- Antioxidant building blocks I. The unexpected C-acetylation of 2,6-Di-tert-butylphenol with isopropenyl acetate
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While the reaction of some 2-substituted and 2,6-disubstituted phenols with isopropenyl acetate resulted in the corresponding phenol acetates, in the reaction of 2,6-di-tert-butylphenol, a useful starting material of antioxidant building blocks, under the same conditions 4-acetyl-2,6-di-tert-butylphenol was the only product.
- Gizur, Tibor,Ferenczy, Gyoergy G.,Agai-Csongor, Eva,Domany, Gyoergy
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- Synthesis, redox properties and antibacterial activity of hindered phenols linked to heterocycles
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A series of benzotriazole, cyclic amides and pyrimidine derivatives, containing 2,6-di-tert-butyl-phenol fragments, were synthesized. The redox properties of obtained compounds were studied using the cyclic voltammetry on a platinum electrode in acetonitrile. The oxidation potentials of all substances were comparable to those of BHT. The obtained compounds were tested for their antibacterial activity, and N-(2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-oxoethyl)isatin (32 μg/mL) exerted good activity against Staphylococcus aureus.
- Ivanova, Ludmila V.,Koshelev, Vladimir N.,Primerova, Olga V.,Vorobyev, Stepan V.
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- Synthesis and evaluation of dithiolethiones as novel cyclooxygenase inhibitors
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3H-1,2-Dithiole-3-thiones substituted with a 3,5-di-tert-butyl-4-hydroxyphenyl (DTBHP) or a 3,5-di-tert-butyl-4-methoxyphenyl group at the C5 position were prepared and their ability to inhibit the cyclooxygenase isoenzymes, COX-1 and COX-2 was evaluated. Both compounds were potent inhibitors of COX-2 (relative to rofecoxib), and while the phenol was a weak inhibitor of COX-1, the methyl ether gave no measurable inhibition. Docking studies of the two compounds into the COX-1 and -2 active sites showed that the methyl ether could only fit in the COX-2 active site whereas the phenol could be docked into both COX-1 and -2. This study reports a new mode for inhibitor binding to COX-1 and -2 and a novel structural scaffold for the development of COX-2 selective inhibitors.
- Zanatta, Shannon D.,Manallack, David T.,Jarrott, Bevyn,Williams, Spencer J.
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scheme or table
p. 459 - 461
(2011/03/20)
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- DITHIOLE COMPOUNDS AS COX INHIBITORS
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A compound of formula (I) wherein: R1 and R2 are the same or different and are independently selected from H and a shielding group; X and Y are each independently selected from N and CH; R3 is hydroxy, alkoxy, acyloxy or a
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Page/Page column 51-52
(2008/12/05)
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- Synthesis and biological evaluation of acyclic triaryl (Z)-olefins possessing a 3,5-di-tert-butyl-4-hydroxyphenyl pharmacophore: Dual inhibitors of cyclooxygenases and lipoxygenases
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A new class of regioisomeric acyclic triaryl (Z)-olefins possessing a 3,5-di-tert-butyl-4-hydroxyphenyl (DTBHP) 5-lipoxygenase (5-LOX) pharmacophore that is vicinal to a para-methanesulfonylphenyl cyclooxygenase-2 (COX-2) pharmacophore were designed for evaluation as selective COX-2 and/or 5-LOX inhibitors. The target compounds were synthesized via a highly stereoselective McMurry olefination cross-coupling reaction. This key synthetic step afforded a (Z):(E) olefinic mixture with a predominance for the (Z)-olefin stereoisomer. Structure-activity studies for the (Z)-1-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-(4-methanesulfonylphenyl)-1-phenylalk-1-ene regioisomers showed that COX-1 inhibition decreased, COX-2 inhibition increased, and the COX-2 selectivity index (SI) increased as the chain length of the alkyl substituent attached to the olefinic double bond was increased (Et → n-butyl → n-heptyl). In this group of compounds, inhibition of both 5-LOX and 15-LOX was dependent upon the length of the alkyl substituent with the hex-1-ene compound 9c having a n-butyl substituent exhibiting potent inhibition of both 5-LOX (IC50 = 0.3 μM) and 15-LOX (IC50 = 0.8 μM) relative to the inactive (IC50 > 10 μM) Et and n-heptyl analogs. Compound 9c is of particular interest since it also exhibits a dual inhibitory activity against the COX (COX-1 IC50 = 3.0 μM, and COX-2 IC50 = 0.36 μM, COX-2 SI = 8.3) isozymes. A comparison of the relative inhibitory activities of the two groups of regioisomers investigated shows that the regioisomers in which the alkyl substituent is attached to the same olefinic carbon atom (C-2) as the para-methanesulfonylphenyl moiety generally exhibit a greater potency with respect to COX-2 inhibition. The 4-hydroxy substituent in the 3,5-di-tert-butyl-4-hydroxyphenyl moiety is essential for COX and LOX inhibition since 3,5-di-tert-butyl-4-acetoxyphenyl derivatives were inactive inhibitors. These structure-activity data indicate acyclic triaryl (Z)-olefins constitute a suitable template for the design of dual COX-2/LOX inhibitors.
- Moreau, Anne,Praveen Rao,Knaus, Edward E.
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p. 5340 - 5350
(2008/02/07)
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- Retinoic acid receptor antagonist compounds and methods
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Trienoic compounds having activity as antagonists for retinoic acid receptors are provided. Also provided are pharmaceutical compositions incorporating such compounds and methods for their therapeutic use.
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- Synthesis and Electrochemical Characteristics of 1-(3,5-Di-tert-butyl-4-hydroxyphenyl)alkyl(aryl)ketones and Radicals Obtained Therefrom
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1-(3,5-Di-tert-butyl-4-hydroxyphenyl)alkyl(aryl) ketones were prepared by treating 2,6-di-tert-butylphenol with aliphatic acids anhydrides and aroyl chlorides. The products were characterized with IR and 1H NMR spectra. Electrochemical reductio
- Monastyrskaya,Lyutkin,Gorbunov,Klimov
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p. 1409 - 1416
(2007/10/03)
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- Pharmaceutically active bicyclic-heterocyclic amines
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The pharmaceutically active bicyclic heterocyclic amines (XXX) STR1 where W1 is --N= or --CH=; W3 is --N= or --CH=; W5 is --N= or --CR5 -- with the proviso that W5 is --CR5 -- when both W1 and W3 are --N= which are useful as pharmaceuticals in treating mild and/or moderate to severe head injury, subarachnoid hemorrhage and subsequent ischemic stroke, asthma and reduction of mucous formation/secretion in the lung and other diseases and injuries.
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- Functionalized tris(hydroxyphenyl) compounds
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Compounds useful as polymer stabilizers which are polymerizable into condensation polymer systems are disclosed and claimed. A particularly preferred embodiment is 1-(3'-(benzotriazol-2"-yl)-4'-hydroxyphenyl)-1,1-bis(4-hydroxyphenyl)ethane.
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- Aryl-substituted rhodanine derivatives
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Provided are certain aryl-substituted rhodanine derivatives, treatment methods and pharmaceutical formulations thereof.
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- Method of treating type I diabetes
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Provided is a method for treating Type I diabetes in mammals utilizing certain aryl-substituted rhodanine derivatives.
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- Novel anti-inflammatory agents, pharmaceutical compositions and methods for reducing inflammation
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The present invention relates to novel specifically-substituted phenyl compounds, especially substituted di-tert-butyl phenol derivatives, which are effective as anti-inflammatory, analgesic and/or antipyretic agents. These phenyl compounds are substituted with a low molecular weight alkyl chain which terminates in a specific unsaturated functional group. These unsaturated functionalities are --C CH, C=CH2, C=C=CH2, and aldehydes in the form of their acetals. The present invention further relates to pharmaceutical compositions which contain an anti-inflammatory agent of the present invention and a pharmaceutically-acceptable carrier. Finally, the present invention relates to methods for treating diseases characterized by inflammation, such as rheumatoid arthritis and osteoarthritis, in humans or lower animals. Such methods comprise administering to a human or lower animal in need of such treatment a safe and effective amount of an anti-inflammatory agent or composition of the present invention.
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- Oxygenation of tert-Butylphenols with an Unsaturated Side Chain
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Base- and Co(Salpr)-promoted oxygenations of title compounds have been investigated with a view to obtaining further details concerning controlling factors in regioselective O2 incorporation into phenols.In the oxygenation of 4-alkenyl-2,6-di-tert-butyl- and 2-alkenyl-4,6-di-tert-butylphenols (1 and 12), the reactivity of the substrates and regioselectivity in the O2 incorporation may be interpreted in terms of electronic and steric effects of the alkenyl group as well as association effect of the countercation K+ on the transition-state 26 involving a charge transfer from the substrate anion to O2.With 4-alkynyl-2,6-di-tert-butylphenols (21), dioxygen was incorporated exclusively into the ortho position only when the phenolate anion was associated with K+.On the contrary, in the oxygenation of 1 and 12 with Co(Salpr), O2 was incorporated exclusively into the alkynyl side chain, regardless of the nature of the substituent, whereas with 21, O2 incorporation was distributed to both the ortho and the alkenyl side chain.The substituent-dependent regioselectivity in the oxygenation of phenols with Co(Salpr) is because the reactive phenolate-COIII species undergo homolysis to form phenoxy radical-CoII species reversibly, whose oxygenations compete with each other.When the oxygenation of the anionic species predominates, O2 is incorporated into the ortho position, whereas with the radical species the para and side chain oxydations predominate.
- Nishinaga, Akira,Iwasaki, Hitoshi,Shimizu, Tadashi,Toyoda, Yasushi,Matsuura, Teru
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p. 2257 - 2266
(2007/10/02)
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- Oxygenation of 2,6-Di-tert-butylphenols Bearing an Electron-Withdrawing Group in the 4-Position
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Co(Salpr), a five-coordinate cobalt (II) Schiff base complex, has been found to promote oxygenation of 2,6-di-tert-butylphenols bearing an electron-withdrawing group in the 4-position, leading to dioxygen incorporation exclusively into the ortho position of the phenols. 4-Acyl-2,6-di-tert-butylphenols (1) and their oxime O-methyl ethers (2) gave the corresponding 6-hydroperoxy-2,4-cyclohexadienone derivatives 3 and 4 quantitatively.Schiff bases 10 derived from 3,5-di-tert-butyl-4-hydroxybenzaldehyde, on the other hand, gave unexpected products, 1,2-dihydropyridine derivatives 11, cyclopentadienone 12, and epoxy-o-quinol 13.The structure of dihydropyridine 11a was determined by X-ray analysis. 2,6-Di-tert-butyl-4-cyanophenol gave 2,5-di-tert-butyl-3-cyano-2,4-cyclopentadienone in good yield.The formation of these products can be understood to result from intramolecular decomposition of the corresponding o-peroxidic intermediate.Phenols 2 were readily oxygenated in t-BuOH containing t-BuOK to give epoxy-o-quinols 7 in excellent yield, although the other phenols examined were unsusceptible to oxygenation under various basic conditions.
- Nishinaga, Akira,Shimizu, Tadashi,Toyoda, Yasushi,Matsuura, Teruo,Hirotsu, Ken
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p. 2278 - 2285
(2007/10/02)
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- OXYGENATION OF 2,6-DI-t-BUTYLPHENOLS BEARING ELECTRON-WITHDRAWING GROUP AT 4-POSITION MEDIATED BY CO(II)-SCHIFF BASE COMPLEX
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4-Acyl-2,6-di-t-butylphenols except 3,5-di-t-butyl-4-hydroxybenzaldehyde were oxygenated in the presence of Co(Salpr) exclusively at the ortho position to give the corresponding 3,5-di-t-butyl-6-hydroperoxy-2,4-cyclohexadienone derivatives in quantitative
- Nishinaga, A.,Shimizu, T.,Matsuura, T.
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p. 5293 - 5296
(2007/10/02)
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- UNUSUAL DISPROPORTIONATION ENCOUNTERED IN THE ALUMINA-CATALYZED DEHYDRATION OF 4-(α-HYDROXYETHYL)PHENOLS
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Alumina-catalyzed dehydrations of 4-(α-hydroxyethyl)phenols provided unusual disproportionation products: 4-ethylphenols and 4-acetylphenols and their tautomers.
- Kamogawa, Hiroyoshi,Watanabe, Motoshi,Oka, Saichiro,Nanasawa, Masato
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p. 793 - 794
(2007/10/02)
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- REACTION OF SUPEROXO Co(III) COMPLEXES WITH 2,6-DI-t-BUTYL-p-BENZOQUINONE METHIDES
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Superoxo Co(III) complexes derived from Co(Salpr) and (3-) reacted with 2,6-di-t-butyl-p-benzoquinone methides to give 2,6-di-t-butyl-p-benzoquinone and 2,6-di-t-butyl-2,5-cyclohexadienonespirooxiranes as the main products, which are considered to result from nucleophilic attack by superoxo species on the exo double bond of the quinone methides.
- Nishinaga, A.,Tomita, H.,Tarumi, Y.,Matsuura, T.
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p. 4849 - 4852
(2007/10/02)
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- Process for preparing hindered alkenyl phenols
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Hindered alkenyl phenols, all of which can be used as antioxidants, and some of which can be used as monomers, can be prepared by the dehydrohalogenation of the α-haloalkyl phenol.
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