155020-44-3Relevant articles and documents
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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Page/Page column 55, (2021/04/02)
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.
Dual Inhibition of Mnk2 and FLT3 for potential treatment of acute myeloid leukaemia
Diab, Sarah,Abdelaziz, Ahmad M.,Li, Peng,Teo, Theodosia,Basnet, Sunita K.C.,Noll, Ben,Rahaman, Muhammed H.,Lu, Jingfeng,Hou, Jinqiang,Yu, Mingfeng,Le, Bich T.,Albrecht, Hugo,Milne, Robert W.,Wang, Shudong
supporting information, p. 762 - 772 (2017/09/02)
The discovery of novel anti-AML therapeutic agents is urgently needed, but the complex heterogeneity of the disease has so far hampered the development of a curative treatment. FLT3 inhibitors have shown therapeutic potential in clinical trials; but a monotherapy regimen has been associated with resistance mediated by the activation of parallel signalling circuitry, including MAPK and mTOR. Therefore, inhibiting a nexus of the two signalling pathways along with inhibition of FLT3 might be advantageous. Herein, we propose that a dual inhibition of FLT3 and Mnk would provide a better clinical option for AML patients compared to targeting FLT3 alone. Thus, a series of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amines and 4-(indol-3-yl)-N-phenylpyrimidin-2-amines were prepared. Potent Mnk2 inhibitors, FLT3 inhibitors, and dual inhibitors of Mnk2 and FLT3 were identified and their anti-proliferative activities assessed against MV4-11 AML cell lines. Dual inhibition of FLT3 and Mnk2 caused the increased apoptotic cell death of MV4-11 cells compared to inhibition of FLT3 or Mnk2 alone.
1 -HYDROXY-BENZOOXABOROLES AS ANTIPARASITIC AGENTS
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Page/Page column 85, (2014/10/03)
Provided are compounds useful for controlling endoparasites both in animals and agriculture. Further provided are methods for controlling endoparasite infestations of an animal by administering an effective amount of a compound as described above, or a pharmaceutically acceptable salt thereof, to an animal, as well as formulations for controlling endoparasite infestations using the compounds described above or an acceptable salt thereof, and an acceptable carrier. The claimed compounds are described by the following Markush formula:A typical example for a compound according to above formula is: A typical example for a compound according to above formula is:
Turnover Is rate-limited by deglycosylation for micromonospora viridifaciens sialidase-catalyzed hydrolyses: Conformational implications for the Michaelis complex
Chan, Jefferson,Lu, April,Bennet, Andrew J.
supporting information; experimental part, p. 2989 - 2997 (2011/04/25)
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.
NOVEL TUBULIN POLYMERISATION INHIBITORS
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Page/Page column 90, (2008/06/13)
The present invention relates to compounds of general formula (I) as tublin polymerisation inhibitors and methods for preparing such compounds.
Fluorinated xanthene derivatives
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, (2008/06/13)
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.
Synthesis of fluorinated fluoresceins
Sun, Wei-Chuan,Gee, Kyle R.,Klaubert, Dieter H.,Haugland, Richard P.
, p. 6469 - 6475 (2007/10/03)
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.
The Effect of Fluorine Substitution on the Metabolism and Antimalarial Activity of Amodiaquine
O'Neill, Paul M.,Harrison, Anthony C.,Storr, Richard C.,Hawley, Shaun R.,Ward, Stephen A.,Park, B. Kevin
, p. 1362 - 1370 (2007/10/02)
Amodiaquine (AQ) (2) is a 4-aminoquinoline antimalarial which causes adverse side effects such as agranulocytosis and liver damage.The observed drug toxicity is believed to be related to the formation of an electrophilic metabolite, amodiaquine imine (AQQI), which can bind to cellular macro-molecules and initiate hypersensitivity reactions. 5'-Fluoroamodiaquine (5'-FAQ, 3), 5',6'-difluoroamodiaquine (5',6'-DIFAQ, 4), 2',6'-difluoroamodiaquine (2',6'-DIFAQ, 5), 2',5',6'-trifluoroamodiaquine (2',5',6'-TRIFAQ, 6) and 4'-dehydroxy-4'-fluoroamodiaquine (4'-deOH-4'-FAQ, 7) have been synthesized to assess the effect of fluorine substitution on the oxidation potential, metabolism, and in vitro antimalarial activity of amodiaquine.The oxidation potentials were measured by cyclic voltammetry, and it was observed that substitution at the 2',6'- and 4'-positions (2',6'-DIFAQ and 4'-deOH'4'-FAQ) produced analogues with significantly higher oxidation potentials than the parent drug.Fluorine substitution at the 2',6'-positions and 4'-position also produced analogues that were more resistant to bioactivation.Thus 2',6'-DIFAQ and 4'-deOH-4'-FAQ produced thioether conjugates corresponding to 2.17percent (SD: +/-0.27percent) and 0percent of the dose compared with 11.87percent (SD: +/-1.31percent) of the dose for amodiaquine.In general the fluorinated analogues had similar in vitro antimalarial activity to amodiaquine against the chloroquine resistant K1 strain of Plasmodium falciparum and the chloroquine sensitive T9-96 strain of P. falciparum with the notable exception of 2',5',6'-TRIFAQ (6).The data presented indicate that fluorine substitution at the 2',6'-positions and replacement of the 4'-hydroxyl of amodiaquine with fluorine produces analogues ( 5 and 7) that maintain antimalarial efficacy in vitro and are more resistant to oxidation and hence less likely to form toxic quinone imine metabolites.
