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The recently discovered enzyme tyrosyl-DNA phosphodiesterase 2 (TDP2) has been implicated in the topoisomerase-mediated repair of DNA damage. In the clinical setting, it has been hypothesized that TDP2 may mediate drug resistance to topoisomerase II (topo II) inhibition by etoposide. Therefore, selective pharmacological inhibition of TDP2 is proposed as a novel approach to overcome intrinsic or acquired resistance to topo II-targeted drug therapy. Following a high-throughput screening (HTS) campaign, toxoflavins and deazaflavins were identified as the first reported sub-micromolar and selective inhibitors of this enzyme. Toxoflavin derivatives appeared to exhibit a clear structure-activity relationship (SAR) for TDP2 enzymatic inhibition. However, we observed a key redox liability of this series, and this, alongside early in vitro drug metabolism and pharmacokinetics (DMPK) issues, precluded further exploration. The deazaflavins were developed from a singleton HTS hit. This series showed distinct SAR and did not display redox activity; however low cell permeability proved to be a challenge.

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Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction by binding to a specific portion of an enzyme. Irreversible inhibitors are therefore the equivalent of poisons in heterogeneous catalysis. 50675-18-8, C6H10O2. A document type is Patent, introducing its new discovery., HPLC of Formula: C6H10O2

The invention discloses a compound containing an aromatic ring, its preparation method, pharmaceutical composition and application. The invention provides a formula 1 shown including aromatic ring of the compound, its pharmaceutically acceptable salt, a stereoisomer thereof, a tautomer thereof or a solvate thereof, this compound can be effectively combines the BRD4 BET family, BRD3, BRD2 and BRDT of bromine structure territory, in order to adjust the downstream gene c – myc and its […] gene transcription, thereby regulating downstream of the signal path, with specific roles, including the treatment of diseases such as inflammatory diseases, cancer and AIDS; wherein a portion of the compound has high activity, and have better cellular activity and metabolic stability, so that it may be effective drug for the treatment of tumor. (by machine translation)

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Tetrahydropyran – Wikipedia,
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Chemistry can be defined as the study of matter and the changes it undergoes. You’ll sometimes hear it called the central science because it is the connection between physics and all the other sciences, starting with biology. 50675-18-8, Name is Tetrahydropyran-4-carbaldehyde, molecular formula is C6H10O2. In a Patent，once mentioned of 50675-18-8, name: Tetrahydropyran-4-carbaldehyde

In one aspect, the present invention provides compounds having formula (1) or (100), a salt thereof or a hydrate of the foregoing, which compounds exhibit excellent cell adhesion inhibitory action or cell infiltration inhibitory action, and are useful as therapeutic or prophylactic agents for various inflammatory diseases and autoimmune diseases associated with adhesion and infiltration of leukocytes, such as inflammatory bowel disease (particularly ulcerative colitis or Crohn”s disease), irritable bowel syndrome; rheumatoid arthritis, psoriasis, multiple sclerosis, asthma and atopic dermatitis. [image] wherein R10 represents optionally substituted cycloalkyl, etc., R20-23 represent hydrogen, alkyl, alkoxy, etc., R30-32 represent hydrogen, alkyl, oxo, etc., and R40 represents optionally substituted alkyl, etc.

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A new series of linear and angular alkyl substituted furochromanone derivatives have been synthesized in one pot microwave irradiation assisted process from ortho-hydroxy acetyl (linear and angular) benzofurans and aliphatic aldehydes in the presence of pyrrolidine. Various alkyl substituted furochromanones were synthesized with high yields. The in vitro antimicrobial activity of the products was tested. The structures of the compound have been elucidated on the basis of elemental analysis, IR, 1H and 13C NMR, and MS spectral data.

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A series of 5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H- imidazole derivatives was synthesized as transforming growth factor-beta (TGF-beta) type I receptor (also known as activin-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and for their TGF-beta-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. As a representative compound, 16i was a potent and selective ALK5 inhibitor, exhibiting a good enzyme inhibitory activity (IC50 = 5.5 nM) as well as inhibitory activity against TGF-beta-induced Smad2/3 phosphorylation at a cellular level (IC50 = 36 nM). Furthermore, the topical application of 3% 16i lotion significantly inhibited Smad2 phosphorylation in Mouse skin (90% inhibition compared with vehicle-treated animals).

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Tetrahydropyran – Wikipedia,
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A novel two-step synthesis of multisubstituted beta-prolinols has been developed, featuring a [3+2] cycloaddition of azomethine ylides and a programmed reduction triggered by the combination of borane and lithium aluminum hydride (LAH). beta-Prolinols are shown to be valuable building blocks for polyheterocycles.

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Chemistry involves the study of all things chemical – chemical processes, chemical compositions and chemical manipulation – in order to better understand the way in which materials are structured, how they change and how they react in certain situations.50675-18-8, Name is Tetrahydropyran-4-carbaldehyde, molecular formula is C6H10O2. In a Article，once mentioned of 50675-18-8, Application In Synthesis of Tetrahydropyran-4-carbaldehyde

7-Arylsulfonyl substituted benzofuropiperidine was discovered as a novel scaffold for 5HT6 receptor antagonists. Optimization by substitution at C-1 position led to identification of selective, orally bioavailable, brain penetrant antagonists with reduced hERG liability. An advanced analog tested in rat social recognition model showed significant activity suggesting potential utility in the enhancement of short-term memory.

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Compounds are disclosed that have formula I: where A, B, L 1 , W, Y, R 1 , and R 3 are as defined herein. The compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non- limiting example, pain, anxiety, depression, inflammation, cognitive disorders, weight and eating disorders, Parkinson’s disease, Alzheimer’s disease, spasticity, addiction, glaucoma, and others

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Disclosed are (cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles and their use as CB2 cannabinoid receptor agonists, pharmaceutical compositions containing the same, and their use for the treatment of CB2 receptor mediated disorders or conditions.

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4-Cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate (3b) is a potent, selective and systemically active inhibitor of intracellular NAAA activity, which produces profound anti-inflammatory effects in animal models. In the present work, we describe structure-activity relationship (SAR) studies on 3-aminoazetidin-2-one derivatives, which have led to the identification of 3b, and expand these studies to elucidate the principal structural and stereochemical features needed to achieve effective NAAA inhibition. Investigations on the influence of the substitution at the beta-position of the 2-oxo-3-azetidinyl ring as well as on the effect of size and shape of the carbamic acid ester side chain led to the discovery of 3ak, a novel inhibitor of human NAAA that shows an improved physicochemical and drug-like profile relative to 3b. This favourable profile, along with the structural diversity of the carbamic acid chain of 3b, identify this compound as a promising new tool to investigate the potential of NAAA inhibitors as therapeutic agents for the treatment of pain and inflammation.

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Tetrahydropyran – Wikipedia,
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