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Hydrolase enzymes and their use in kinetic resolution

The invention relates to hydrolases and to polynucleotides encoding the hydrolases. In addition, the invention relates to the use of these hydrolase enzymes in kinetic resolution.

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Tetrahydrofuran – Wikipedia,
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Discovery and SAR study of piperidine-based derivatives as novel influenza virus inhibitors

A series of piperidine-based derivatives were identified as novel and potent inhibitors of the influenza virus through structural modification of a compound that was selected from a high-throughput screen. Various analogues were synthesized and confirmed as inhibitors. The structure-activity relationship (SAR) studies suggested that the ether linkage between the quinoline and piperidine is critical for the inhibitory activity. The optimized compound tert-butyl 4-(quinolin-4-yloxy)piperidine-1-carboxylate 11e had an excellent inhibitory activity against influenza virus infection from a variety of influenza virus strains, with EC50values as low as 0.05 muM. The selectivity index value (SI = MLD50/EC50) of 11e is over 160 000 based on cytotoxicity, measured by MTT assays of three cell lines. We carried out a time-of-addition experiment to delineate the mechanism of inhibition. The result indicates that 11e interferes with the early to middle stage of influenza virus replication.

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IDO1 INHIBITOR AND PREPARATION METHOD AND APPLICATION THEREOF

A compound as an indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, and an application thereof in the field of IDO1-related diseases, and in particular a compound as shown in formula (I) and a pharmaceutically acceptable salts thereof.

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Tetrahydrofuran – Wikipedia,
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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 453-20-3, name is 3-Hydroxytetrahydrofuran, introducing its new discovery. Quality Control of 3-Hydroxytetrahydrofuran

PRODRUGS OF TREPROSTINIL

Prodrugs of treprostinil are provided which can be used in the treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

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Archives for Chemistry Experiments of 3-Hydroxytetrahydrofuran

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B(C6F5)3-Catalyzed Silation of Alcohols: A Mild, General Method for Synthesis of Silyl Ethers

The commercially available borane tris(pentafluorophenyl)borane, B(C6F5)3, is an effective catalyst for the dehydrogenative silation of alcohols using a variety of silanes, R3SiH, R2SiH2, and R2R?SiH. Generally, the reactions occur in a convenient time frame at room temperature using 2 mol % of the borane and are clean and high yielding, with dihydrogen as the only byproduct. Primary aliphatic alcohols are silated cleanly but slowly, with reaction times ranging from 20 to 144 h. Faster reaction times can be achieved by increasing the catalyst loading to 8 mol % or by heating the reaction to ?60C. Secondary and tertiary alcohols react more rapidly, with most reactions being complete in 0.5-2 h. The reaction is tolerant of many functional groups including C=C, C=C, -Br, aliphatic ketones, C(O)OR, lactones, furans, OBn, OMe, and NO2; examples of each are given. Using the phenolic substrate 2,4,6-trimethylphenol, a number of different silanes were tested. Only the most bulky silanes (Bn3SiH and Pri3SiH) were not reactive under these conditions. The selectivity of the silation reactions are roughly governed by the relative basicity of the alcohols (and other functions in the molecule) with more basic groups being selectively silated. These observations are rationalized on the basis of a mechanism that invokes borane activation of the silane by hydride abstraction. The resulting intermediate silylium/hydridoborate ion pair then reacts with alcohols to give the observed silyl ether and dihydrogen products.

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Tetrahydrofuran – Wikipedia,
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Vapor-phase reaction of polyols over copper catalysts

The vapor-phase reaction of triols and diols was performed over copper metal catalysts. Triols, such as 1,2,3-propanetriol (glycerol) and 1,2,3- and 1,2,4-butanetriols, were dehydrated to afford corresponding hydroxyketones, while 1,2-propanediol was dehydrogenated to form hydroxyacetone. Supported copper as well as pure copper metal was an effective catalyst for the dehydration of glycerol to produce hydroxyacetone under inert conditions. In hydrogen flow, however, copper catalyzed the hydrogenation of hydroxyacetone as well as hydrogenolysis to produce ethylene glycol. Alumina-supported copper showed the highest catalytic activity with hydroxyacetone selectivity of >90 mol% at ambient pressure of nitrogen and 250 C. Copper metal provides an active site for the dehydration of glycerol. We propose a reaction mechanism for the dehydration of glycerol to form hydroxyacetone.

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Tetrahydrofuran – Wikipedia,
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Green synthesis of dimethyl isosorbide

A green synthetic approach for dimethyl isosorbide (DMI) with dimethylcarbonate (DMC) in the presence of a base is reported. The easy methylation of isosorbide may be due to its unique structure (which enhances the nucleophilicity of the hydroxyl groups), and to the effect of the hydrogen bonding which increases the reactivity of the molecule towards DMC.

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Synthesis and SAR of 2-aryloxy-4-alkoxy-pyridines as potent orally active corticotropin-releasing factor 1 receptor antagonists

A series of 2-aryloxy-4-alkoxy-pyridines (1) was identified as novel, selective, and orally active antagonists of the corticotropin-releasing factor 1 (CRF1) receptor. Among these, compound 2 (CP-316311) is a potent and selective CRF1 receptor antagonist with an IC50 value of 6.8 nM in receptor binding and demonstrates oral efficacy in central nervous system (CNS) in vivo models. The regiochemistry of compounds in this series was determined by an X-ray structural analysis. A method to control regioselectivity via pyridine-N-oxides was developed. The synthesis of compounds in series 1 (Figure 1) and [3H]-2 as well as the structure-activity relationship (SAR) are discussed. The in vitro, ex vivo, and in vivo properties of representative compounds are described herein. Compound 2 was advanced to phase II depression trials to test the hypothesis that CRF1 antagonists could be used clinically as antidepressant drugs.

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Tetrahydrofuran – Wikipedia,
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Domino Two-Step Oxidation of beta-Alkoxy Alcohols to Hemiacetal Esters: Linking a Stoichiometric Step to an Organocatalytic Step with a Common Organic Oxidant

Primary and secondary beta-alkoxy alcohols can be cleanly and efficiently oxidized into hemiacetal esters in a cascade two-step process. mCPBA serves both as a stoichiometric oxidant in the first TEMPO-catalyzed step, converting alcohols to aldehydes/ketones, and as a reagent in the second Baeyer?Villiger stoichiometric oxidation, transforming the aldehydes/ketones into hemiacetal esters. The use of an oxidant common to both steps enables the domino reaction to proceed under a single experimental setting. Longer oxidative cascade sequences are possible when this new methodology is applied to suitable substrates.

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Tetrahydrofuran – Wikipedia,
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Coumarin derivatives protect against ischemic brain injury in rats

Neuroprotection strategies are of great importance in the treatment of ischemic brain injury. Screening of our in-stock coumarin derivatives identified compound 1 as exhibiting neuroprotective activity. Subsequently, a structural optimization was carried out, which led to the discovery of the potent compound 20. This compound signi ficantly attenuated the damage in a cell line derived from a pheochromocytoma of the rat adrenal medulla induced by oxygen-glucose deprivation in vitro. Furthermore, compound 20 exhibited clear neuroprotection in middle cerebral artery occlusion rats by reducing infarct size and brain-water content, improving neurological function, and suppressing neuronal loss and neuropathological changes in the cortex and hippocampus. Pharmacokinetic evaluation indicated that compound 20 could penetrate the blood-brain barrier of rats.

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Tetrahydrofuran – Wikipedia,
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