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Cannabinoid receptor 1 (CB1) antagonists are potentially useful for the treatment of several diseases. However, clinical development of several CB1 antagonists was halted due to central nervous system (CNS)-related side effects including depression and suicidal ideation in some users. Recently, studies have indicated that selective regulation of CB1 receptors in the periphery is a viable strategy for treating several important disorders. Past efforts to develop peripherally selective antagonists of CB1 have largely targeted rimonabant, an inverse agonist of CB1. Reported here are our efforts toward developing a peripherally selective CB1 antagonist based on the otenabant scaffold. Even though otenabant penetrates the CNS, it is unique among CB1 antagonists that have been clinically tested because it has properties that are normally associated with peripherally selective compounds. Our efforts have resulted in an orally absorbed compound that is a potent and selective CB1 antagonist with limited penetration into the CNS.

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The present disclosure relates to a domain to bromine BET through a combination of compounds to inhibit protein function, and its use in therapy. (by machine translation)

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Platelet-derived growth factor receptor beta (PDGFRbeta) is a transmembrane tyrosine kinase receptor and it is upregulated in various malignant tumors. Radiolabeled PDGFRbeta inhibitors can be a convenient tool for the imaging of tumors overexpressing PDGFRbeta. In this study, [125I]-1-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinoline-8-yl}piperidin-4-amine ([125I]IIQP) and [125I]-N-3-iodobenzoyl-1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}-piperidin-4-amine ([125I]IB-IQP) were designed and synthesized, and their potential as PDGFRbeta imaging agents was evaluated. In cellular uptake experiments, [125I]IIQP and [125I]IB-IQP showed higher uptake by PDGFRbeta-positive cells than by PDGFRbeta-negative cells, and the uptake in PDGFRbeta-positive cells was inhibited by co-culture with PDGFRbeta ligands. The biodistribution of both radiotracers in normal mice exhibited hepatobiliary excretion as the main route. In mice inoculated with BxPC3-luc (PDGFRbeta-positive), the tumor uptake of radioactivity at 1 h after the injection of [125I]IIQP was significantly higher than that after the injection of [125I]IB-IQP. These results indicated that [125I]IIQP can be a suitable PDGFRbeta imaging agent. However, further modification of its structure will be required to obtain a more appropriate PDGFRbeta-targeted imaging agent with a higher signal/noise ratio.

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Two-photon excitation (TPE) probe-based fluorescence imaging has become one of the most attractive diagnostic techniques to investigate biomolecules and biological events in live cells and tissues. At the current stage most of the TPE-based sensing is reflected by fluorescence intensity changes. Nevertheless the mere altering of intensity could be facilely affected by ambient conditions. On the other hand, TPE probes based on an intramolecular charge transfer (ICT) strategy could solve this problem to some extent with a morphology change-induced emission shift. However their applications are yet constrained due to the inherent limitation of ICT, e.g. the high degree of overlap of two emissions bands and shifts of the TPE maxima. To achieve the desired TPE-based sensing and to circumvent the problems stated above, we adapted a Foerster resonance energy transfer (FRET) strategy to develop small molecule ratiometric TPE fluorescent probes. Our FRET-based ratiometric TPE fluorescent probe displays a remarkable emission shift (up to 125 nm) with two well-resolved emission bands. Hence the ratio of these two emission bands could enable the measurement of fluorescence changes more accurately, thus further improving imaging in live cells and deep tissues. To the best of our knowledge, the current reported probe has the largest emission shift among all the small molecule ratiometric TPE fluorescent probes while the maximum TPE wavelength remains unchanged. This work has provided a FRET approach to fabricate novel small molecule ratiometric TPE fluorescent probes that improve imaging in deep tissues. This journal is

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Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 73874-95-0, molcular formula is C10H20N2O2, introducing its new discovery. Application In Synthesis of tert-Butyl piperidin-4-ylcarbamate

Leukotriene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and inflammatory conditions.

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A new series of 12-benzyl matrinic amide/ethanamide derivatives were synthesized from matrinine (1) and evaluated for their anti-HCV activity, taking compound 2 as the lead. SAR revealed that the introduction of a suitable substituent at the N?-end of matrinic amide might greatly enhance the potency. Among them, matrinic acid 17 and N?-substituted matrinic amides 18a?d exhibited promising potency with low micromolar EC50values ranging from 1.03 mumol/L to 7.54 mumol/L, and better therapeutic window with SI from 66 to 132. Moreover, compound 17 displayed an excellent PK and safety profile in vivo, demonstrating good drug-like characteristics. Thus, it has been selected for further investigation, with an advantage of decreased chances of inducing drug-resistance mutations.

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Compounds of the following formula are provided for use with kinases: (I) Wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds

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The invention provides compounds of general formula (I) wherein m, n, Q, Z1, Z2, R1, R2, R3, R4, R5, R6, R7 and R8 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

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A 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented by the generalformula (1): [Chemical formula 1] (1) or a pharmaceutically acceptable saltthereof. They are useful as a therapeutic/preventive agent for diabetes, diabeticnephropathy, or glomerulosclerosis.

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Compounds of formula (I) wherein A, R, W, Q, L, n and m have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer’s disease.

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