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Fused tricyclic compounds as inhibitors of 17beta-hydroxysteroid dehydrogenase 3

Fused tricyclic compounds, methods of using such compounds in the treatment of hormone sensitive diseases such as prostate cancer, and pharmaceutical compositions containing such compounds.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands

Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Ligand-free Suzuki coupling reaction with highly recyclable ionic palladium catalyst, Ti1-xPdxO2-x (x?=?0.03)

We synthesized a recyclable palladium ionic catalyst, Ti0.97Pd0.03O1.97, using a solution combustion method (SCM), and characterized by XRD and Rietveld refinement. The synthesized Pd ionic catalyst is stable, insensitive to moisture and air, and easy to handle. The new catalyst has exhibited a phenomenal result for the Suzuki-Miyaura cross-coupling reaction with a broad substrate scope, and the reaction proceeds in an aqueous medium. The new catalyst proved beneficial and produced excellent yields irrespective of aryl halide used in the reaction (electron-rich or electron-poor or heterocyclic compounds) and shown a turnover frequency (TOF) of 14?25 h?1 for different reactions. The catalyst was coated on a cordierite monolith (Mg2Al4Si5O18), which enhanced the applicability of the catalyst, and made the handling and recycling of the catalyst very easy. Suzuki Miyaura reaction was carried out using both Pd-powder catalysts as well as the Pd-coated honeycomb, which gave almost similar results. We have demonstrated the recyclability of Pd coated cordierite monolith and shown the superiority of the catalyst over the other Pd catalysts for the Suzuki-Miyaura reaction.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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ALKYL-AMIDE-SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFNalpha RESPONSES

Compounds having the following formula (I): or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNalpha, by acting on Tyk-2 to cause signal transduction inhibition.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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A Pd(II)-catalyzed ring-expansion reaction of cyclic 2-azidoalcohol derivatives: Synthesis of azaheterocycles

(Chemical Equation Presented) A Pd(II)-catalyzed ring expansion-reaction of cyclic 2-azidoalcohol derivatives was found to proceed via an unprecedented C-C bond cleavage-C-N bond formation sequence, providing substituted azaheterocycles.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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A pharmaceutical intermediate nitro-substituted sulfonyl synthetic method of compound (by machine translation)

The invention relates to a can be useful as pharmaceutical intermediates of the formula shown in (III) of the nitro-substituted sulfonyl synthetic method of compound, said method comprising: in the organic solvent, in catalyst, nitryl source compound, the presence of alkali and oxidation promoter, variety under (I) in the compound represented by the formula (II) compounds and 70? 90 C react under, the reaction time is 4? 7 hours, after post-processing, thereby obtaining said formula (III) compound, wherein R 1, R 2 each independently selected from H, C 1? C 6 alkyl, C 1? C 6 alkoxy or halogen; X is halogen. The stated method, through the suitable reaction substrate, catalyst, nitryl source compound, alkali, organic solvent and oxidation promoting the comprehensive selection and synergistic, thus can yield to obtain the target product, has good on industry application prospect and production potential. (by machine translation)

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Scalable total synthesis and biological evaluation of haouamine A and its atropisomer

(Chemical Equation Presented) A total synthesis of the complex, bent aromatic ring-containing marine alkaloid haouamine A is achieved through a route in which every step (with the exception of the final deprotection) is performed on a gram-scale. This is accomplished through the development of a method for the dehydrogenation of cyclohexenones that allows for point-to-planar chirality transfer. This strategy makes it possible to program the desired atropisomeric outcome from a simple chiral cyclohexenone. By synthesizing atrop-haouamine A, this work has firmly established that natural haouamine exists as a single, nonequilibrating atropisomer. Finally, biological investigations demonstrate that the bent aromatic ring of this natural product is critical for anticancer activity against PC3 cells.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Synthesis of Benzoacridines and Benzophenanthridines by Regioselective Pd-Catalyzed Cross-Coupling Reactions Followed by Acid-Mediated Cycloisomerizations

A convenient synthesis of various benzoacridines and benzophenanthridines from readily available dihalogenated quinolines is reported. The synthesis is based on regioselective Suzuki and Sonogashira reactions followed by Br¡ãnsted acid-mediated cycloisomerization. The developed methodology is highly modular and allows the construction of various ring systems and substitution patterns in high yields. The optical and electrochemical properties of selected derivatives were investigated.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The Multiple Facets of Iodine(III) Compounds in an Unprecedented Catalytic Auto-amination for Chiral Amine Synthesis

Iodine(III) reagents are used in catalytic one-pot reactions, first as both oxidants and substrates, then as cross-coupling partners, to afford chiral polyfunctionalized amines. The strategy relies on an initial catalytic auto C(sp3)?H amination of the iodine(III) oxidant, which delivers an amine-derived iodine(I) product that is subsequently used in palladium-catalyzed cross-couplings to afford a variety of useful building blocks with high yields and excellent stereoselectivities. This study demonstrates the concept of self-amination of the hypervalent iodine reagents, which increases the value of the aryl moiety.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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4-ALKYL SUBSTITUTED 3,4-DIHYDROPYRROLO[1,2-a]PYRAZIN-1(2H)-ONE DERIVATIVES AS KINASES INHIBITORS

The present invention relates to 4-alkyl substituted 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one derivatives which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them.

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method