- Design, synthesis and evaluation of an NLRP3 inhibitor diazirine photoaffinity probe
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The NLRP3 inhibitor MCC950/CRID3 ameliorates a remarkable number of inflammatory disorders in animal models. Herein we describe a trifluoromethyl phenyl diazirine (TPD) photoaffinity probe, called TPD-950-Br, to probe the molecular interactions of MCC950. We show that TPD-950-Br covalently captures proximal species upon photo-activation and inhibits IL-1β production in an NLRP3 inhibitor assay.
- Coll, Rebecca C.,Hill, James R.,Robertson, Avril A. B.,Schroder, Kate
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supporting information
(2020/04/02)
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- Bianthryl-based organocatalysts for the asymmetric Henry reaction of fluoroketones
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We have developed a catalytic system based on bianthrylbis(thiourea) for the asymmetric Henry reaction of fluoroketones and nitroalkanes that resulted from the screening of a library containing 31 chiral non-racemic organocatalysts. The corresponding adducts were isolated in up to 6 times shorter reaction time in comparison with the previously published organocatalysts. High levels of stereocontrol have been generally observed, with measured product enantiomeric excesses up to 97% and diastereomeric ratio 3:2 (anti/syn). The above-mentioned catalysts have been successfully applied to the total asymmetric synthesis of CF3-tethered (S)-halostachines, which has proved that this method constitutes an easy entry to similar enantiopure compounds.
- Otevrel, Jan,Svestka, David,Bobal, Pavel
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supporting information
p. 5244 - 5248
(2019/06/07)
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- Oxidation of α-trifluoromethyl and non-fluorinated alcohols: Via the merger of oxoammonium cations and photoredox catalysis
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We present an alcohol oxidation strategy to access α-trifluoromethyl ketones (TFMKs) merging catalytic oxoammonium cation oxidation with visible-light photoredox catalysis. This work uses 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl as an organic oxidant capable of generating TFMKs in good yields. The methodology serves as an improvement over previous reports of an analogous oxidation strategy requiring superstoichiometric quantities of oxidant. Both primary and secondary non-fluorinated alcohols can also be oxidised in good yields.
- Pistritto, Vincent A.,Paolillo, Joshua M.,Bisset, Kathryn A.,Leadbeater, Nicholas E.
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supporting information
p. 4715 - 4719
(2018/07/06)
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- SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME
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ABSTRACT The present invention provides for certain sulfonyl ureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome. Such compounds are useful in the treatment of a wide range of disorders in which the inflammation process, or more specifically the NLRP3 inflammasome, have been implicated as being a key factor.
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Page/Page column 155
(2016/09/15)
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- THIENO[3,2-D]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases.
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Paragraph 0624; 0625; 0626
(2015/01/06)
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- Highly efficient synthesis of aryl and heteroaryl trifluoromethyl ketones via o-iodobenzoic acid (IBX)
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A two-step process for the synthesis of aryl and heteroaryl trifluoromethyl ketones from the corresponding aldehydes is described. Trifluoromethyl alcohols were prepared from aryl and heteroaryl aldehydes in excellent yields using catalytic amount of K2CO3. The trifluoromethyl alcohols were then oxidized conveniently and efficiently by o-iodoxybenzoic acid (IBX) under mild conditions to get the desired functionalized aryl and heteroaryl trifluoromethyl ketones.
- Cheng, Huicheng,Pei, Yu,Leng, Faqiang,Li, Jingya,Liang, Apeng,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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p. 4483 - 4486
(2013/07/26)
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- THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases
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Page/Page column 89; 90
(2013/07/19)
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- Oxidation of α-trifluoromethyl alcohols using a recyclable oxoammonium salt
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A simple, mild method for the oxidation of α-trifluoromethyl alcohols to trifluoromethyl ketones (TFMKs) using the oxoammonium salt 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) is described. Under basic conditions, oxidation proceeds rapidly and affords good to excellent yields of TFMKs, without concomitant formation of the hydrate. The byproduct of the oxidation, 4-acetylamino-2,2,6,6-tetramethyl-1- piperidinyloxy (1c), is easily recovered and can be conveniently reoxidized to regenerate the oxoammonium salt.
- Kelly, Christopher B.,Mercadante, Michael A.,Hamlin, Trevor A.,Fletcher, Madison H.,Leadbeater, Nicholas E.
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p. 8131 - 8141
(2013/01/15)
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- A Weinreb amide approach to the synthesis of trifluoromethylketones
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A novel route to access trifluoromethylketones (TFMKs) from Weinreb amides is reported. This represents the first documented case of the Ruppert-Prakash reagent (TMS-CF3) reacting in a constructive manner with an amide and enables synthesis of TMFKs without risk of over-trifluoromethylation.
- Rudzinski, Diandra M.,Kelly, Christopher B.,Leadbeater, Nicholas E.
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supporting information
p. 9610 - 9612
(2012/10/29)
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- SUBSTITUTED 3-PHENYLPROPIONIC ACIDS AND THE USE THEREOF
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The present application relates to novel 3-phenylpropionic acid derivatives, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular disorders.
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Page/Page column 64
(2011/06/23)
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- SULFUR-CONTAINING HETEROCYCLIC DERIVATIVE HAVING ?-SECRETASE-INHIBITING ACTIVITY
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The following compound is provided as an agent for treating a disease induced by production, secretion and/or deposition of amyloid β protein, for example,. a compound represented by the formula (I): wherein ruing A is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group, R1 is optionally substituted lower alkyl or the like, R2a and R2b are each independently hydrogen, optionally substituted lower alkyl or the like, R3a and R3c are each independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl or the like, or a pharmaceutically acceptable salt thereof, or a solvate thereof.
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Page/Page column 63-64
(2011/04/25)
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- BACE1 inhibitors: Optimization by replacing the P1′ residue with non-acidic moiety
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Recently, we reported potent BACE1 inhibitors KMI-429, -684, and -574 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. These inhibitors showed potent inhibitory activities in enzymatic and cell assays, especially, KMI-429 was confirmed to significantly inhibit Aβ production in vivo. However, acidic moieties at the P4 and P1′ positions of KMI-compounds were thought to be unfavorable for membrane permeability across the blood-brain barrier. Herein, we replaced acidic moieties at the P4 position with other hydrogen bond acceptor groups, and these inhibitors exhibited improved BACE1 inhibitory activities in cultured cells. In this study, we replaced the acidic moieties at the P1′ position with non-acidic and low molecular sized moieties.
- Hamada, Yoshio,Abdel-Rahman, Hamdy,Yamani, Abdellah,Nguyen, Jeffrey-Tri,Stochaj, Monika,Hidaka, Koushi,Kimura, Tooru,Hayashi, Yoshio,Saito, Kazuki,Ishiura, Shoichi,Kiso, Yoshiaki
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p. 1649 - 1653
(2008/12/22)
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- Chemistry of superacids: 35. * NO2Cl-3MXN systems: Superelectrophilic aprotic nitrating agents for deactivated aromatics
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Superelectrophilic nitration of deactivated aromatics with NO2Cl-3MXn complexes in aprotic nonpolar solvents such as CH2Cl2 makes it possible to obtain the corresponding nitro derivatives in good to almost quantitative yields under mild conditions.
- Olah,Orlinkov,Ramaiah,Oxyzoglou,Prakash
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p. 924 - 927
(2007/10/03)
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- The oxidation of secondary alcohols by potassium tetraoxoferrate(VI)
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The kinetics of the oxidation of 2-propanol, 1,1,1-trifluoro-2-propanol, 1,1,1,3,3,3-hexafluoro-2-propanol, 1-phenyl-2,2,2-trifluoroethanol, 1-(4-methylphenyl)-2,2,2-trifluoroethanol, 1-(3-bromophenyl)-2,2,2-trifluoroethanol, and 1-(3-nitrophenyl)-2,2,2-trifluoroethanol by potassium tetraoxoferrate(VI) have been studied under basic conditions. The products are ketones, formed in almost quantitative yields, iron(III) hydroxide, and dioxygen. The reactions are characterized by substantial enthalpies of activation (40-60 kJ/mol), very unfavorable entropies of activation, large primary deuterium isotope effects, and a positive Hammett p value. Both acid and base catalysis are observed. Acid catalysis is attributed to formation of a more reactive oxidant, HFeO4-, at low pH. Base catalysis is attributed partly to the conversion of the reductants to alkoxide ions at high pH, and partly to the reaction of hydroxide ion with tetraoxoferrate(VI) to give a five-coordinated species, HOFeO43-, that reacts rapidly with nucleophiles. A reaction mechanism involving formation of an intermediate ferrate ester is proposed.
- Norcross, Bruce E.,Lewis, William C.,Gai, Huiffa,Noureldin, Nazih A.,Lee, Donald G.
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p. 129 - 139
(2007/10/03)
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- A novel non-acidic method for the preparation of 2,2,2-trifluoro-1-(3-nitrophenyl)ethanone and 1-nitro-3-trifluoromethylbenzene, versatile starting materials for trifluoromethyl-containing aromatic compounds
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Treatment of 2,2,2-trifluoro-1-phenylethanone (1) and α,α,α-trifluorotoluene (3) with ozone or ozonized air in chlorinated hydrocarbons in the presence of excess nitrogen dioxide and a catalytic amount of iron(III) salt at -10-0°C leads to the respective title nitro compounds 2 and 4 in good to excellent yields. The reaction is clean and rapid, little or no hydrolysis of the trifluoromethyl group being observed during the nitration.
- Suzuki,Tatsumi,Suzuki,Maeda
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p. 1353 - 1354
(2007/10/02)
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- Ozone-mediated Nitration of Aromatic Ketones and Related Compounds with Nitrogen Dioxide
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Alkyl aryl ketones react smoothly with nitrogen dioxide at low temperatures in the presence of ozone to give ortho- and meta-nitro derivatives as the principal products, the former usually being predominant (ortho:meta = 1.1-3.8:1.0).No attack was observed on the alkyl side chains.
- Suzuki, Hitomi,Murashima, Takashi
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p. 903 - 908
(2007/10/02)
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- Die Reacktionen von Bis(perfluoralkyl)cadmium-Komplexen mit Arylcarbonsaeurechloriden: Synthese von Aryl(perfluoralkyl)ketonen, (Perfluoralkyl-dihydropyridin)arylcarbonsaeureamiden, α,α-Bis(trifluormethyl)benzylalkoholen und Benzoesaeure-α,α-bis(trifluormethyl)benzylestern
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Perfluoroalkylcadmium complexes react with aroyl halides in the presence of strong bases such as pyridine to give the corresponding ketones ArCORf (which can be isolated in 5-51percent yield) and (perfluoroalkyldihydropyridine)aroylamides.The pure substances are obtained by chromatography.Aroyl fluorides and α,α-bis(trifluoromethyl)benzyl alcohols and benzoic acid-α,α-bis(trifluoromethyl)benzyl esters can be isolated as by-products.The dependency of the products formed on the kind of bases used as well as the reaction mechanisms are described.All products were identified by their 19F, 1H, 13C NMR, mass and IR spectra, and by elemental analysis.
- Naumann, Dieter,Finke, Martina,Lange, Horst,Dukat, Wolfgang,Tyrra, Wieland
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p. 215 - 237
(2007/10/02)
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