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Vascular endothelial growth factor (VEGF) plays important roles in tumor angiogenesis, and the inhibition of its signaling pathway is considered an effective therapeutic option for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of 2-acylamino-6-phenoxy-imidazo[1,2-b]pyridazine derivatives. Hybridization of two distinct imidazo[1,2-b]pyridazines 1 and 2, followed by optimization led to the discovery of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl} oxy)-2-methylphenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide (23a, TAK-593) as a highly potent VEGF receptor 2 kinase inhibitor with an IC50 value of 0.95 nM. The compound 23a strongly suppressed proliferation of VEGF-stimulated human umbilical vein endothelial cells with an IC50 of 0.30 nM. Kinase selectivity profiling revealed that 23a inhibited platelet-derived growth factor receptor kinases as well as VEGF receptor kinases. Oral administration of 23a at 1 mg/kg bid potently inhibited tumor growth in a mouse xenograft model using human lung adenocarcinoma A549 cells (T/C = 8%).

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Chemo-enzymatic cascade processes are invaluable due to their ability to rapidly construct high-value products from available feedstock chemicals. However, they have proven to be challenging because of the mutual inactivation of both catalysts. 40191-32-0, Name is Tetrahydro-2H-pyran-4-carbonyl chloride, molecular formula is C6H9ClO2. In a Article,once mentioned of 40191-32-0, SDS of cas: 40191-32-0

The synthesis of multifunctional spirocycles was achieved from common cyclic carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline, etc.). The whole sequence included only two chemical steps?synthesis of azetidinones, and reduction into azetidines. The obtained spirocyclic amino acids were incorporated into a structure of the known anesthetic drug Bupivacaine. The obtained analogues were more active and less toxic than the original drug. We believe that this discovery will lead to a wide use of spirocyclic building blocks in drug discovery in the near future.

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The present invention provides novel compounds having a P2X3 and/or P2X2/3 receptor antagonistic effect. A pharmaceutical composition having a P2X3 and/or P2X2/3 receptor antagonistic effect comprising a compound of the formula (I): wherein ring A is substituted or unsubstituted 5 to 7-membered cycloalkane, substituted or unsubstituted 5 to 7-membered cycloalkene or the like; C is a carbon atom; ?X? is ?N(R16)? or the like; R16 is hydrogen, substituted or unsubstituted alkyl or the like; R7 is substituted or unsubstituted 5- or 6-membered heteroaryl, substituted or unsubstituted 6 to 10 membered aryl; Q1 and Q2 are each independently a carbon atom or a nitrogen atom; -L- is ?O?, ?S? or the like; R6 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl or the like; R2 is hydrogen, hydroxy or the like, or its pharmaceutically acceptable salt or a solvate thereof.

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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. 40191-32-0, C6H9ClO2. A document type is Article, introducing its new discovery., Electric Literature of 40191-32-0

Herein we report the successful incorporation of a lactam as an amide replacement in the design of hepatitis C virus NS5B Site II thiophene carboxylic acid inhibitors. Optimizing potency in a replicon assay and minimizing potential risk for CYP3A4 induction led to the discovery of inhibitor 22a. This lead compound has a favorable pharmacokinetic profile in rats and dogs.

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Novel quinoline compounds of formula (I), pharmaceutical compositions containing such compounds and their use in therapy, as bromodomain inhibitors

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A series of novel 3-amidophenols with 5-heteroatomic substitutions were designed and synthesized. Several compounds showed potent antitubercular activity against Mycobacterium tuberculosis H37Ra (MIC = 0.25?5 mug/mL). Compounds 12j and 14i also displayed good inhibitory activity against M. tuberculosis H37Rv and two clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.39?3.12 mug/mL). The privileged compound 14i showed certain oral efficacy on a mouse infection model. The compounds are non-cytotoxic against L-O2 hepatocytes and RAW264.7 macrophagocytes. They did not exert inhibitory activity against representative Gram-positive and Gram-negative bacteria.

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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. 40191-32-0, Name is Tetrahydro-2H-pyran-4-carbonyl chloride, molecular formula is C6H9ClO2. In a Article,once mentioned of 40191-32-0, Safety of Tetrahydro-2H-pyran-4-carbonyl chloride

The intramolecular 1,5-H transfer reaction of the aryl radicals generated from unactivated aryl iodides by photocatalysis is described. The features of this transformation are operational simplicity, excellent yields, mild reaction conditions, and good functional group tolerance. With this approach, a more concise formal synthesis of (±)-coerulescine and (±)-physovenine is accomplished.

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The IAPs are key regulators of the apoptotic pathways and are commonly overexpressed in many cancer cells. IAPs contain one to three BIR domains that are crucial for their inhibitory function. The pro-survival properties of XIAP come from binding of the BIR domains to the pro-apoptotic caspases. The BIR3 domain of XIAP binds and inhibits caspase 9, while the BIR2 domain binds and inhibits the terminal caspases 3 and 7. While XIAP BIR3 inhibitors have previously been reported, they also inhibit cIAP1/2 and promote the release of TNFalpha, potentially limiting their therapeutic utility. This paper will focus on the optimization of selective XIAP BIR2 inhibitors leading to the discovery of highly potent benzodiazepinone 36 (IC50 = 45 nM), which has high levels of selectivity over XIAP BIR3 and cIAP1 BIR2/3 and shows efficacy in a xenograft pharmacodynamic model monitoring caspase activity while not promoting the release of TNFalpha in vitro.

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In this study, we describe the synthesis and structure-activity relationship (SAR) of a series of isoquinoline chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists. TASP0376377 (15-20), one of the most potent compounds, showed a potent binding affinity (IC50 = 19 nM) in addition to the excellent functional antagonist activity (IC50 = 13 nM). Moreover, the efficacy of this compound in a chemotaxis assay (IC50 = 23 nM) was in good agreement with its potency as a CRTH2 antagonist. In addition, 15-20 exhibited greater selectivity in binding to CRTH2 than to the DP1 prostanoid receptor (IC 50 >1 muM) or the enzymes COX-1 and COX-2 (IC50 >10 muM).

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Compounds of formulae I and II: [image] are disclosed as 5-HT3 inhibitors. Those compounds are useful in treating CINV, IBS-D and other diseases and conditions.

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