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SUBSTITUTED TRIAZINE DERIVATIVES AND USE THEREOF AS STIMULATORS OF SOLUBLE GUANYLATE CYCLASE

The present application relates to novel substituted fused pyrimidines, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.

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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 new heterobimetallic palladium-[60]fullerene complex with bidentate bis-1,1?-[P]2-ferrocene ligand

A new heterobimetallic palladium-[60]fullerene complex with ferrocene bis-phosphine ligand was prepared using alternative paths: either via addition reaction of Pd2(dba)3¡¤C6H6 (dba=dibenzylidenacetone) in the presence of 1,1?-bis(diphenylphosphino)ferrocene (dppf) to C60, or via electrochemical activation of C60 to generate C602- anions, which then react with PdCl2 and dppf to yield the target complex. The obtained (eta2-C60)Pd(dppf) complex was characterized by 1H- and 31P-{1H}-NMR and electronic spectroscopy as well as electrochemically.

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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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Identification of potent tricyclic prodrug S1P1 receptor modulators

Recently, our research group reported the identification of prodrug amino-alcohol 2 as a potent and efficacious S1P1 receptor modulator. This molecule is differentiated preclinically over the marketed drug fingolimod (Gilenya 1), whose active phosphate metabolite is an S1P1 full agonist, in terms of pulmonary and cardiovascular safety. S1P1 partial agonist 2, however, has a long half-life in rodents and was projected to have a long half-life in humans. The purpose of this communication is to disclose highly potent partial agonists of S1P1 with shorter half-lives relative to the clinical compound 2. PK/PD relationships as well as their preclinical pulmonary and cardiovascular safety assessment are discussed.

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

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Photoinduced electron transfer in ruthenium(II) trisbipyridine complexes connected to a naphthalenebisimide via an oligo(phenyleneethynylene) spacer

The preparation and the characterization of three new dyads composed of a ruthenium trisbipyridine complex linked to a naphthalene bisimide electron acceptor via a phenyleneethynylene spacer of different length (one or two units) are reported. The dyads also differ by the anchoring position of the spacer on the bipyridine, which is appended either at the 4-position or the 5-position. Cyclic voltammetry and the UV-Vis absorption spectroscopy suggested that the spacer linked at the 5-position ensures a longer pi-conjugation length but the electron transfer rates indicate a lower electronic coupling, than in 4-position. Photoinduced emission yields indicate a significant quenching of the MLCT excited-state of the ruthenium complex in these dyads. Except for the dyad linked in 5 position with one phenyleneethynylene unit, the transient absorption spectroscopy of all the other dyads evidences that the MLCT excited-state decays almost exclusively by electron transfer to form the charge-separated state RuIII-NBI-. This state could not be observed, presumably because the subsequent recombination to the ground state was much faster than its formation. In the dyad linked in 5 position with only one phenyleneethynylene unit, at room temperature, the 3MLCT* state is in equilibrium with the 3NBI* state, and it also decays via electron transfer. The notable feature of these dyads is first the occurrence of a relatively long-range electron transfer reaction via a bis(phenylethynylene) linking unit anchored at the 5 position. Secondly, we show within these series of compounds that subtle variations in the structure of the dyads (length of the spacer and anchoring position on bipy) have a strong impact on the rates and in the mechanism of decay of the 3MLCT* state. The photophysical properties of the dyads can be explained in terms of energy proximity of different excited states and magnitude of the electronic coupling according to the anchoring position. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

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

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QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORgammat activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

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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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New staves for old barrels: Regioisomeric (12,2 2,33,42,53,62,7 3,82)-p-octiphenyl rods with an NMR tag

The usefulness of rigid-rod p-octiphenyls with the novel 1 2,22,33,42,53,6 2,73,82-motif as staves in rigid-rod beta-barrel pores is evaluated. Comparison with the known characteristics of isomeric pores with the common 13,23,32,4 3,52,63,72,83-sequence indicates that the self-assembly and the supramolecular chirality of rigid-rod beta-barrels are independent of the substitution pattern of the p-octiphenyl stave. NMR tags added at the rod termini are shown to facilitate product characterization. the Royal Society of Chemistry the Centre National de la Recherche Scientifique 2006.

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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 New Alkynyl-Bridged 2,5-Disubstituted 1,3,4-Oxadiazoles

A synthesis of new alkynyl-derived 2,5-disubstituted 1,3,4-oxadiazoles through palladium/copper-catalyzed Sonogashira cross-coupling between oxadiazole-substituted phenyl bromides and various arylacetylenes is described. Investigation of the absorption and emission spectra of the target compounds indicates emission profiles in the near-blue and blue region and high luminescence intensities. The presented approach is very convenient for the synthesis of luminescent small-molecules or precursors of other complex derivatives that are useful in the preparation of OLEDs as electron-transporting components.

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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 a new class of 1,4-bis(diphenylphosphino)-1,3-butadiene bridged diphosphine, NUPHOS, via zirconium-mediated reductive coupling of alkynes and diynes: Applications in palladium-catalyzed cross-coupling reactions

The synthesis of a new class of 1,4-bis(diphenylphosphino)-1,3-butadiene was discussed. Catalyst mixtures based on 1,2,3,4-Ph4-NUPHOS were found to be superior to those based on BINAP, with activities of 6900 and 260 (mol of product) (mol of palladium)-1h-1 respectively. The applications in palladium catalyzed cross-coupling reactions were also discussed.

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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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BIARYL AMIDE COMPOUNDS AS KINASE INHIBITORS

The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.

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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 targetable fluorescent probe for imaging hydrogen peroxide in the mitochondria of living cells

We present the design, synthesis, and biological applications of mitochondria peroxy yellow 1 (MitoPY1), a new type of bifunctional fluorescent probe for imaging hydrogen peroxide levels within the mitochondria of living cells. MitoPY1 combines a chemoselective boronate-based switch and a mitochondrial-targeting phosphonium moiety for detection of hydrogen peroxide localized to cellular mitochondria. Confocal microscopy and flow cytometry experiments in a variety of mammalian cell types show that MitoPY1 can visualize localized changes in mitochondrial hydrogen peroxide concentrations generated by situations of oxidative stress. Copyright

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