- Phosphine-Catalyzed Difunctionalization of β-Fluoroalkyl α,β-Enones: A Direct Approach to β-Amino α-Diazo Carbonyl Compounds
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An efficient and practical phosphine-catalyzed vicinal difunctionalization of β-fluoroalkyl α,β-enones with TMSN3 has been developed. Using dppb as the catalyst, the reaction worked efficiently to yield various β-amino α-diazocarbonyl compounds in high yields (up to 94 %). This work marks the first efficient construction of α-diazocarbonyl compounds by phosphine catalysis. Meanwhile, the asymmetric variant induced by the nucleophilic bifunctional phosphine P4 led to various chiral fluoroalkylated β-amino α-diazocarbonyl compounds in high yields and enantioselectivity. NMR and ESI-MS studies support the existence of the key reaction intermediates. In contrast, β-azide carbonyl compounds would be furnished in good yields from β-fluoroalkylated β,β-disubstituted enones.
- Wang, Huamin,Zhang, Li,Tu, Youshao,Xiang, Ruiqi,Guo, Yin-Long,Zhang, Junliang
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- COMPOUNDS AND SYNTHETIC METHODS FOR THE PREPARATION OF RETINOID X RECEPTOR-SPECIFIC RETINOIDS
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Provided herein are compounds useful for the preparation of compounds that have retinoid-like biological activity. Also provided herein are processes for the preparation of compounds that have retinoid-like biological activity.
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Paragraph 148; 151
(2019/06/05)
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- COMPOUNDS AND METHODS FOR INHIBITING CYP26 ENZYMES
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Compounds described herein are inhibitors of retinoic acid inducible P450 (CYP26) enzymes, and are useful for treating diseases that are responsive to retinoids. Certain compounds have retinoid activity, are resistant to CYP26-mediated catabolism, and are used for treating diseases that are responsive to retinoids.
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Page/Page column 17
(2018/07/05)
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- Design, synthesis and anticancer biological evaluation of novel 1,4-diaryl-1,2,3-triazole retinoid analogues of tamibarotene (AM80)
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We report herein the design and synthesis via click chemistry of twelve novel triazole retinoid analogues of tamibarotene (AM80) and the evaluation of their anticancer activities against six cancer cell lines: HL60, K562, 786, HT29, MCF7 and PC3. Among the synthesized compounds, two were more potent than tamibarotene against solid tumor cells, and one of them had similar potency to tamibarotene against HL60 cells. The bioisosteric exchange between the amide group and the 1,2,3-triazole core in the retinoid agent tamibarotene (AM80) reported in this work is a valid strategy for the generation of useful compounds against cancer.
- Aleixo, Mariana A. A.,Garcia, Taís M.,Carvalho, Diego B.,Viana, Luiz H.,Amaral, Marcos S.,Kassab, Najla M.,Cunha, Marilin C.,Pereira, Indiara C.,Guerrero, Palimécio G,Perdomo, Renata T.,Matos, Maria F. C.,Baroni, Adriano C. M.
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p. 109 - 124
(2017/12/08)
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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 0280-00282
(2019/01/06)
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- EXPANSION OF RENEWABLE STEM CELL POPULATIONS
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Ex vivo and in vivo methods of expansion of renewable stem cells, expanded populations of renewable stem cells and their uses.
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Paragraph 0514
(2016/05/02)
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- Benzocarbazoles dioxane derivatives, its preparation process and its use in medicine
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The invention relates to a benzodioxane derivative, a preparation method thereof and application of the derivative in medicines. Specifically, the invention relates to a novel benzodioxane derivative shown as a formula (I), medial salt thereof or a medicine composition containing the derivative, and a preparation method of the derivative. The invention further relates to a use of the benzodioxane derivative and the medial salt thereof or the medicine composition containing the derivative in preparing therapeutic agent, especially GPR 40 agonist, and a drug for treating the diseases such as diabetes, metabolic disorders and the like, wherein each substituent group in the formula (I) is as defined in the description.
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Paragraph 0352; 0355; 0359-0361
(2016/10/10)
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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 0292; 0293
(2016/10/10)
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- Organosilicon compounds as adult T-cell leukemia cell proliferation inhibitors
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Aggressive forms of adult T-cell leukemia (ATL) respond poorly to conventional anticancer chemotherapy, and new lead compounds are required for the development of drugs to treat this fatal disease. Recently, we developed ATL cell-selective proliferation inhibitors based on a tetrahydrotetramethylnaphthalene (TMN) skeleton 1, and here we report the design and synthesis of silicon analogs of TMN derivatives. Among them, compound 13 showed the most potent growth-inhibitory activity towards the ATL cell line S1T, though its selectivity for S1T over the non-ATL cell line MOLT-4 was only moderate. This result, as well as computational studies, suggests that sila-substitution (C/Si exchange) is useful for structure optimization of these inhibitors.
- Nakamura, Masaharu,Matsumoto, Yotaro,Toyama, Masaaki,Baba, Masanori,Hashimoto, Yuichi
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p. 237 - 241
(2013/03/14)
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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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- Synthesis of arotinoid acid and temarotene using mixed (Z)-1,2- bis(organylchalcogene)-1-alkene as precursor
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An efficient and novel total synthesis of the two bioactive retinoids temarotene and arotinoid acid (TTNPB) is described. The key steps in this process include the regio and stereoselective hydrotelluration of thioacetylene 9 and Te/Li transmetalation of mixed (Z)-1,2-bis(organylchalcogene)-1-alkene (Z)-3. The subsequent reaction involving the β-phenylthio vinyl lithiated intermediate 10 with dimethyl sulfate gave the (E)-vinyl sulfide 11. The Ni +2 cross-coupling of 11 with the corresponding phenylzinc bromide and p-oxazoline phenylzinc bromide 12 afforded the respective temarotene 2 and retinoid-oxazoline substituted 13. Finally, compound 13 was deprotected with HCl to furnish arotinoid acid (TTNPB) 1.
- Guerrero Jr., Palimécio G.,De Oliveira, Paulo R.,Baroni, Adriano C.M.,Marques, Francisco A.,Labes, Ricardo,Hurtado, Gabriela R.,Dabdoub, Miguel J.
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p. 5302 - 5305
(2012/11/13)
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- Synthesis and evaluation of synthetic retinoid derivatives as inducers of stem cell differentiation
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All-trans-retinoic acid (ATRA) and its associated analogues are important mediators of cell differentiation and function during the development of the nervous system. It is well known that ATRA can induce the differentiation of neural tissues from human pluripotent stem cells. However, it is not always appreciated that ATRA is highly susceptible to isomerisation when in solution, which can influence the effective concentration of ATRA and subsequently its biological activity. To address this source of variability, synthetic retinoid analogues have been designed and synthesised that retain stability during use and maintain biological function in comparison to ATRA. It is also shown that subtle modifications to the structure of the synthetic retinoid compound impacts significantly on biological activity, as when exposed to cultured human pluripotent stem cells, synthetic retinoid 4-(5,5,8,8-tetramethyl-5,6,7,8- tetrahydronaphthalen-2-ylethynyl)benzoic acid, 4a (para-isomer), induces neural differentiation similarly to ATRA. In contrast, stem cells exposed to synthetic retinoid 3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylethynyl)benzoic acid, 4b (meta-isomer), produce very few neurons and large numbers of epithelial-like cells. This type of structure-activity-relationship information for such synthetic retinoid compounds will further the ability to design more targeted systems capable of mediating robust and reproducible tissue differentiation.
- Christie, Victoria B.,Barnard, Jonathan H.,Batsanov, Andrei S.,Bridgens, Caroline E.,Cartmell, Emily B.,Collings, Jonathan C.,Maltman, Daniel J.,Redfern, Christopher P. F.,Marder, Todd B.,Przyborski, Stefan,Whiting, Andrew
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experimental part
p. 3497 - 3507
(2009/02/05)
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- 5-[PHENYL-TETRAHYDRONAPHTHALENE-2-YL DIHYDRONAPHTHALEN-2-YL AND HETEROARYL-CYCLOPROPYL]-PENTADIENOIC ACID DERIVATIVES HAVING SERUM GLUCOSE REDUCING ACTIVITY
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Compounds of the formula where the variables have the meaning defined in the specification are capable of reducing serum glucose levels in diabetic mammals without the undesirable side effects of reducing serum thyroxine levels and transiently increasing triglyceride levels.
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- Stereoselective synthesis of tetrazole CB92834, a potent retinoid compound
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An improved, convergent synthesis of CB92834 is relying on a Suzuki cross-coupling reaction and easily allows multigram-scale preparation of the compound. The approach features three highly stereoselective steps.
- Garipova, Goulnara,Gautier, Arnaud,Piettre, Serge R.
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p. 4755 - 4759
(2007/10/03)
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- Synthesis of the trifluoromethylated retinoial aromatic amide - 4-[1-(5,6,7,8-tetrahydro-3-trifluoromethyl-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl]benzoic acid
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A new methodology was developed for the preparation of an o-trifluoromethylated arylamine. The condensation of 2-amino-3-trifluoromethyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene and terephthalic acid monomethyl ester chloride gave the trifluoromethylated retinoial aromatic amide. The key step in the synthesis is the introduction of the aryl trifluoromethyl group.
- Qing, Feng-Ling,Fan, Junfa
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p. 159 - 161
(2007/10/03)
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- Retinoids, methods for their production and use
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Dienoic retinoids having activity for retinoid X receptors or are panagonists on retinoic acid receptors and retinoid X receptors are provided. Also provided are pharmaceutical compositions incorporating such compounds and methods for their therapeutic us
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- A Suzuki coupling approach to trifluoromethyl derivative of targretin (LGD 1069)
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The palladium-catalyzed Suzuki coupling reaction σ-trinuoromethylated arylboronic acid 4 and vinyl triflate 5 provided the trifluoromethyl derivative of Targretin (LGD1069).
- Qing, Feng-Ling,Fan, Junfa
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p. 2117 - 2120
(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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- Tetrahydronaphthyl and thiazole, oxazole or imidazole substituted ethene derivatives having retinoid-like activity, reduced skin toxicity and reduced teratogenecity
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Compounds of the formula STR1 as herein defined, have retinoid-like activity and are substantially non-teratogenic and non-irritating to the skin.
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- Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids
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Two series of potent retinoid X receptor (RXR)-selective compounds were designed and synthesized based upon recent observation that (E)-4-[2- (5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB) binds and transactivates only the retinoic acid receptor (RAR) subtypes whereas (E)-4-[2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2- naphthalenyl)-1-propenyl]benzoic acid (3-methyl TTNPB) binds and transactivates both the RAR and RXR subfamilies. Addition of functional groups such as methyl, chloro, bromo, or ethyl to the 3-position of the tetrahydronaphthalene moiety of 4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro- 2-naphthyl)carbonyl]benzoic acid (5a) and 4-[1-(5,5,8,8-tetramethyl-5,6,7,8- tetrahydro-2-naphthyl)ethenyl]benzoic acid (6a) results in compounds which elicit potent and selective activation of the RXR class. Such RXR-selective compounds offer pharmacological tools for elucidating the biological role of the individual retinoid receptors with which they interact. Activation profiles in cotransfection and competitive binding assays as well as molecular modeling calculations demonstrate critical structural determinants that confer selectivity for members of the RXR subfamily. The most potent compound of these series, 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2- naphthyl)ethenyl]benzoic acid (6b), is the first RXR-selective retinoid (designated as LGD1069) to enter clinical trials for cancer indications.
- Boehm,Zhang,Badea,White,Mais,Berger,Suto,Goldman,Heyman
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p. 2930 - 2941
(2007/10/02)
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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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- Retinobenzoic Acids. 1. Structure-Activity Relationships of Aromatic Amides with Retinoidal Activity
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Two types of aromatic amides, terephthalic monoanilides and (arylcarboxamido)benzoic acids, have been shown to possess potent retinoidal activities and can be classified as retinoids.The structure-activity relationships of these amides are discussed on the basis of differentiation-inducing activity on human promyelocytic leukemia cells HL-60.In generic formula 4 (X = NHCO or CONH), the necessary factors to elicit the retinoidal activities are a medium-sized alkyl group (isopropyl, tert-butyl, etc.) at the meta position and a carboxyl group at the para position of the other benzene ring.The bonding of the amide structure can be reversed, this moiety apparently having the role of locating the two benzene rings at suitable positions with respect to each other.Substitution at the ring position ortho to the amide group or N-methylation of the amido group caused loss of activity, presumably owing to the resultant change of conformation.It is clear that the mutual orientation of the benzylic methyl group(s) and the carboxyl group and their distance apart are essential factors determining the retinoidal activity.Among the synthesized compounds, 4-benzoic acid (Am80) and 4-benzoic acid (Am580) were several times more active than retinoic acid in the assay.They are structurally related to retinoic acid, as is clear from the biological activity of the hybrid compounds (M2 and R2).
- Kagechika, Hiroyuki,Kawachi, Emiko,Hashimoto, Yuichi,Himi, Toshiyuki,Shudo, Koichi
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p. 2182 - 2192
(2007/10/02)
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