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INHIBITORS OF LYSINE GINGIPAIN

The present invention relates generally to therapeutics targeting the bacterium Porphyromonas gingivalis, including its protease Lysine gingipain (Kgp), and their use for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer’s disease. In certain embodiments, the invention provides compounds according to Formula I, as described herein, and pharmaceutically acceptable salts thereof.

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

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Kinetic and structural insights into the binding of histone deacetylase 1 and 2 (HDAC1, 2) inhibitors

The structure?activity and structure?kinetic relationships of a series of novel and selective ortho-aminoanilide inhibitors of histone deacetylases (HDACs) 1 and 2 are described. Different kinetic and thermodynamic selectivity profiles were obtained by varying the moiety occupying an 11?A channel leading to the Zn2+catalytic pocket of HDACs 1 and 2, two paralogs with a high degree of structural similarity. The design of these novel inhibitors was informed by two ligand-bound crystal structures of truncated hHDAC2. BRD4884 and BRD7232 possess kinetic selectivity for HDAC1 versus HDAC2. We demonstrate that the binding kinetics of HDAC inhibitors can be tuned for individual isoforms in order to modulate target residence time while retaining functional activity and increased histone H4K12 and H3K9 acetylation in primary mouse neuronal cell culture assays. These chromatin modifiers, with tuned binding kinetic profiles, can be used to define the relation between target engagement requirements and the pharmacodynamic response of HDACs in different disease applications.

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

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A new procedure for highly stereoselective and regioselective synthesis of 2-ethynyl-3-hydroxytetrahydropyran derivatives based on alkyne-Co2(CO)6 complex

Treatment of trans-epoxides 3 with Co2(CO)8 gave the corresponding cobalt complexes, which were subsequently exposed to a catalytic amount of BF3¡¤OEt2 at -78C to provide exclusively cis-2-ethynyl-3- hydroxytetrahydropyran derivatives via endo mode cyclization pathway. cis- Congeners, cis-3 afforded the corresponding trans tetrahydropyran derivatives exclusively. This novel cyclization has been found to proceed with retention of configuration at the propynyl stereogenic center. Requirement for stereoselectivity in cyclization was discussed.

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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

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COMBINATION TREATMENTS COMPRISING IMIDAZOPYRAZINONES FOR THE TREATMENT OF PSYCHIATRIC AND/OR COGNITIVE DISORDERS

The present invention provides combination treatments comprising administration of compounds that are PDE1 enzyme inhibitors and other compounds useful in the treatment of psychiatric and/or cognitive disorders such as for example Attention Deficit Hyperactivity Disorder (ADHD), depression, anxiety, narcolepsy, schizophrenia, cognitive impairment or cognitive impairment associated with schizophrenia (CIAS). Separate aspects of the invention are directed to the combined use of said compounds for the treatment of psychiatric and/or cognitive disorders. The present invention also provides pharmaceutical compositions comprising said PDE1 enzyme inhibitors together with other compounds useful in the treatment of psychiatric and/or cognitive disorders.

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

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Decarboxylative alkynylation and cyanation of carboxylic acids using photoredox catalysis and hypervalent iodine reagents

Alkynes and nitriles are important functional groups that serve as versatile building blocks in organic synthesis and find applications in material and medicinal sciences. A convenient and straightforward access to both classes of compounds under mild conditions is, therefore, highly desirable. Herein, we disclose the decarb-oxylative alkynylation and cyanation of broadly available carboxylic acids using photoredox catalysis and hyper-valent iodine reagents. Choices of both catalysts and reagents were crucial. Computational and experimental studies revealed two different possible mechanisms that are dictated by the oxidation potential of the reagents: radical for alkynylation, ionic for cyanation.

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

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Aminomethylene oxindoles

This invention provides aminomethylene oxindole compounds represented by the formula STR1 wherein R is H or loweralkyl; R’ is loweralkyl, aralkyl, or R and R’ taken together form a chain of the formula wherein X is CH2 or NR” where R” is loweralkyl, loweralkanoyl, aroyl, alkoxycarbonyl or aryl; and the pharmaceutically acceptable acid addition salts thereof. The compounds of this invention are useful as antihypertensive agents.

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

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Direct photochemical cross-coupling between aliphatic acids and BF3K salts

We describe a novel photoredox hetero-coupling reaction of two C (sp3) radicals from aliphatic acids or BF3K salts. The kinetic differences in radical persistence provide cross-selectivity, using an organic photoredox catalyst and an oxidant with visible light. This method exhibits broad scope, including several examples constructing sterically hindered C(sp3)-C(sp3) bonds.

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

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The reactant in an enzyme-catalyzed reaction is called a substrate. Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction.I hope my blog about 51673-83-7 is helpful to your research., Application In Synthesis of Tetrahydro-2H-pyran-2-carboxylic acid

The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.51673-83-7, Name is Tetrahydro-2H-pyran-2-carboxylic acid, molecular formula is C6H10O3. In a Patent£¬once mentioned of 51673-83-7, Application In Synthesis of Tetrahydro-2H-pyran-2-carboxylic acid

Substituted Pyrrolidines and Methods of Use

The invention discloses compounds of Formula (I) wherein R1, R2, R2A, R3, R3A, R4, R4A, and R5 are as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

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

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Lithium enolates in the enantioselective construction of tetrasubstituted carbon centers with chiral lithium amides as noncovalent stereodirecting auxiliaries

Lithium enolates derived from carboxylic acids arc 0 0 OH ubiquitous intermediates in organic synthesis. Asymmetric transformations with these intermediates, a central goal of organic synthesis, are typically carried out with covalently attached chiral 0 auxiliaries. An alternative approach is to utilize chiral reagents that form discrete form discrete, well-defined aggregates with lithium enolates, H’ 0 R3 0 providing a chiral environment conducive of asymmetric bond 986 ee formation. These reagents effectively act as noncovalent, or R’ = OMe. Me good yields RI traceless, chiral auxiliaries. Lithium amides are an obvious choice Michael addition for such reagents as they are known to form mixed aggregates with lithium enolates. We demonstrate here that mixed aggregates can chiral directing reagent readily recovered in >95% yield effect highly enantioselective transformations of lithium enolates in several classes of reactions, most notably in transformations forming tetrasubstituted and quaternary carbon centers. Easy recovery of the chiral reagent by aqueous extraction is another practical advantage of this one-step protocol. Crystallographic, spectroscopic, and computational studies of the central reactive aggregate, which provide insight into the origins of selectivity, are also reported.

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

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N-Tetrahydrofuroyl-(L)-phenylalanine derivatives as potent VLA-4 antagonists.

Given the proposed involvement of VLA-4 in inflammatory processes, a program to identify orally active VLA-4 antagonists was initiated. Herein, we report the discovery of a N-tetrahydrofuroyl-(L)-phenylalanine derivative (17) and related analogues as potent VLA-4 antagonists with good oral bioavailability.

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