- Competitive Binding Assay with an Umbelliferone-Based Fluorescent Rexinoid for Retinoid X Receptor Ligand Screening
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Ligands for retinoid X receptors (RXRs), "rexinoids", are attracting interest as candidates for therapy of type 2 diabetes and Alzheimer's and Parkinson's diseases. However, current screening methods for rexinoids are slow and require special apparatus or facilities. Here, we created 7-hydroxy-2-oxo-6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2H-chromene-3-carboxylic acid (10, CU-6PMN) as a new fluorescent RXR agonist and developed a screening system of rexinoids using 10. Compound 10 was designed based on the fact that umbelliferone emits strong fluorescence in a hydrophilic environment, but the fluorescence intensity decreases in hydrophobic environments such as the interior of proteins. The developed assay using 10 enabled screening of rexinoids to be performed easily within a few hours by monitoring changes of fluorescence intensity with widely available fluorescence microplate readers, without the need for processes such as filtration.
- Yamada, Shoya,Kawasaki, Mayu,Fujihara, Michiko,Watanabe, Masaki,Takamura, Yuta,Takioku, Maho,Nishioka, Hiromi,Takeuchi, Yasuo,Makishima, Makoto,Motoyama, Tomoharu,Ito, Sohei,Tokiwa, Hiroaki,Nakano, Shogo,Kakuta, Hiroki
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p. 8809 - 8818
(2019/10/11)
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- aromatic compound having fused cyclic substituent in aromatic ring and organic light-emitting diode including the same
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The present invention relates to a compound having a cyclic substituent fused with a cyclic ring and an organic light emitting diode including the same, and more particularly, to a compound for an organic light emitting diode represented by chemical formula A and an organic light emitting diode including the same. In chemical formula A, X is a substituent having structural formula X, Y is a substituent of structural formula Y1, n is an integer from 1 to 4, and structural formulas X and Y1 are the same as described in detailed description of the present invention.
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Paragraph 0295-0297
(2019/01/06)
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- The synthesis of lactone-bridged 1,3,5-triphenylbenzene derivatives as pi-expanded coumarin triskelions
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Two triply lactone-bridged 1,3,5-triphenylbenzene derivatives with solubilizing moieties have been synthesized in five and six steps from commercially available starting materials. Compounds containing the 1,3,5-triphenylbenzene core with two atom bridges are relatively unknown. This new class of pi-expanded coumarins contain triskelion architectures and X-ray crystallographic studies of one of the triskelions indicates that the 1,3,5-triphenylbenzene core adopts a near-planar geometry. This is the only known example of a two atom-bridged 1,3,5-triphenylbenzene derivative to adopt a planar structure.
- Hintz, Heather A.,Sortedahl, Nicholas J.,Meyer, Samantha M.,Decato, Daniel A.,Dahl, Bart J.
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supporting information
p. 4703 - 4708
(2017/11/17)
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- aromatic compound having fused cyclic substituent in aromatic ring and organic light-emitting diode including the same
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The present invention refers to to the aromatic ring-fused ring withdrawing substituent and a compound having an same relates to organic light emitting device including, more specifically a represented by [formula A] an alkali-soluble polymer resin compound for an organic light-emitting device including organic light emitting device is characterized in that the. [Formula A] In said [formula A], X has a dementia drug; and shows strong X having substituted group, Y has a dementia drug; and shows strong formula selected from the group consisting Y1 to Y5 having one of substituted group, the n being integers, of 4 to 1, the Y5 formula to Y1 formula and X formula detailed description of the invention is described. (by machine translation)
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Paragraph 0307; 0308
(2016/10/10)
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- Selective arylation and vinylation at the α position of vinylarenes
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In intermolecular Heck reactions of styrene and vinylarenes, the aryl and vinyl groups routinely insert at the β position. However, selective insertion at the α position has been very rare. Herein, we provide a missing piece in the palette of Heck reaction, which gave >20:1 α selectivity. The key to our success is a new ferrocene 1,1′-bisphosphane (dnpf) that carries 1-naphthyl groups. Our mechanistic studies revealed that the high α selectivity is partly attributable to the steric effect of dnpf. The rigid and bulky 1-naphthyl groups of dnpf sterically disfavor β insertion. What the Heck! In intermolecular Heck reactions, insertion at the β position of aromatic olefins is very common, but reversal of the selectivity for selective α insertion has been a longstanding problem. A general method to couple aryl and vinyl triflates with aromatic olefins in >20:1 α selectivity is presented. The key to this successful approach is a new ferrocene bisphosphane with naphthyl groups on the phosphorus atom (see scheme; OTf=triflate). Copyright
- Zou, Yinjun,Qin, Liena,Ren, Xinfeng,Lu, Yunpeng,Li, Yongxin,Zhou, Jianrong
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supporting information
p. 3504 - 3511
(2013/07/05)
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- Modeling, synthesis, and biological evaluation of potential retinoid X receptor (RXR) selective agonists: Novel analogues of 4-[1-(3,5,5,8,8- Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) and (E)-3-(3-(1,2,3,4-tetrahydro-1,1,
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Three unreported analogues of 4-[1-(3,5,5,8,8-pentamethyl-5-6-7-8- tetrahydro-2-naphthyl)ethynyl]benzoic acid (1), otherwise known as bexarotene, as well as four novel analogues of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6- pentamethylnaphthalen-7-yl)-4-hydr
- Jurutka, Peter W.,Kaneko, Ichiro,Yang, Joanna,Bhogal, Jaskaran S.,Swierski, Johnathon C.,Tabacaru, Christa R.,Montano, Luis A.,Huynh, Chanh C.,Jama, Rabia A.,Mahelona, Ryan D.,Sarnowski, Joseph T.,Marcus, Lisa M.,Quezada, Alexis,Lemming, Brittney,Tedesco, Maria A.,Fischer, Audra J.,Mohamed, Said A.,Ziller, Joseph W.,Ma, Ning,Gray, Geoffrey M.,Van Der Vaart, Arjan,Marshall, Pamela A.,Wagner, Carl E.
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p. 8432 - 8454
(2013/12/04)
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- THERAPEUTIC COMPOUNDS
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The invention provides compounds of formulae (I), (II), (III), and (IV): and salts thereof, as well as pharmaceutical compositions comprising such compounds. The compounds are useful for treating cancers and Alzheimer's disease.
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Page/Page column 36
(2013/03/28)
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- Retinoid compounds and their use
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The invention relates to retinoid compounds of the formula (I): wherein V is a hydrophobic group;W is a non-polyenic linker; andX is a polar group comprising a hydrogen bond donor; or a salt thereof, and to the use of such compounds in the control of cell differentiation.
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- Process for preparing retinoid compounds
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The application claims a process for the preparation of a RAR modulator according to formula Ia or Ib comprising to sequential Heck couplings steps to elaborated the disubstituted olefin.
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Page/Page column 6-7
(2008/06/13)
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- Retinoid compounds (I)
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The current invention provide novel retinoid compounds and methods for their synthesis, methods of treating or preventing emphysema, cancer and dermatological disorders and pharmaceutical compositions suitable for the treatment or prevention of emphysema, cancer and dermatological disorders.
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- Synthesis of novel retinoid X receptor-selective retinoids
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Retinoids 1-5 have been identified as potent RXR agonists for evaluation in the treatment of non-insulin-dependent (type II) diabetes mellitus (NIDDM). Highly convergent syntheses of 1-5 have been developed. The core tetrahydronaphthalene 7, employed in the synthesis of 1 and 2, was prepared in 98% yield using an AlCl3-catalyzed (0.03 equiv) Friedel-Crafts alkylation of toluene with 2,5-dichloro-2,5-dimethylhexane 6. A nitromethane-mediated Fridel-Crafts acylation of 7 with chloromethylnicotinate 9 was developed to prepare ketone 10 in 68% yield. Chelate-controlled addition of MeMgCl to 10 followed by dehydration afforded olefin 11 in 65% yield. Cyclopropanation of 11 with trimethylsulfoxonium ylide, followed by saponification, completed a five-step synthesis of 1 in 33% yield. FeCl3-catalyzed (0.05 equiv) Friedel-Crafts acylation of 7 with chloromethyl-terephthalate 14 afforded ketone 15 in 81% yield. Saponification of 15 and reaction with 50% aqueous NH2OH in AcOH afforded a 9:1 mixture of cis and trans oximes, from which the desired cis-oxime 2 was isolated in 43% yield. The core bromo-dihydronaphthalene 29 required for the synthesis of 3-5 was prepared by a Shapiro reaction. Transmetalation of 29 and reaction with Weinreb amides 30b or 36 afforded ketones 32 and 37, which were converted into 3-5 using chemistry comparable to the tetrahydronaphthylene series. Suzuki coupling of boronic acids 41 and 42 with vinyl triflate 43 provided an alternative approach to the synthesis of this class of compounds.
- Faul,Ratz,Sullivan,Trankle,Winneroski
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p. 5772 - 5782
(2007/10/03)
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- Biphenyl derivatives substituted by an aromatic or heteroaromatic radical and pharamaceutical and cosmetic compositions containing same
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“Biphenyl derivatives substituted with an aromatic or heteroaromatic radical, and pharmaceutical and cosmetic compositions containing them” in which: Ar represents an aromatic or a heteroaromatic radical optionally substituted, in particular, with an alkyl or a carboxyl group, R2and R3represent, in particular, H or alkyl, or R2and R3, taken together, form a 5- or 6-membered ring, R4and R5represent, in particular, H or halogen, R6represents, in particular, H or lower alkyl, and the salts of the compounds of formula (I). These compounds can be used in particular in the treatment of dermatological complaints associated with a keratinization disorder, and for combating ageing of the skin.
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- Polyaromatic propynyl compounds and pharmaceutical/cosmetic compositions comprised thereof
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Novel pharmaceutically/cosmetically-active polyaromatic propynyl compounds have the structural formula (1): STR1 in which X is one of the radicals: STR2 and are useful for the treatment of a wide variety of disease states, whether human or veterinary, for example dermatological, rheumatic, respiratory, cardiovascular and ophthalmological disorders, as well as for the treatment of mammalian skin and hair conditions/disorders.
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- A novel synthesis of 9,13-dicis double bonds locked retinoids
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Synthesis of two retinoids in which the 9,13-dicis double bonds were locked in cycloalkene or thiophene was described. The key step was carbonylation of vinyl bromide 9 and 16 with carbon monoxide in the presence ofPd(PPh3)4.
- Qing, Feng-Ling,Yue, Xiang-Jun
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p. 8067 - 8070
(2007/10/03)
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- Conformational effects on retinoid receptor selectivity. 2. Effects of retinoid bridging group on retinoid X receptor activity and selectivity
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The natural retinoid 9-cis-retinoic acid is an activating ligand for both the retinoic acid receptors (BARs) and the retinoid X receptors (RXRs), which are members of the retinoid/thyroid hormone/steroid hormone family of nuclear receptor proteins that activate gene transcription through specific response elements. The pharmacophoric groups necessary to confer RXR selectivity were established by evaluating the ability of 21 conformationally restricted retinoids to activate the TREpal retinoic acid receptor response element for gene transcription in the presence of one of the three PAR subtypes or RXRα. In contrast to those retinoids selective for the RARs, these RXR-selective retinoids have one less atom in the bridge linking the hydrophobic and carboxylic acid termini of the retinoid skeleton. Therefore, a one-carbon bridge replaces the 19-methyl group and 9E-double bond of 9-cis-retinoic acid and is further functionalized by inclusion in an isopropylidene group, a dioxolane ring, or a cyclopropane ring for optimal RXRα activity and selectivity. In addition, the β-geranylidene and 20-methyl-(11E,13E)- dienoic acid groups of 9-cis-retinoic acid are replaced by a 5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl ring and a 4-carboxylphenyl ring, respectively, for optimal activation and selectivity. RXRα selectivity is reduced on replacement of the 4-carboxylphenyl group by a 2-carboxyl-5- thienyl group or the 9-cis-retinoic acid methylpentadienoic acid terminus.
- Dawson,Jong,Hobbs,Cameron,Chao,Pfahl,Lee -,Shroot,Pfahl
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p. 3368 - 3383
(2007/10/03)
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- Effect of structural modifications in the C7-C11 region of the retinoid skeleton on biological activity in a series of aromatic retinoids
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A series of conformationally restricted analogues of (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)propent yl]benzoic acid - (E)-4-[1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtalenyl)-2-propt enyl]benzoic acid, (E)-4-[3-(5,6,7,8-tet
- Dawson,Hobbs,Derdzinski,Chao,Frenking,Loew,Jetten,Napoli,Williams,Sani,Wille Jr.,Schiff
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p. 1504 - 1517
(2007/10/02)
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