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The invention relates to substituted dihydroquinazolines and to a method for the production thereof, the use thereof for treating and/or preventing diseases and for producing drugs for treating and/or preventing diseases, in particular for the use of the inventive dihydroquinazolines in the form of antiviral agents, in particular against cytomegaloviruses.

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Piperidine – Wikipedia,
Piperidine | C5H7980N – PubChem

 

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Compounds of Formula (00A) and methods of use as Janus kinase inhibitors are described herein.

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Piperidine – Wikipedia,
Piperidine | C5H8112N – PubChem

 

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We report on a series of electron donor?acceptor conjugates incorporating a ZnII?porphyrin-based electron donor and a variety of non-conjugated rigid linkers connecting to push?pull chromophores as electron acceptors. The electron acceptors comprize multicyanobutadienes or extended tetracyanoquinodimethane analogues with first reduction potentials ranging from ?1.67 to ?0.23 V vs. Fc+/Fc in CH2Cl2, which are accessible through a final-step cycloaddition?retroelectrocyclization (CA-RE) reaction. Characterization of the conjugates includes electrochemistry, spectroelectrochemistry, DFT calculations, and photophysical measurements in a range of solvents. The collected data allows for the construction of multiple Marcus curves that consider electron-acceptor strength, linker length, and solvent, with data points extending well into the inverted region. The enhancement of electron?vibration couplings, resulting from the rigid spacers and, in particular, multicyano-groups in the conformationally highly fixed push?pull acceptor chromophores affects the charge-recombination kinetics in the inverted region drastically.

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Piperidine – Wikipedia,
Piperidine | C5H7877N – PubChem

 

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Currently, synergistic inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) and histone deacetylases (HDACs) has been a potential effective strategy for cancer treatment. Herein, by combining critical pharmacophores in approved drugs olaparib and chidamide, a series of novel 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid derivatives were designed and synthesized. All efforts led to a good dual PARP-1/HDAC-1 inhibitor, compound 4, with IC50 values of 4.2 and 340 nM against PARP-1 and HDAC-1, which were as potent as olaparib and chidamide respectively. The MTT assay further demonstrated that compound 4 had potent inhibitory activities against BRCA1/2-proficient K562 and MDA-MB-231 cells with GI50 values of 5.6 and 4.3 muM, respectively. Therefore, our results suggested that compound 4 could be a promising dual PARP-1/HDAC-1 inhibitor for further studies. In addition, a few excellent PARP-1 inhibitors such as 7?9 and HDAC-1 inhibitors such as 12 were serendipitously discovered, which also could be further studied in our next work.

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Piperidine – Wikipedia,
Piperidine | C5H8094N – PubChem

 

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A novel series of compounds obtained by fusing the acetylcholinesterase (AChE) inhibitor donepezil and the antioxidant melatonin were designed as multi-target-directed ligands for the treatment of Alzheimer’s disease (AD). In vitro assay indicated that most of the target compounds exhibited a significant ability to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (eqBuChE and hBuChE), and beta-amyloid (Abeta) aggregation, and to act as potential antioxidants and biometal chelators. Especially, 4u displayed a good inhibition of AChE (IC50value of 193 nM for eeAChE and 273 nM for hAChE), strong inhibition of BuChE (IC50value of 73 nM for eqBuChE and 56 nM for hBuChE), moderate inhibition of Abeta aggregation (56.3% at 20 muM) and good antioxidant activity (3.28 trolox equivalent by ORAC assay). Molecular modeling studies in combination with kinetic analysis revealed that 4u was a mixed-type inhibitor, binding simultaneously to catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 4u could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood?brain barrier (BBB). Taken together, these results strongly indicated the hybridization approach is an efficient strategy to identify novel scaffolds with desired bioactivities, and further optimization of 4u may be helpful to develop more potent lead compound for AD treatment.

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Piperidine – Wikipedia,
Piperidine | C5H8157N – PubChem

 

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The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML), may require alpha-isoform specific targeting. The scorpion shaped GSK-3 inhibitors developed by our group achieved the highest GSK-3alpha selectivity reported so far but suffered from insufficient aqueous solubility. This work presents the solubility-driven optimization of our isoform-selective inhibitors using a scorpion shaped lead. Among 15 novel compounds, compound 27 showed high activity against GSK-3alpha/beta with the highest GSK-3alpha selectivity reported to date. Compound 27 was profiled for bioavailability and toxicity in a zebrafish embryo phenotype assay. Selective GSK-3alpha targeting in AML cell lines was achieved with compound 27, resulting in a strong differentiation phenotype and colony formation impairment, confirming the potential of GSK-3alpha inhibition in AML therapy.

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C-N cross-coupling is an important class of reactions with far-reaching impacts across chemistry, materials science, biology, and medicine. Transition metal complexes can elegantly orchestrate diverse aminations but typically require demanding reaction conditions, precious metal catalysts, or oxygen-sensitive procedures. Here, we introduce a mild nickel-catalyzed C-N cross-coupling methodology that operates at room temperature using an inexpensive nickel source (NiBr2·3H2O), is oxygen tolerant, and proceeds through direct irradiation of the nickel-amine complex. This operationally robust process was employed for the synthesis of diverse C-N-coupled products (40 examples) by irradiating a solution containing an amine, an aryl halide, and a catalytic amount of NiBr2·3H2O with a commercially available 365 nm LED at room temperature without added photoredox catalyst and the amine substrate serving additional roles as the ligands and base. Density functional theory calculations and kinetic isotope effect experiments were performed to elucidate the observed C-N cross-coupling reactivity.

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The present invention relates to new class of functionalized macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.5

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To develop PET tracers for imaging of neuroinflammation, new carbon-11-labeled sEH/PDE4 dual inhibitors have been synthesized. The reference standard N-(4-methoxy-2-(trifluoromethyl)benzyl)benzamide (1) and its corresponding desmethylated precursor N-(4-hydroxy-2-(trifluoromethyl)benzyl)benzamide (2) were synthesized from (4-methoxy-2-(trifluoromethyl)phenyl)methanamine and benzoic acid in one and two steps with 84% and 49% overall chemical yield, respectively. The standard N-(4-methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (MPPA, 4) and its precursor N-(4-hydroxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (5) were synthesized from methyl 4-piperidinecarboxylate, propionyl chloride and (4-methoxy-2-(trifluoromethyl)phenyl)methanamine in two and three steps with 62% and 34% overall chemical yield, respectively. The target tracers N-(4-[11C]methoxy-2-(trifluoromethyl)benzyl)benzamide ([11C]1) and N-(4-[11C]methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide ([11C]MPPA, [11C]4) were prepared from their corresponding precursors 2 and 5 with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 25?35% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (AM) at EOB was 370?740 GBq/mumol with a total synthesis time of 35?40-minutes from EOB.

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The present invention provides DNA-nanostructures comprising and at least one targeting moiety, wherein the at least one targeting moiety is linked to the DNA-nanostructure; and wherein the at least one targeting moiety is nicotine or a nicotine analogue. These compounds elicit an immunogenic response in individuals and are useful as vaccines for ameliorating nicotine dependence.

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