- A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx
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Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewisx has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewisx and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.
- Conti, Gabriele,Cramer, Jonathan,Ernst, Beat,Girardi, Benedetta,Jiang, Xiaohua,Kokot, Maja,Kroezen, Blijke S.,Luisoni, Enrico,Müller, Jennifer,Rabbani, Said,Ricklin, Daniel,Schwardt, Oliver
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supporting information
p. 1706 - 1719
(2020/09/02)
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- Dehydroxymethylation of alcohols enabled by cerium photocatalysis
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Dehydroxymethylation, the direct conversion of alcohol feedstocks as alkyl synthons containing one less carbon atom, is an unconventional and underexplored strategy to exploit the ubiquity and robustness of alcohol materials. Under mild and redox-neutral reaction conditions, utilizing inexpensive cerium catalyst, the photocatalytic dehydroxymethylation platform has been furnished. Enabled by ligand-to-metal charge transfer catalysis, an alcohol functionality has been reliably transferred into nucleophilic radicals with the loss of one molecule of formaldehyde. Intriguingly, we found that the dehydroxymethylation process can be significantly promoted by the cerium catalyst, and the stabilization effect of the fragmented radicals also plays a significant role. This operationally simple protocol has enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-conjugate additions with Michael acceptors. A broad range of alcohols, from simple ethanol to complex nucleosides and steroids, have been successfully applied to this fragment coupling transformation. Furthermore, the modularity of this catalytic system has been demonstrated in diversified radical-mediated transformations including hydrogenation, amination, alkenylation, and oxidation.
- Zhang, Kaining,Chang, Liang,An, Qing,Wang, Xin,Zuo, Zhiwei
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supporting information
p. 10556 - 10564
(2019/08/20)
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- Dehydroxymethylation of Alcohols Enabled by Cerium Photocatalysis
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Dehydroxymethylation, the direct conversion of alcohol feedstocks as alkyl synthons containing one less carbon atom, is an unconventional and underexplored strategy to exploit the ubiquity and robustness of alcohol materials. Under mild and redox-neutral reaction conditions, utilizing inexpensive cerium catalyst, the photocatalytic dehydroxymethylation platform has been furnished. Enabled by ligand-to-metal charge transfer catalysis, an alcohol functionality has been reliably transferred into nucleophilic radicals with the loss of one molecule of formaldehyde. Intriguingly, we found that the dehydroxymethylation process can be significantly promoted by the cerium catalyst, and the stabilization effect of the fragmented radicals also plays a significant role. This operationally simple protocol has enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-conjugate additions with Michael acceptors. A broad range of alcohols, from simple ethanol to complex nucleosides and steroids, have been successfully applied to this fragment coupling transformation. Furthermore, the modularity of this catalytic system has been demonstrated in diversified radical-mediated transformations including hydrogenation, amination, alkenylation, and oxidation.
- Zhang, Kaining,Chang, Liang,An, Qing,Wang, Xin,Zuo, Zhiwei
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supporting information
p. 10556 - 10564
(2019/08/28)
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- HETEROARYL RHEB INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same. Compositions comprising a compound of this invention or a pharmaceutically acceptable derivative thereof and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The amount of the compound in compositions of this invention is such that it is effective to measurably inhibit Rheb, in a biological sample or in a patient.
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Paragraph 00823
(2018/11/10)
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- Glutaminase inhibitors as well as compositions and applications thereof
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The invention provides a series of heterocyclic compounds expressed in a formula I. The compound comprises glutaminase inhibition activity, and can be used for treating diseases and symptoms related to dysfunction of glutaminase or raising activity of glutaminase.
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Paragraph 0415; 0417; 0432
(2018/01/09)
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- Chemoselective, iron(ii)-catalyzed oxidation of a variety of secondary alcohols over primary alcohols utilizing H2O2 as the oxidant
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A mild, iron-based catalyst system is presented that selectively oxidizes secondary alcohols to the corresponding hydroxy ketones in the presence of primary alcohols within 15 minutes at room temperature, utilizing H 2O2 as the oxidant.
- Lenze, Matthew,Bauer, Eike B.
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supporting information
p. 5889 - 5891
(2013/07/19)
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- 1,3-substitued cycloalkyl derivatives having acidic, mostly heterocyclic groups; processes for their preparation and their use as pharmaceuticals
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The invention relates to 1,3-substituted cycloalkyl derivatives having acidic, mostly heterocyclic groups and to their physiologically acceptable salts and physiologically functional derivatives. What is described are compounds of the formula I, in which the radicals are as defined, and their physiologically acceptable salts and processes for their preparation. The compounds are suitable for the treatment and/or prevention of disorders of fatty acid metabolism and glucose utilization disorders as well as of disorders in which insulin resistence is involved.
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- Regiochemical Control of the Ring-Opening of 1,2-Epoxides by Means of Chelating Processes. 2. Synthesis and Reactions of the cis- and trans-Oxides of 4-cyclohexene, 3-Cyclohexenemethanol, and Methyl 3-Cyclohexenecarboxylate
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The synthesis of the diastereoisomeric epoxides cis-1b-d and trans-2b-d and the products of their ring-opening by various nucleophiles are described.The results of the ring-openings of the trans-epoxides 2b-d can be rationalized by combining stereoelectro
- Chini, Marco,Crotti, Paolo,Flippin, Lee A.,Macchia, Franco,Pineschi, Mauro
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p. 1405 - 1412
(2007/10/02)
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- Enzymatic in vitro Reduction of Ketones. Part 13. Horse Liver Alcohol Dehydrogenase (HLAD) as a Tool for the Synthesis of Enantiomerically Pure Alkyl 3-oxo- and 3-hydroxycyclohexanecarboxylates.
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Enantiomerically pure alkyl 3-oxocyclohexanecarboxylates and the corresponding alcohols have been prepared using HLAD as a suitable catalyst.Kinetic and thermodynamic parameters for the enzymatic reductions are given.The enantiomeric purity and the absolute configuration of the reaction products are determined.The alcohol moiety (methyl, isopropyl or pentyl) of the ester group influences both the steric course and the kinetics of the reduction.Side reactions of the substrate with the reaction medium can be avoided by an appropriate choice of the reaction conditions.
- Willaert, J. J.,Lemiere, G. L.,Dommisse, R. A.,Lepoivre, J. A.,Alderweireldt, F. C.
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p. 2401 - 2423
(2007/10/02)
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