- Synthesis and Photoswitching Properties of Bioinspired Dissymmetric I-Pyrone, an Analogue of Cyclocurcumin
-
Cyclocurcumin (CC), a turmeric curcuminoid with potential therapeutic properties, is also a natural photoswitch that may undergo E/Z photoisomerization under UV light. To be further exploited in relevant biological applications, photoactivation under near-infrared (NIR) irradiation is required. Such requirement can be met through opportune chemical modifications, by favoring two-photon absorption (TPA) probability. Herein, a general and efficient synthesis of a biomimetic 2,6-disubstituted-δ-pyrone analogue of CC is described, motivated by the fact that molecular modeling previews an order of magnitude increase of its NIR TPA compared to CC. Three retrosynthetic pathways have been identified (i) via an aryl-oxazole intermediate or via aryl-diynone through (ii) a bottom-up or (iii) a top-down approach. While avoiding the passage through unstable synthons or low-yield intermediate reactions, only the latest approach could conveniently afford the 2,6-disubstituted-I-pyrone analogue of CC, in ten steps and with an overall yield of 18%. The photophysical properties of our biomimetic analogue have also been characterized showing an improved photoisomerization yield over the parent natural compound. The potentially improved nonlinear optical properties, as well as enhanced stability, may be correlated to the enforcement of the planarity of the pyrone moiety leading to a quadrupolar D-π-A-π-D system.
- Pecourneau, Jérémy,Losantos, Raúl,Monari, Antonio,Parant, Stéphane,Pasc, Andreea,Mourer, Maxime
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p. 8112 - 8126
(2021/06/30)
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- Process for preparing flavonoid derivatives and the intermediate thereof
-
The present invention provides: a method for manufacturing a flavonoid derivative using a reaction for synthesizing a chalcone derivative by a protection/deprotection reaction of a hydroxyl group and an aldol condensation reaction; and an intermediate thereof. By the method for manufacturing the flavonoid derivative of the present invention can manufacture the flavonoid derivative such as velutin and homoeriodictyol, the present invention can be usefully used in industrial fields such as cosmetics requiring mass production of flavonoid derivatives.
- -
-
Paragraph 0112; 0117-0119
(2020/10/03)
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- STYRYLBENZOTHIAZOLE DERIVATIVES AND USES IN IMAGING
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This disclosure relates to styrylbenzothiazole derivatives for use as in vivo imaging agents for the diagnosis of Parkinson's disease (PD) or other degenerative disorders or conditions of the central nervous system. Early diagnosis is particularly advantageous as neuroprotective treatment can be applied to healthy neural cells to delay or even prevent the onset of debilitating clinical symptoms.
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Page/Page column 5; 39
(2019/12/04)
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- Method for synthesizing compound Paulownione C and Tomentodiplone O
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The invention relates to a method for synthesizing natural products Tomentodiplacone O and Paulownione C. The method adopts 2, 4, 6-Trihydroxyacetophenone monohydrate compound, citral, clove aldehydeand vanillin as initial raw materials, general inorganic alkali as a catalyst, and methanol with low toxicity as a solvent; high-toxicity pyridine is avoided, and two natural products Tomentodiplone Oand Paulownione C are prepared through five steps. The method has the advantages of simple synthetic route, simple operation, green and high efficiency, thereby solving the problem of high toxicity and low yield of the prepared benzopyran compound, and the method has certain industrial economic value.
- -
-
Paragraph 0028; 0034; 0035
(2019/06/13)
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- Drug compound for treating hepatopathy and application thereof
-
The invention discloses a drug compound for treating hepatopathy and application thereof. The drug compound specifically serves as a compound shown in general formula (I) or an optical isomer or a pharmaceutically-acceptable salt of the compound. The compound or the optical isomer or the pharmaceutically-acceptable salt of the compound has a good curative effect and low toxicity on hepatopathy, especially fatty liver. Experiments show that the compound has an obvious protective effect on zebrafish nonalcoholic fatty liver, so that the drug compound has a good application prospect in medicinesfor treatment or prevention of hepatopathy, especially fatty liver or liver fibrosis or liver cirrhosis.
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-
Paragraph 0244-0246
(2019/10/15)
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- General approach to neolignan-core of the boehmenan natural product family
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Abstract: A novel approach to the neolignan-core skeletons of boehmenan natural products and to dehydrodiconiferyl alcohol glucosides based on the Fe(III)-promoted oxidative coupling has been achieved. Obtained common intermediates were further selectively modified to yield the basic molecular core possessing three orthogonally protected alkoxy functionalities available for further selective modifications. Graphical abstract: [Figure not available: see fulltext.].
- Barbuková, Zuzana,Kozubíková, Hana,Zále?ák, Franti?ek,Dole?al, Karel,Pospí?il, Ji?í
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p. 737 - 748
(2018/01/01)
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- Bioinspired Diastereoconvergent Synthesis of the Tricyclic Core of Palodesangrens via Diels-Alder Reaction, LiAlH4-Mediated Isomerization, and Acid-Mediated Cyclization
-
The cyclohexene moiety of the tricyclic 6,7-diaryl-tetrahydro-6H-benzo[c]chromene core of palodesangrens could be assembled in a biomimetic and step-economical fashion by the Diels-Alder reaction between the electron-rich (E)-1,3-butadienylarenes as the diene and the electron-deficient chalcones as the dienophile. During the reduction of ketone to the corresponding alcohol by LiAlH4, the mixture of endo and exo isomers underwent a novel diastereoconvergent LiAlH4-mediated isomerization to install the desired stereochemistry at C10a. Subsequent pyran ring closure under acidic conditions installed the stereochemistry at the remaining C6. Overall, the tricyclic core of palodesangrens could be prepared in three steps and up to 38% yield.
- Songthammawat, Poramate,Wangngae, Sirilak,Matsumoto, Koki,Duangkamol, Chuthamat,Ruchirawat, Somsak,Ploypradith, Poonsakdi
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p. 5225 - 5241
(2018/05/07)
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- A rapid, solvent-free deprotection of methoxymethyl (MOM) ethers by pTSA; An eco-friendly approach
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Background: Ease of preparation and alkaline stability of methoxymethyl (MOM) makes it an important hydroxyl protecting group. A number of methods are available for the deprotection of MOM. Though the methods are good in general, they use solvents, require prolonged reaction time and tedious work up. A solvent free, solid phase, fast deprotection of MOM has been developed and is the major theme of this paper. Methods: A mixture of MOM protected compounds and pTSA is triturated in a mortar (5 min) and left at room temperature for 30 min. On addition of water (4°C), pTSA, methanol and formaldehyde dissolved leaving the products as precipitates. Results: A series of different MOM ethers were deprotected by this method in good to excellent yield (85-98%). The compatibility of MOM in the presence of other protections such as methoxyl, benzyl, ester, amide, allyl and lactone was also established. Acetate protection is not stable under these conditions. Conclusion: An efficient, selective and high yielding deprotection MOM groups by pTSA under solvent free condition is described. The process is environment friendly since no solvent was used in the deprotection process. The reaction conditions are mild and should be useful for the deprotection of MOM derivatives of complex and labile molecules.
- Pandurangan, Nanjan
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p. 231 - 235
(2017/07/15)
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- Bismuth trichloride–mediated cleavage of phenolic methoxymethyl ethers
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A simple and efficient method for removal of phenolic methoxymethyl ethers in the presence of 30?mol% of bismuth trichloride in acetonitrile/water is described. Notable features of the cleavage protocol entail use of an ecofriendly bismuth reagent, ease of handling, low cost, operational simplicity, and good functional group compatibility. A number of structurally varied phenolic methoxymethyl ethers were cleaved in good to excellent yields.
- Obaro-Best, Oghale,Reed, Jack,Norfadilah, Alya A. F. B.,Monahan, Ryan,Sunasee, Rajesh
-
supporting information
p. 586 - 593
(2016/06/08)
-
- Synthesis of Two Natural Furan-Cyclized Diarylheptanoids via 2-Furaldehyde
-
Two natural diarylheptanoids, 2-benzyl-5-(2-phenylethyl)furan (1) and 2-methoxy-4-{[5-(2-phenylethyl)furan-2-yl]methyl}phenol (2), were synthesized starting from 2-furaldehyde. A Wittig reaction of 2-furaldehyde with benzyltriphenylphosphonium bromide followed by reduction of the alkene C=C bond with Mg gave 2-(2-phenylethyl)furan (5). Lithiation of 5 with BuLi at -78 followed by alkylation with benzyl bromide gave natural product 1. In another approach, Friedel-Crafts acylation of compound 5 with benzoyl chloride followed by deoxygenation of the C=O group afforded 1. The natural product 2 was also synthesized by acylation of 5 with 4-acetoxy-3-methoxybenzoyl chloride (16) followed by deoxygenation and deacetylation.
- Se?inti, Hatice,Se?en, Hasan
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p. 938 - 944
(2015/11/23)
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- Synthesis of non-prenyl analogues of baccharin as selective and potent inhibitors for aldo-keto reductase 1C3
-
Inhibitors of a human member (AKR1C3) of the aldo-keto reductase superfamily are regarded as promising therapeutics for the treatment of prostatic and breast cancers. Baccharin [3-prenyl-4-(dihydrocinnamoyloxy)cinnamic acid], a component of propolis, was shown to be both potent (Ki56 nM) and highly isoform-selective inhibitor of AKR1C3. In this study, a series of derivatives of baccharin were synthesized by replacing the 3-prenyl moiety with aryl and alkyl ether moieties, and their inhibitory activities for the enzyme were evaluated. Among them, two benzyl ether derivatives, 6m and 6n, showed an equivalent inhibitory potency to baccharin. The molecular docking of 6m in AKR1C3 has allowed the design and synthesis of (E)-3-{3-[(3-hydroxybenzyl)oxy]-4-[(3-phenylpropanoyl)oxy]phenyl}acrylic acid (14) with improved potency (Ki6.4 nM) and selectivity comparable to baccharin. Additionally, 14 significantly decreased the cellular metabolism of androsterone and cytotoxic 4-oxo-2-nonenal by AKR1C3 at much lower concentrations than baccharin.
- Endo, Satoshi,Hu, Dawei,Matsunaga, Toshiyuki,Otsuji, Yoko,El-Kabbani, Ossama,Kandeel, Mahmoud,Ikari, Akira,Hara, Akira,Kitade, Yukio,Toyooka, Naoki
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p. 5220 - 5233
(2014/12/10)
-
- Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands
-
The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.
- Kim, Myeong Seop,Ki, Yooran,Ahn, Song Yeon,Yoon, Suyoung,Kim, Sung-Eun,Park, Hyeung-Geun,Sun, Wei,Son, Karam,Cui, Minghua,Choi, Sun,Pearce, Larry V.,Esch, Timothy E.,Deandrea-Lazarus, Ian A.,Blumberg, Peter M.,Lee, Jeewoo
-
p. 382 - 385
(2014/01/17)
-
- Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands
-
The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.
- Kim, Myeong Seop,Ki, Yooran,Ahn, Song Yeon,Yoon, Suyoung,Kim, Sung-Eun,Park, Hyeung-Geun,Sun, Wei,Son, Karam,Cui, Minghua,Choi, Sun,Pearce, Larry V.,Esch, Timothy E.,Deandrea-Lazarus, Ian A.,Blumberg, Peter M.,Lee, Jeewoo
-
p. 382 - 385
(2015/08/19)
-
- Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands
-
The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.
- Kim, Myeong Seop,Ki, Yooran,Ahn, Song Yeon,Yoon, Suyoung,Kim, Sung-Eun,Park, Hyeung-Geun,Lee, Jeewoo,Sun, Wei,Son, Karam,Cui, Minghua,Choi, Sun,Pearce, Larry V.,Esch, Timothy E.,DeAndrea-Lazarus, Ian A.,Blumberg, Peter M.
-
p. 382 - 385
(2015/03/18)
-
- Synthesis of natural and non-natural curcuminoids and their neuroprotective activity against glutamate-induced oxidative stress in HT-22 cells
-
A strategy for the synthesis of natural and non-natural 5-deoxy-6,7-dihydrocurcuminoids (diarylheptanoids) was developed for the preparation of 14 compounds with varying aromatic substituent patterns and a different functionality in the aliphatic seven-carbon chain. The in vitro protective activity against glutamate-induced neuronal cell death was examined in the murine hippocampal cell line HT-22 to find structural motifs responsible for neuroprotective effects in vitro. Among the tested compounds the ferulic acid-like unit, present in the structures of (E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-1-en-3-one (5) and (E)-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hept-1-en-3-one (7), appeared to be an important feature for protection against glutamate-induced neurotoxicity. Both compounds demonstrated significant neuroprotective activity in a concentration range between 1 and 25 ~M without showing toxic effects in a cytotoxicity assay with HT-22 cells. Furthermore, (E)-1,7-bis(3,4-dihydroxyphenyl)hept-1-en-3-one (9), exhibiting a caffeic acid-like structural motif, displayed a neuroprotective activity at a nontoxic concentration of 25 ~M. In contrast, (1E,6E)-1,7-bis(3,4-dihydroxyphenyl)hepta-1,6-diene-3,5-dione (4, di-O-demethylcurcumin) showed mainly cytotoxic effects. A corresponding single-ring analogue that contains the ferulic acid-like unit as an enone was not active.
- Jirsek, Petr,Amslinger, Sabine,Heilmann, J?rg
-
p. 2206 - 2217
(2014/12/11)
-
- Total synthesis of cannabisin F
-
A practical eight-step synthesis of lignanamide cannabisin F starting from vanillin is reported for the first time. This synthetic strategy applies the aldol reaction followed by the Wittig reaction to afford the key 8-O-4′-neolignan intermediate diacid. The diacid was condensed with N,O-protected tyramine giving, after deprotection, cannabisin F.
- Xia, Ya-Mu,Xia, Jun,Chai, Chen
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p. 384 - 391
(2014/01/06)
-
- Enantioselective synthesis of orthogonally protected (2R,3R)-(-)- epicatechin derivatives, key intermediates in the de novo chemical synthesis of (-)-epicatechin glucuronides and sulfates
-
Ten orthogonally protected (-)-epicatechin and 3′- or 4′-O-methyl-(-)-epicatechin derivatives were prepared in a regiospecific and enantioselective manner. For each orthogonally protected (-)-epicatechin derivative, one specific phenolic hydroxyl was protected with a methoxymethyl (MOM) or p-methoxybenyzl (PMB) group and the remainder were protected as benzyl ethers. These uniquely protected (-)-epicatechin derivatives were designed to facilitate the regiospecific installation of a glucuronic acid or sulfate unit onto (-)-epicatechin after selective removal of the MOM or PMB protecting group to provide authentic standards of (-)-epicatechin glucuronides and sulfates.
- Zhang, Mingbao,Erik Jagdmann Jr.,Van Zandt, Michael,Beckett, Paul,Schroeter, Hagen
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p. 362 - 373
(2013/06/27)
-
- Small molecules that protect against β-amyloid-induced cytotoxicity by inhibiting aggregation of β-amyloid
-
Aggregated β-amyloid (Aβ) plays crucial roles in Alzheimer's disease (AD) pathogenesis, therefore blockade of Aβ aggregation is considered as a potential therapeutic target. We designed and synthesized small molecules to reduce Aβ-induced cytotoxicity by inhibiting Aβ aggregation. The small molecules were screened via ThT, MTT, and cell-based cytotoxicity assay (Aβ burden assay). Selected compounds 1c, 1d, 1e, and 1f were then investigated by evaluating their effects on cognitive impairment of acute AD mice model. Learning and memory dysfunction by injection of Aβ(1-42) was recovered by administration of these molecules. Especially, 1d showed the best recovery activity in Y-maze task, object recognition task, and passive avoidance task with dose dependent manner. These results suggest that 1d has high potential as a therapeutic agent for AD.
- Lee, Yun Suk,Kim, Hye Yun,Kim, Youngsoo,Seo, Jae Hong,Roh, Eun Joo,Han, Hogyu,Shin, Kye Jung
-
experimental part
p. 4921 - 4935
(2012/10/08)
-
- Synthesis and antioxidant capacities of hydroxyl derivatives of cinnamoylphenethylamine in protecting DNA and scavenging radicals
-
Cinnamoylphenethylamine (CNPA) derivatives including feruloylphenethylamine (FRPA), caffeoylphenethylamine (CFPA), cinnamoyltyramine (CNTA), feruloyltyramine (FRTA) and caffeoyltyramine (CFTA) were synthesized in order to investigate the influence of the number and position of hydroxyl group on Cu2+/glutathione (GSH) and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. The radical-scavenging properties of these CNPA derivatives were also evaluated by trapping 2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonate) cationic radical (ABTS), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) and galvinoxyl radical. In addition, these CNPA derivatives were tested by linoleic acid (LH)-β-carotene-bleaching experiment. The chemical kinetic was employed to treat the results from AAPH-induced oxidation of DNA and gave the order of antioxidant ability as CFTA > CFPA > FRTA > FRPA. CFTA and CFPA also possessed high abilities to inhibit Cu2+/GSH-mediated degradation of DNA, whereas FRPA and FRTA can protect LH against the auto-oxidation efficiently. Finally, CFPA and FRPA exhibited high activity in trapping ABTS, DPPH and galvinoxyl radicals. Therefore, the cinnamoyl group bearing ortho-dihydroxyl or hydroxyl with ortho-methoxyl benefited for CNPA derivatives to protect DNA, while hydroxyl in tyramine cannot enhance the radical-scavenging abilities of CNPA derivatives.
- Yang, Yang,Song, Zhi-Guang,Liu, Zai-Qun
-
experimental part
p. 445 - 453
(2012/05/20)
-
- Asymmetric synthesis of erythro-8-O-4'-neolignan Machilin C
-
A new methodology for the synthesis of the erythro-8-O-4'-neolignan Machilin C based on the Sharpless asymmetric dihydroxylation reaction and the Mitsunobu reaction as two key steps is described.
- Xia, Yamu,Chang, Liang,Ding, Yining,Jiao, Bin
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scheme or table
p. 151 - 152
(2011/07/08)
-
- Asymmetric synthesis of machilin C and its analogue
-
Full details of the asymmetric total synthesis of erythro-8-O-4′-neolignan, machilin C, and its analogue perseal A are reported. The synthesis was involved in the Sharpless dihydroxylation reaction that occurred with excellent asymmetric induction, and the Mitsunobu reaction which occurred with inversion of the absolute configuration from the threo to the erythro isomer. The synthesis was achieved from simple vanillin in eight to twelve steps.
- Xia, Yamu,Wang, Wei
-
experimental part
p. 630 - 636
(2011/10/19)
-
- PYRAZOLONE DERIVATIVE AND PDE INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
-
It is to provide a novel pyrazolone derivative represented by the following general formula (1), which is useful as a pharmaceutical and has a phosphodiesterase inhibitory action: wherein R1,R2: C1-6 alkyl; R3,R4: H, X, C1-6 alkoxy; Z:O, S; A:AA, BB, wherein AA represents wherein BB represents wherein R5: H, C1-6 alkyl ; R6,R7: C1-6 alkyl.
- -
-
Page/Page column 145-146
(2010/04/25)
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- Factors affecting orthogonality in the deprotection of 2,4-di-protected aromatic ethers employing solid-supported acids
-
Selective deprotection of aromatic ethers bearing two protecting groups on the same aromatic ring by solid-supported acids (Amberlyst-15 and PTS-Si) was systematically investigated. ortho-Directing protonation by the carbonyl group as well as carbocation stability and quenching are the important determining factors for the orthogonal deprotection process. Stablilized carbocations (e.g., those from the MOM and PMB groups) could be removed with high selectivity.
- Tangdenpaisal, Kassrin,Sualek, Supannee,Ruchirawat, Somsak,Ploypradith, Poonsakdi
-
experimental part
p. 4316 - 4325
(2009/10/17)
-
- Synthesis of riccardin C and its seven analogues. Part 1: The role of their phenolic hydroxy groups as LXRα agonists
-
Riccardin C, a nuclear receptor LXRα selective agonist, is an 18-membered macrocyclic bisbibenzyl isolated from several liverworts. Synthesis of riccardin C and its seven O-methylated derivatives was accomplished. The synthetic sequence highlights an intramolecular Suzuki-Miyaura coupling in the formation of the 18-membered biaryl linkage present in riccardin C. The structure-activity relationship of these compounds suggests that all of the phenolic hydroxy groups present in riccardin C are essential for the activation of LXRα.
- Hioki, Hideaki,Shima, Naoki,Kawaguchi, Kota,Harada, Kenich,Kubo, Miwa,Esumi, Tomoyuki,Nishimaki-Mogami, Tomoko,Sawada, Jun-ichi,Hashimoto, Toshihiro,Asakawa, Yoshinori,Fukuyama, Yoshiyasu
-
scheme or table
p. 738 - 741
(2009/12/03)
-
- Halogenation of 4-hydroxy-3-methoxybenzyl thiourea TRPV1 agonists showed enhanced antagonism to capsaicin
-
Selected potent TRPV1 agonists (1-6) have been modified by 5- or 6-halogenation on the aromatic A-region to analyze their effects on potency and efficacy (agonism versus antagonism). The halogenation caused enhanced functional antagonism at TRPV1 compared to the corresponding prototype agonists. The analysis of SAR indicated that the antagonism was enhanced as the size of the halogen increased (I > Br > Cl) and when the 6-position was halogenated. Compounds 23c and 31b were found to be potent full antagonists with Ki (as functional antagonist) = 23.1 and 30.3 nM in rTRPV1/CHO system, respectively.
- Kang, Dong Wook,Ryu, HyungChul,Lee, Jeewoo,Lang, Krystle A.,Pavlyukovets, Vladimir A.,Pearce, Larry V.,Ikeda, Tetsurou,Lazar, Jozsef,Blumberg, Peter M.
-
p. 214 - 219
(2007/10/03)
-
- Substituted trans-stilbenes, including analogues of the natural product resveratrol, inhibit the human tumor necrosis factor alpha-induced activation of transcription factor nuclear factor kappaB
-
The transcription factor nuclear factor kappaB (NF-κB), which regulates expression of numerous antiinflammatory genes as well as genes that promote development of the prosurvival, antiapoptotic state is up-regulated in many cancer cells. The natural product resveratrol, a polyphenolic trans-stilbene, has numerous biological activities and is a known inhibitor of activation of NF-κB, which may account for some of its biological activities. Resveratrol exhibits activity against a wide variety of cancer cells and has demonstrated activity as a cancer chemopreventive against all stages, i.e., initiation, promotion, and progression. The biological activities of resveratrol are often ascribed to its antioxidant activity. Both antioxidant activity and biological activities of analogues of resveratrol depend upon the number and location of the hydroxy groups. In the present study, phenolic analogues of resveratrol and a series of substituted trans-stilbenes without hydroxy groups were compared with resveratrol for their abilities to inhibit the human tumor necrosis factor alpha-induced (TNF-α) activation of NF-κB, using the Panomics NF-κB stable reporter cell line 293/NF-κB-luc. A series of 75 compounds was screened to identify substituted trans-stilbenes that were more active than resveratrol. Dose-response studies of the most active compounds were carried out to obtain IC50 values. Numerous compounds were identified that were more active than resveratrol, including compounds that were devoid of hydroxy groups and were 100-fold more potent than resveratrol. The substituted trans-stilbenes that were potent inhibitors of the activation of NFκB generally did not exhibit antioxidant activity. The results from screening were confirmed using BV-2 microglial cells where resveratrol and analogues were shown to inhibit LPS-induced COX-2 expression.
- Heynekamp, Justin J.,Weber, Waylon M.,Hunsaker, Lucy A.,Gonzales, Amanda M.,Orlando, Robert A.,Deck, Lorraine M.,Vander Jagt, David L.
-
p. 7182 - 7189
(2007/10/03)
-
- 3-PHENYL-N- ((1, 3, 4) THIADIAZOL-2-YL) -ACRYLAMIDE DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF ESTROGEN-RELATED RECEPTORS FOR THE TREATMENT OF E.G. CANCER, RHEUMATOID ARTHRITIS OR NEUROLOGICAL DISORDERS
-
Compounds of formula (I) are provided as well as compositions and methods of using compounds of formula (I) for modulating the activity of the estrogen-related receptors and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder related to the activity of the estrogen-related receptor. Considering the wide range of activity of the nuclear hormone receptor ERRα, the compounds described herein which are capable of modulating ERRα activity, are useful for treating a range of disease states including cancer, diabetes, obesity, hyperlipidermia, arthritis, atherosclerosis, osteoporosis, anxiety, depression, Parkinson’s disease and Alzheimer’s disease. Formula (I). The substituents are defined in the claims.
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-
Page/Page column 53
(2010/02/13)
-
- Synthesis of deuterium labeled silybin and isosilybin
-
A simple synthesis of the deuterium labeled (+)-silybin [(+)-1c,d], (+)-isosilybin [(+)-2c,d] and their 1,4-benzodioxane building block [rac.-1f] have been achieved in seven steps starting from vanilline (5).
- Ferenczi, Renata,Kurtan, Tibor,Dinya, Zoltan,Antus, Sandor
-
p. 491 - 494
(2007/10/03)
-
- Studies on flavans. III. The total synthesis of (±)-7,4′ -dihydroxy-3′-methoxyflavan, (±)-7,3′-dihydroxy-4′ -methoxyflavan, and (±)-7,4′-dihdroxyflavan
-
The first total synthesis of (±)-7,3′-dihydroxy-4′ -methoxyflavan (1) and (±)-7,4′-dihydroxy-3′-methoxyflavan (2), along with the synthesis of (±)-7,4′-dihydroxyflavan (3), three naturally occurring flavans, were described. The key step is the cyclization of 1,3-diaryl-1-propanol by BF3·Et2O.
- Xue, Jijun,Zhang, Xianshu,Chen, Xuesong,Zhang, Yingpeng,Li, Ying
-
p. 3527 - 3536
(2007/10/03)
-
- Synthesis and 11c-labelling of (E,E)-1-(3′,4′-dihydroxystyryl)-4-(3′-methoxy-4 ′-hydroxystyryl) benzene for PET imaging of amyloid deposits
-
Carboxylic acid derivatives of the amyloid-binding dye Congo red do not enter the brain well and are thus unable to serve as in vivo amyloid-imaging agents. A neutral amyloid probe, (E,E)-1-(3′,4′-dihydroxystyryl)-4-(3′-methoxy-4 ′-hydroxystyryl)benzene (3), devoid of any carboxylate groups has been designed and synthesized via a 12-step reaction sequence with a total yield of 30%. The unsymmetric compound 3 has also been labelled with C-11 via [11C]methyl iodide ([11C]CH3I) methylation of a symmetric 4,4′-dimesyl protected precursor followed by deprotection. Preliminary evaluation indicated that compound 3 selectively stained plaques and neurofibrillary tangles in post-mortem AD brain, and exhibited good binding affinity (Ki = 38 ± 8 nM) for Aβ(1-40) fibrils in vitro. In vivo pharmacokinetic studies indicated that [11C]3 exhibited higher brain uptake than its carboxylic acid analogs and good clearance from normal control mouse brain. [11C]3 also exhibited specific in vivo binding to pancreatic amyloid deposits in the NOR-beta transgenic mouse model. These results justify further investigation of 3 and similar derivatives as surrogate markers for in vivo quantitation of amyloid deposits. Copyright
- Wang, Yanming,Mathis, Chester A.,Huang, Guo-Feng,Holt, Daniel P.,Debnath, Manik L.,Klunk, William E.
-
p. 647 - 664
(2007/10/03)
-
- Vanilloid and isovanilloid analogues as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases
-
As aminoacyl adenylate surrogates, a series of methionyl and isoleucyl phenolic analogues containing bioisosteric linkers mimicking ribose have been investigated. Inhibition of synthesized compounds to the aminoacylation reaction by the corresponding Escherichia coli methionyl-tRNA and isoleucyl-tRNA synthetases indicated that 18 was found to be a potent inhibitor of isoleucyl-tRNA synthetase. A molecular modeling study demonstrated that in 18, isovanillate and hydroxamate served as proper surrogates for adenine and ribose in isoleucyl adenylate, respectively.
- Lee, Jeewoo,Kang, Sang Uk,Kim, Su Yeon,Kim, Sung Eun,Jo, Yeong Joon,Kim, Sunghoon
-
p. 965 - 968
(2007/10/03)
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- An expeditious synthesis of vibsanol, a benzofuran-type lignan from Viburnum awabuki
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Vibsanol (1), a benzofuran-type lignan isolated from the wood of Viburnum awabuki (Caprifoliaceae), was synthesized from the readily available vanillin; the key step is a tandem cyclization of o-tert- butyldimethylsiloxydiarylalkyne (2) with tetrabutylammonium fluoride and excess paraformaldehyde.
- Sakai, Atsushi,Aoyama, Toyohiko,Shioiri, Takayuki
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p. 643 - 659
(2007/10/03)
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- New syntheses of the benzoquinone primin and its water-soluble analog primin acid via Heck reactions
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The syntheses of primin, 2-methoxy-6-pentylbenzoquinone (1), a major allergen of Primula obconica, and its water-soluble acid analog primin acid (2) are reported. The key steps were ortho-lithiation reactions of protected hydroquinones, palladium coupling (Heck) reactions, and salcomine-catalyzed oxidations of phenols to quinones.
- Mabic,Vaysse,Benezra,Lepoittevin
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p. 1127 - 1134
(2007/10/03)
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- Phenol compound having antioxidative activity and the process for preparing the same
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Disclosed are a phenol compound represented by the formula (1): STR1 wherein R0 represents H, alkyl or alkyloxy; R1 represents alkyl; R2 represents alkyl or alkyloxy; OR3 represents OH; R4 represents H, lower alkyl or acyl, each of the above substituents may be substituted; W represents O, S or NR7 ; where R7 represents H, alkyl, aryl, OH or alkyloxy, a group of the formula (2): STR2 represents an amino which may be mono- or di-substituted or heterocyclic group containing N atom, or a pharmaceutically acceptable salt thereof, and a process for preparing the same.
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- Facile one-pot transformation of 2,3-epoxy alcohols into allylic alcohols: First total synthesis of (-)-4-O-(6'-hydroxy- 7'(9')-dehydro- 6',7'-dihydrogeranyl)coniferol
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An efficient and practical synthesis of optically active allylic alcohols from 2,3-epoxy alcohols by the in situ formation of the epoxy iodides and their subsequent reduction with phosphine hydroxyiodide has been established. Using this reaction as the key step, we synthesized (-)-4-O- (6'-hydroxy-7'(9')-dehydro-6',7'-dihydrogeranyl)coniferol.
- Liu, Zuosheng,Lan, Jiong,Li, Yulin
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p. 3755 - 3762
(2007/10/03)
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- ANTI-OXIDATIVE AND ANTI-INFLAMMATORY CURCUMIN-RELATED PHENOLICS FROM RHIZOMES OF CURCUMA DOMESTICA
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Two new natural phenolics were isolated from the rhizomes of Curcuma domestica along with four known curcuminoids.The structures of the former were determined to be 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-(1E,4E)-1,4-dien-3-one and 1-(4-hydroxy-3-methoxyphenyl)-5-(4-hydroxyphenyl)-penta-(1E,4E)-1,4-dien-3-one, respectively, by spectral data and syntheses.Anti-oxidant activity of the phenolics was determined by the inhibition of autoxidation of linoleic acid in a water-alcohol system.Anti-inflammatory activity of the isolated compounds was determined on mouse ears by using a tumour promoter, TPA (12-O-tetradecanoylphorbol-13-acetate) as an inducer. Key Word Index: Curcuma domestica; Zingiberaceae; rhizome; curcuminoid; phenolic; anti-inflammatory activity; antioxidant activity.
- Masuda, Toshiya,Jitoe, Akiko,Isobe, Junko,Nakatani, Nobuji,Yonemori, Sigetomo
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p. 1557 - 1560
(2007/10/02)
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- Anti-ulcer agent comprising chalcone derivative as effective ingredient and novel chalcone derivative
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The present invention relates to an anti-ulcer agent comprising a compound represented by the following general formula I as the effective ingredient, and a novel chalcone derivative included in the compound represented by this general formula I: STR1 wherein X and Y independently stand for a hydrogen atom or together form a single bond, R1 stands for a hydroxyl group, an acetoxy group, a carboxymethoxy group or a methoxycarbonylmethoxy group, R2 stands for a hydrogen atom, an isoprenyl group, isopentyl group or a propyl group, R3 stands for hydroxyl group or a methoxy group, R4 stands for a hydrogen atom, a hydroxyl group or a methoxy group, R5 stands for a hydrogen atom, a hydroxyl group, a methoxy group or an isopentyl group, R6 stands for a hydroxyl group, a methoxy group or a carboxymethoxy group, and R7 stands for a hydrogen atom or a methoxy group.
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- A Convenient Synthesis of Homobutein
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Homobutein (4) has been synthesised by the condensation of 2-hydroxy-4-(methoxymethoxy)acetophenone (1) and 3-methoxy-4-(methoxymethoxy)benzaldehyde (2) followed by demethoxymethylation of the resulting chalcone (3).
- Begum, S. Dilshad,Parthasarathi, J.
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- An Improved Synthesis of 1,4-Benzo- and 1,4-Naphthoquinones Bearing Active Substituents
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The synthesis of 1,4-benzoquinones and 1,4-naphthoquinones 3a-j carrying substituents such as methoxyl, allyl or oxiranyl was substantially improved.The 1-methoxy-4-methoxymethyloxy 2a-d, g-k or 1,4-bis(methoxymethyloxy) derivatives 2e-f were used, as a substrates instead of 1,4-dimethoxy derivatives 1a-j hitherto used and they were oxidized with silver(II) dipicolinate.Among numerous examples, the synthesis of a new analog of ubiquinone 3d with the oxiranyl substituent, being a new bioactivated alkylating agent, is reported.
- Syper, Ludwik,Kloc, Krystian,Mlochowski, Jacek
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p. 808 - 822
(2007/10/02)
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