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ANTI-EGFR ANTIBODY DRUG CONJUGATES

The invention relates to anti-Epidermal Growth Factor Receptor (EGFR) antibody drug conjugates (ADCs) which inhibit Bcl-xL, including compositions and methods of using said ADCs.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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An in vitro assay for evaluation of small-molecule inhibitors of cholesterol absorption

Giving cholesterol the brush off: An intestinal brush border membrane vesicle assay has been devised for the convenient in vitro testing of small molecules for inhibition of cholesterol absorption. The assay was used to identify new nonhydrolyzable glycosides as potent cholesterol-absorption inhibitors and an oxazolidinone as an effective replacement of the beta-lactam scaffold of ezetimibe (1).

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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A Novel Method for Stereoselective Glucuronidation

A variety of hydroxylic aglycones can be glucuronidated directly with methyl 2,3,4-tri-O-acetylglucopyranuronate (4a), activated with trimethylsilyl trifluoromethanesulfonate (Me3Si-OTf).This reaction provides mostly beta, and sometimes alpha, glucopyranosiduronic acid derivatives (referred to as glucuronides) rapidly and at low temperatures.The epimeric ratio depends on the relative aglycone nucleophilicity vs. its tendency to form a stabilized carbocation by the formal loss of -OH.Glucuronides of various aromatic and aliphatic aglycones as well as those of a number of cyanohydrins were prepared.The characteristic features of the 1H NMR spectra of alpha and beta derivatives which are presented are useful in the assignment of product stereochemistry and determination of epimeric ratios in those reactions where mixtures are obtained.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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OXAZOLIDINONES AS CHOLESTEROL ABSORPTION INHIBITORS

Novel oxazolidinones and pharmaceutical compositions are described, as are methods of using such compounds and compositions to treat subjects, including humans, suffering from hyperlipidemia, hypercholeserolemia, and atherosclerosis.

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Reference£º
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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METABOLITES OF CERTAIN [1,4]DIAZEPINO[6,7,1-IJ]QUINOLINE DERIVATIVES AND METHODS OF PREPARATION AND USE THEREOF

The invention relates to metabolites of certain [1,4]diazepino[6,7,1-i~]quinoline derivatives and methods of preparation and use thereof. Specifically, the invention relates to compounds of formula I wherein the various substituents are defined herein. The invention also provides pharmaceutical compositions including compounds of formula I, methods of making such compounds, and methods of using such compounds.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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Intermediates for Glucuronide Synthesis: 7-Hydroxycoumarin Glucuronide

A convenient synthesis of the important metabolite 7-hydroxycoumarin glucuronide 3 is presented, including a first report of the beta-imidate 11beta, together with new preparations of the iodosugar 6 and alpha-imidate 11alpha: stability data on 11alpha and 11beta are also given, and the importance of carefully controlled hydrolysis in the last step of the preparation of 3 is emphasised.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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Intermediates for Glucuronide Synthesis: 7-Hydroxycoumarin Glucuronide

A convenient synthesis of the important metabolite 7-hydroxycoumarin glucuronide 3 is presented, including a first report of the beta-imidate 11beta, together with new preparations of the iodosugar 6 and alpha-imidate 11alpha: stability data on 11alpha and 11beta are also given, and the importance of carefully controlled hydrolysis in the last step of the preparation of 3 is emphasised.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Extended knowledge of (2R,3R,4S,5S,6S)-2-Hydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

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Mechanistic insights from substrate preference in unsaturated glucuronyl hydrolase

Natural and synthetic unsaturated glucuronides were tested as substrates for Clostridium perfringens unsaturated glucuronyl hydrolase to probe its mechanism and to guide inhibitor design. Of the natural substrates, a chondroitin disaccharide substrate with sulfation of the primary alcohol on carbon 6 of its N-acetylgalactosamine moiety was found to have the highest turnover number of any substrate reported for an unsaturated glucuronyl hydrolase, with kcat=112 s-1. Synthetic aryl glycoside substrates with electron-withdrawing aglycone substituents were cleaved more slowly than those with electron-donating substituents. Similarly, an unsaturated glucuronyl fluoride was found to be a particularly poor substrate, with k cat/Km=44 nM-1 s-1 – a very unusual result for a glycoside-cleaving enzyme. These results are consistent with a transition state with positive charge at carbon 5 and the endocyclic oxygen, as anticipated in the hydration mechanism proposed. However, several analogues designed to take advantage of strong enzyme binding to such a transition state showed little to no inhibition. This result suggests that further work is required to understand the true nature of the transition state stabilised by this enzyme. Copyright

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Extracurricular laboratory:new discovery of (2R,3R,4S,5S,6S)-2-Hydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

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17alpha- and 17beta-boldenone 17-glucuronides: Synthesis and complete characterization by 1H and 13C NMR

Boldenone is an androgenic anabolic steroid intensively used for growth promoting purposes in animals destined for meat production and as a performance enhancer in athletics. Therefore its use is officially banned either in animals intended for consumption or in humans. Because most anabolic steroids are completely metabolized and usually no parent steroid is excreted, metabolite identification is crucial to detect the illegal use of anabolic steroids either in humans or in livestock. 17alpha- and 17beta-boldenone 17-glucuronides were synthesized, purified and characterized in order to provide suitable standards for the identification and quantification of these metabolites.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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Selective cleavage of sugar anomeric O-acyl groups using FeCl3¡¤6H2O

A convenient method has been developed for regioselective anomeric deacylation of carbohydrate derivatives using FeCl3¡¤6H2O in CH3CN. Operational simplicity, economic consideration, high yield, and low toxicity are key features associated with this protocol.

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Reference£º
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics