4282-45-5Relevant academic research and scientific papers
Intercepting palladacycles derived by C-H insertion. A mechanism-driven entry to heterocyclic tetraphenylenes
Masselot, David,Charmant, Jonathan P. H.,Gallagher, Timothy
, p. 694 - 695 (2006)
Mechanistic support for the intermediacy of a palladacycle, which has been implicated in the crossover Heck reaction, has been obtained by intercepting this species using biphenylene. This leads to the formation of heterocyclic tetraphenylene derivatives. Three examples of this process are reported, and in two cases, the product structures have been confirmed by X-ray crystallographic analysis. Copyright
BICYCLIC KINASE INHIBITORS AND USES THEREOF
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Paragraph 613; 629, (2021/11/06)
The invention relates to kinase inhibitors, in particular inhibitors of protein kinases including the SIK-family, CSF1R, HCK, TEK-family, BRK, ABL, KIT and/or their mutants. Although structurally similar to other bicyclic kinase inhibitors, the kinase inhibitors of the invention are distinctive; possessing a particular class of heterocyclic moiety. Such kinase inhibitors can display one or more certain properties distinct to their structurally similar kinase inhibitors. The kinase inhibitors of the invention or pharmaceutical compositions comprising them may be used in the treatment of a disorder or condition, such as a proliferative disorder, for example, a leukaemia or solid tumour. In particular, these and other structurally related kinase inhibitors may be used in the treatment of a proliferative disorder - such as a mixed phenotype acute leukaemia (MPAL) - characterised by (inter-alia) the presence of MEF2C protein, a human chromosomal translocation at 11q23, and/or a KMT2A fusion oncoprotein. The kinase inhibitors or pharmaceutical compositions of the invention may be used topically to modulate skin pigmentation in a subject, for example to impart UV protection and reduce skin cancer risk.
Quantifying Through-Space Substituent Effects
Adam, Catherine,Burns, Rebecca J.,Cockroft, Scott L.,Mati, Ioulia K.,Muchowska, Kamila B.
supporting information, p. 16717 - 16724 (2020/07/24)
The description of substituents as electron donating or withdrawing leads to a perceived dominance of through-bond influences. The situation is compounded by the challenge of separating through-bond and through-space contributions. Here, we probe the experimental significance of through-space substituent effects in molecular interactions and reaction kinetics. Conformational equilibrium constants were transposed onto the Hammett substituent constant scale revealing dominant through-space substituent effects that cannot be described in classic terms. For example, NO2 groups positioned over a biaryl bond exhibited similar influences as resonant electron donors. Meanwhile, the electro-enhancing influence of OMe/OH groups could be switched off or inverted by conformational twisting. 267 conformational equilibrium constants measured across eleven solvents were found to be better predictors of reaction kinetics than calculated electrostatic potentials, suggesting utility in other contexts and for benchmarking theoretical solvation models.
Palladium-Catalyzed Electrophilic Functionalization of Pyridine Derivatives through Phosphonium Salts
Che, Yuan-Yuan,Deng, Xuezu,Feng, Chao,Lin, Ling-Zhi,Pei, Bingbing,Yue, Yanni
supporting information, p. 16414 - 16419 (2020/07/20)
Herein, we report a highly efficient and practical method for pyridine-derived heterobiaryl synthesis through palladium-catalyzed electrophilic functionalization of easily available pyridine-derived quaternary phosphonium salts. The nice generality of this reaction was goes beyond arylation, enabling facile incorporation of diverse carbon-based fragments, including alkenyl, alkynyl, and also allyl fragments, onto the pyridine core. Notably, the silver salt additive is revealed to be of vital importance for the success of this transformation and its pivotal role as transmetallation mediator, which guarantees a smooth transfer of pyridyl group to palladium intermediate, is also described.
Photoarylation of Pyridines Using Aryldiazonium Salts and Visible Light: An EDA Approach
Bartolomeu, Aloisio De A.,Brocksom, Timothy J.,De Oliveira, Kleber T.,No?l, Timothy,Silva, Rodrigo C.
, (2019/08/26)
A metal-free methodology for the photoarylation of pyridines, in water, is described giving 2 and 4-arylated-pyridines in yields up to 96percent. The scope of the aryldiazonium salts is presented showing important results depending on the nature and position of the substituent group in the diazonium salt, that is, electron-donating or electron-withdrawing in the ortho, meta, or para positions. Further heteroaromatics were also successfully photoarylated. Mechanistic studies and comparison between our methodology and similar metal-catalyzed procedures are presented, suggesting the occurrence of a visible-light EDA complex which generates the aryl radical with no need for an additional photocatalyst.
RHO-ASSOCIATED PROTEIN KINASE INHIBITOR, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AS WELL AS PREPARATION METHOD AND USE THEREOF
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Paragraph 0136; 0137, (2019/01/11)
The present invention relates to a Rho-associated protein kinase inhibitor of Formula (I), a pharmaceutical composition comprising the same, a preparation method thereof, and use thereof for the prevention or treatment of a disease mediated by the Rho-associated protein kinase (ROCK).
RHO-ASSOCIATED PROTEIN KINASE INHIBITOR, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AS WELL AS PREPARATION METHOD AND USE THEREOF
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Paragraph 0134; 0135, (2019/01/11)
The present invention relates to a Rho-associated protein kinase inhibitor of Formula (I), a pharmaceutical composition comprising the same, a preparation method thereof, and use thereof for the prevention or treatment of a disease mediated by the Rho-associated protein kinase (ROCK).
Synthesis, structure, and synthetic potential of arenediazonium trifluoromethanesulfonates as stable and safe diazonium salts
Filimonov, Victor D.,Krasnokutskaya, Elena A.,Kassanova, Assia Zh.,Fedorova, Valentina A.,Stankevich, Ksenia S.,Naumov, Nikolay G.,Bondarev, Alexander A.,Kataeva, Veronika A.
supporting information, p. 665 - 674 (2018/09/14)
Aromatic diazonium salts are valuable building blocks for organic synthesis; however, in most cases, they are unstable, unsafe, poorly soluble, and/or expensive. In this paper, we have shown that a variety of stable and safe arenediazonium triflates ArN2+ TfO– can be obtained easily and in high yields by diazotization of anilines with tert-butyl nitrite in the presence of trifluoromethanesulfonic acid. Arenediazonium triflates are relatively shelf-stable in the dry state. They dissolve well in water, as well as polar and even nonpolar organic solvents. Less than 800 J/g of energy is released during the thermal decomposition of these salts, which indicates their explosion safety. Arenediazonium triflates have a high reactivity in the known reactions of diazonium chemistry, and undergo an unusual metal-free chlorodediazonization reaction with chloroform and CCl4.
Synthesis of Bi(hetero)aryls via Sequential Oxidation and Decarboxylation of Benzylamines in a Batch/Fully Automated Continuous Flow Process
Mahajan, Bhushan,Aand, Dnyaneshwar,Singh, Ajay K.
supporting information, p. 2831 - 2835 (2018/06/21)
Catalytic dehydrogenative cross-coupling of two C–H bonds represents a green strategy in view of the atom- and step-economy. However, the challenge is to discover a new innovative bond strategy, especially for the direct coupling between Csp2–H
Synthesis and characterization of the first inhibitor of: N -acylphosphatidylethanolamine phospholipase D (NAPE-PLD)
Castellani, Beatrice,Diamanti, Eleonora,Pizzirani, Daniela,Tardia, Piero,Maccesi, Martina,Realini, Natalia,Magotti, Paola,Garau, Gianpiero,Bakkum, Thomas,Rivara, Silvia,Mor, Marco,Piomelli, Daniele
supporting information, p. 12814 - 12817 (2017/12/06)
N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is a membrane-associated zinc enzyme that catalyzes the hydrolysis of N-acylphosphatidylethanolamines (NAPEs) into fatty acid ethanolamides (FAEs). Here, we describe the identification of the first small-molecule NAPE-PLD inhibitor, the quinazoline sulfonamide derivative 2,4-dioxo-N-[4-(4-pyridyl)phenyl]-1H-quinazoline-6-sulfonamide, ARN19874.
