6302-03-0Relevant articles and documents
COMPOUNDS, COMPOSITIONS AND METHODS FOR STABILIZING TRANSTHYRETIN AND INHIBITING TRANSTHYRETIN MISFOLDING
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Paragraph 0808; 0812-0814, (2021/08/06)
Provided herein are compounds having activity against TTR related conditions, and pharmaceutically accepted salts and solvates thereof. Also provided are methods of using the compounds for inhibiting and preventing TTR aggregation and/or amyloid formation in the peripheral nerves, kidney, cardiac tissue, eye and CNS, and of treating a subject with peripheral TTR amyloidosis.
Nickel-Catalyzed Mono-Selective α-Arylation of Acetone with Aryl Chlorides and Phenol Derivatives
Amgoune, Abderrahmane,Derhamine, Sary Abou,Krachko, Tetiana,Monteiro, Nuno,Pilet, Guillaume,Schranck, Johannes,Tlili, Anis
supporting information, p. 18948 - 18953 (2020/09/01)
The challenging nickel-catalyzed mono-α-arylation of acetone with aryl chlorides, pivalates, and carbamates has been achieved for the first time. A nickel/Josiphos-based catalytic system is shown to feature unique catalytic behavior, allowing the highly selective formation of the desired mono-α-arylated acetone. The developed methodology was applied to a variety of (hetero)aryl chlorides including biologically relevant derivatives. The methodology has been extended to the unprecedented coupling of acetone with phenol derivatives. Mechanistic studies allowed the isolation and characterization of key Ni0 and NiII catalytic intermediates. The Josiphos ligand is shown to play a key role in the stabilization of NiII intermediates to allow a Ni0/NiII catalytic pathway. Mechanistic understanding was then leveraged to improve the protocol using an air-stable NiII pre-catalyst.
An Efficient Palladium-Catalyzed α-Arylation of Acetone below its Boiling Point
Ledgard, Andrew J.,Martin, Fionna M.,Mutton, Simon P.,Richardson, Jeffery,Walton, Lesley
, (2020/07/24)
The monoarylation of acetone is a powerful transformation, but is typically performed at temperatures significantly in excess of its boiling point. Conditions described for performing the reaction at ambient temperatures led to significant dehalogenation when applied to a complex aryl halide. We describe our attempts to overcome both issues in the context of our drug-discovery program.
Design of an Indolylphosphine Ligand for Reductive Elimination-Demanding Monoarylation of Acetone Using Aryl Chlorides
Fu, Wai Chung,So, Chau Ming,Chow, Wing Kin,Yuen, On Ying,Kwong, Fuk Yee
supporting information, p. 4612 - 4615 (2015/09/28)
The rational design of a phosphine ligand for the reductive elimination-demanding Pd-catalyzed mono-α-arylation of acetone is demonstrated and reported. The catalyst is tolerant of previously proven challenging electron-deficient aryl chlorides and provides excellent product yields with down to 0.1 mol % Pd. Preliminary investigations suggest that the rate-limiting step for the proposed system is the oxidative addition of aryl chlorides, in which it contradicts previous findings regarding the α-arylation of acetone with aryl halides.
Zheda-phos for general α-monoarylation of acetone with aryl chlorides
Li, Pengbin,Lue, Bo,Fu, Chunling,Ma, Shengming
supporting information, p. 1255 - 1259 (2013/06/27)
A new, readily available, and air-stable monophosphine ligand, i.e., Zheda-Phos, has been developed for the general and highly effective palladium-catalyzed monoarylation of acetone with aryl chlorides. The reaction rate is of first-order dependence with the aryl chloride. Copyright
4-Pyridylanilinothiazoles that selectively target von Hippel - Lindau deficient renal cell carcinoma cells by inducing autophagic cell death
Hay, Michael P.,Turcotte, Sandra,Flanagan, Jack U.,Bonnet, Muriel,Chan, Denise A.,Sutphin, Patrick D.,Nguyen, Phuong,Giaccia, Amato J.,Denny, William A.
supporting information; experimental part, p. 787 - 797 (2010/07/05)
Renal cell carcinomas (RCC) are refractory to standard therapy with advanced RCC having a poor prognosis; consequently treatment of advanced RCC represents an unmet clinical need. The von Hippel-Lindau (VHL) tumor suppressor gene is mutated or inactivated in a majority of RCCs. We recently identified a 4-pyridyl-2-anilinothiazole (PAT) with selective cytotoxicity against VHL-deficient renal cells mediated by induction of autophagy and increased acidification of autolysosomes. We report exploration of structure-activity relationships (SAR) around this PAT lead. Analogues with substituents on each of the three rings, and various linkers between rings, were synthesized and tested in vitro using paired RCC4 cell lines. A contour map describing the relative spatial contributions of different chemical features to potency illustrates a region, adjacent to the pyridyl ring, with potential for further development. Examples probing this domain validated this approach and may provide the opportunity to develop this novel chemotype as a targeted approach to the treatment of RCC. 2009 American Chemical Society.
Studies on antiplatelet agents. I. Synthesis and platelet inhibitory activity of 5-alkyl-2-aryl-4-pyridylimidazoles
Tanaka,Ito,Nishino,Motoyama,Takasugi
, p. 3206 - 3213 (2007/10/02)
5-Alkyl-2-aryl-4-pyridylimidazoles were synthesized and tested in rat ex vivo platelet aggregation studies. Among these compounds, 2-(2-fluorophenyl)-5-methyl-4-(3-pyridyl)imidazole (25) was most potent, and showed 98% inhibition at a dose of 10 mg/kg (p.o.). 25 had inhibitory activity on cyclooxygenase, thromboxane A2 (TXA2) synthetase, and phosphodiesterase, and also showed inhibited KCl-induced contraction of rat aorta. All compounds have little acute toxicity and appear to be free of adverse effects on the stomach.
Nucleophile and Aryl Radical Reactivity in SRN1 Aromatic Nucleophilic Substitution Reactions. Absolute and Relative Electrochemical Determination
Amatore, Christian,Oturan, Mehmet A.,Pinson, Jean,Saveant, Jean-Michel,Thiebault, Andre
, p. 3451 - 3459 (2007/10/02)
Three electrochemical methods are used to obtain the rate of the Ar.+Nu- reaction.In the direct cyclic voltammetric method, the data are derived from the decrease of the substrate peak current upon addition of the nucleophile while in the relative method they are obtained from the peak heights of the two substitution products observed upon repetitive cycling of the substrate solution in the presence of two nucleophiles.In the redox catalysis method , the reduction of the substrate is catalyzed by an exogeneous reversible couple and the data are derived from the decrease of the catalytic current upon addition of the nucleophile.All three methods were combined to determine the reactivities of a series 26 aryl radical-nucleophile couples.In most cases, the rate constant is close to the diffusion limit.The exceptions concern the 2-quinolyl and 2-pyridyl radicals.The results are discussed in terms of energy difference between the ?* and ?* orbitals in the driving force of the reaction as related to characteristic standard potentials and bond energies.
