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Novel treatments for bipolar disorder with improved efficacy and broader spectrum of activity are urgently needed. Glycogen synthase kinase 3beta (GSK-3beta) has been suggested to be a key player in the pathophysiology of bipolar disorder. A series of novel GSK-3beta inhibitors having the common N-[(1-alkylpiperidin-4-yl)methyl]-1H-indazole-3-carboxamide scaffold were prepared taking advantage of an X-ray cocrystal structure of compound 5 with GSK-3beta. We probed different substitutions at the indazole 5-position and at the piperidine-nitrogen to obtain potent ATP-competitive GSK-3beta inhibitors with good cell activity. Among the compounds assessed in the in vivo PK experiments, 14i showed, after i.p. dosing, encouraging plasma PK profile and brain exposure, as well as efficacy in a mouse model of mania. Compound 14i was selected for further in vitro/in vivo pharmacological evaluation, in order to elucidate the use of ATP-competitive GSK-3beta inhibitors as new tools in the development of new treatments for mood disorders.

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

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Note that a catalyst decreases the activation energy for both the forward and the reverse reactions and hence accelerates both the forward and the reverse reactions.Recommanded Product: [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), you can also check out more blogs about72287-26-4

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The palladium catalysed Miyaura cross-coupling reactions of 4?-(4-bromophenyl)-2,2?:6?,2?-terpyridine (tpy-phi-Br) and 4?-bromo-2,2?:6?,2?-terpyridine (tpy-Br) with bis(neopentyl glycolato)diboron (B2neo2 lead to the first reported examples of boronate ester-substituted terpyridine ligands, L1 and L2. Ligand L1, which incorporates a benzene ring between the terpyridine group and the boron, reacts with transition metals such as iron and ruthenium to generate complexes containing the analogous boronic acid-substituted terpyridine L3. The heteroleptic complex [Ru(ttpy)L3]2+ has also been prepared by an analogous cross-coupling reaction of the bromo complex [Ru(ttpy)(tpy-phi-Br)]2+ with B2neo2 (ttpy =4?-tolyl-2,2?:6?,2?-terpyridine). The structurally related complex [Ru(ttpy)L4]2+ (L4 = terpyridine-4?-boronic acid) could not be prepared, either directly from L2 or from [Ru(ttpy)(tpy-Br)]2+, apparently due to competitive hydrodeboration and solvolysis. The complex [Ru(ttpy)L3]2+ reacts with aryl halides under standard palladium-catalysed Suzuki-Miyaura cross-coupling conditions to generate more elaborate 4?-aryl-substituted terpyridyl complexes. Cross-coupling has also been achieved by reaction of [Ru(ttpy)(tpy-Br)]2+ with an arylboronic acid. The photophysical properties of [Ru(ttpy)L3]2+ are shown to be largely typical of ruthenium bis-terpyridyl complexes.

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

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3-(Hetero)aryl substituted indoles, 7-azaindoles, and pyrroles can be obtained in a very concise fashion via a one-pot Masuda borylation-Suzuki coupling sequence. The concise total syntheses of the marine natural products meridianins A (5) and G (4i) nicely illustrate the utility of this methodology.

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

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The present invention relates to pyrazine derivatives of formula I, and pharmaceutical compositions including the same, that are inhibitors of one or more FGFR enzymes and are useful in the treatment of FGFR-associated diseases such as cancer. Wherein ring A is selected from

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

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Supramolecular chiral induction has been observed in five dinuclear triple-stranded helicates composed entirely of achiral components. Three different chiral cations were found to be very effective at inducing high levels of enantiomeric enrichment in racemic mixtures of the helicates. The mechanism of intermolecular chiral induction in one cation-helicate pair, s-nic/K 6[Ga2L13], has been elucidated through circular dichroism spectroscopy, X-ray crystallography, and one and two-dimensional NMR spectroscopy (s-nic = N-methyl-s-nicotinium, H 4L1 = 1,4-bis(2?,3?-dihydroxybenzamido) phenylene).

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

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The application of borylated N-aryl sulfoximines as newly designed synthetic building blocks in Suzuki-type cross coupling reactions offers rapid access to a wide range of N-biaryl derivatives with potential relevance for medicinal chemistry and crop protection in good to excellent yields (up to 98%). (Figure presented.).

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

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The invention concerns a compound represented by formula (1) below, and an organic EL device using the same. The compound of the invention is useful as an electron transport material that contributes to improvement in service life prolongation, reduction of driving voltage, achievement of high efficiency and so forth, above all, improvement in achieving high efficiency, and can provide an excellent organic EL device: wherein, Ar is an m-valent group derived from aromatic hydrocarbon or an aromatic heterocycle; X1 to X6 are ?CR1? or ?N?, at least two of X1 to X6 is ?CR1?, R1 in two of ?CR1? is a bonding hand to be bonded with Ar or an azole ring, and R1 in ?CR1? other than the above is hydrogen or alkyl having 1 to 4 carbons; Y is ?O? or ?S?; at least one of hydrogen in an azole ring may be replaced by alkyl, phenyl or naphthyl; m is an integer from 2 to 4; and at least one of hydrogen in each ring and alkyl in the formula may be replaced by deuterium.

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

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In search of prospective agents against infectious diseases, 1,1?-bis(diphenylphosphino)ferrocene pyridine-2-thiolato-1-oxide M(II) hexafluorophosphate compounds [M(mpo)(dppf)](PF6), where M = palladium or platinum, were synthesized and fully characterized in the solid state and in solution using experimental and DFT computational techniques. The compounds are isomorphous and the M(II) transition metal ions are in a nearly planar trapezoidal cis-coordination bound to the pyridine-2-thiolato-1-oxide (mpo) and to the 1,1?-bis(diphenylphosphino)ferrocene molecules, both acting as bidentate ligands. Both compounds showed high cytotoxic activity on Trypanosoma cruzi and Mycobacterium tuberculosis (MTB) and acceptable selectivities towards MTB, but good to excellent selectivity index values as anti-T. cruzi compounds. The inclusion of the ferrocene moiety (dppf ligand) improved the selectivity towards the parasite when compared to the previously reported [M(mpo)2] complexes. Related to the probable mechanism of action of the complexes, molecular docking studies on modelled T. cruzi NADH-fumarate reductase (TcFR) predicted that both be very good inhibitors of the enzyme. The effect of the compounds on the enzyme activity was experimentally confirmed using T. cruzi protein extracts. According to all obtained results, both [M(mpo)(dppf)](PF6) compounds could be considered prospective anti-trypanosomal agents that deserve further research.

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

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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 69861-71-8, name is Bis(tri-o-tolylphosphine)palladium(0), introducing its new discovery. Product Details of 69861-71-8

This paper presents effects of varying bidentate phosphine steric properties, electronic properties, and bite angle on product ratios in the amination of aryl bromides. Comparison of the ratios of amine products to dehydrohalogenation products showed that catalysts containing electron rich, modestly hindered phosphines with small bite angles (~-90) gave the best selectivities. Surprisingly, the arene side product formed from reaction of alkylamines deuterated in the N-H position or deuterated in the position alpha to the nitrogen showed low levels of deuterium incorporation in many examples. Steric properties and ligand bite angle had the greatest impact on the selectivity for monoarylation versus diarylation of primary amines; ligands with small bite angles gave higher monoarylation-to-diarylation ratios, as did ligands with increased steric bulk. Electron poor or sterically hindered bidentate phosphines reduced the amount of product resulting from aryl exchange of electron rich palladium-bound arenes with those of aryl groups on the phosphine ligands.

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

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Application of 69861-71-8, Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Article, and a compound is mentioned, 69861-71-8, Bis(tri-o-tolylphosphine)palladium(0), introducing its new discovery.

Palladium thiolato complexes [(L)Pd(R)(SR’)], within which L is a chelating ligand such as DPPE, DPPP, DPPBz, DPPF, or TRANSPHOS, R is a methyl, alkenyl, aryl, or alkynyl ligand, and R’ is an aryl or alkyl group, were synthesized by substitution or proton-transfer reactions. All of these thiolato complexes were found to undergo carbon-sulfur bond-forming inductive elimination in high yields to form dialkyl sulfides, diaryl sulfides, alkyl aryl sulfides, alkyl alkenyl sulfides, and alkyl alkynyl sulfides. Reductive eliminations forming alkenyl alkyl sulfides and aryl alkyl sulfides were the fastest. Eliminations of alkynyl alkyl sulfides were slower, and elimination of dialkyl sulfide was the slowest. Thus the relative rates for sulfide elimination as a function of the hybridization of the palladium-bound carbon follow the trend sp2 > sp >> sp3. Rates of reductive elimination were faster for cis-chelating phosphine ligands with larger bite angles. Kinetic studies, along with results from radical trapping reactions, analysis of solvent effects; and analysis of complexes with chelating phosphines of varying rigidity, were conducted with [Pd(L)(S-tert-butyl)(Ar)] and [Pd(L)(S- tert-butyl)(Me)]. Carbon-sulfur bond-forming reductive eliminations involving both saturated and unsaturated hydrocarbyl groups proceed by an intramolecular, concerted mechanism. Systematic changes in the electronic properties of the thiolate and aryl groups showed that reductive elimination is the fastest for electron deficient aryl groups and electron rich arenethiolates, suggesting that the reaction follows a mechanism in which the thiolate acts as a nucleophile and the aryl group an electrophile. Studies with thiolate ligands and hydrocarbyl ligands of varying steric demands favor a migration mechanism involving coordination of the hydrocarbyl ligand in the transition state.

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