superior fluorescent dyes for use as reporter molecules in biological systems.
- Sun, Wei-Chuan,Gee, Kyle R.,Klaubert, Dieter H.,Haugland, Richard P.
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p. 6469 - 6475
(2007/10/03)
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