- In vitro study and structure-activity relationship analysis of stilbenoid derivatives as powerful vasorelaxants: Discovery of new lead compound
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The development of vasorelaxant as the antihypertensive drug is important as it produces a rapid and direct relaxation effect on the blood vessel muscles. Resveratrol (RV), as the most widely studied stilbenoid and the lead compound, inducing the excellent vasorelaxation effect through the multiple signalling pathways. In this study, the in vitro vascular response of the synthesized trans-stilbenoid derivatives, SB 1-8e were primarily evaluated by employing the phenylephrine (PE)-precontracted endothelium-intact isolated aortic rings. Herein we report trans-3,4,4′-trihydroxystilbene (SB 8b) exhibited surprisingly more than 2-fold improvement to the maximal relaxation (Rmax) of RV. This article also highlights the characterization of the aromatic protons in terms of their unique splitting patterns in 1H NMR.
- Chan, Sock Ying,Loh, Yean Chun,Oo, Chuan Wei,Yam, Mun Fei
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- Development of Tetrachlorophthalimides as Liver X Receptor β (LXRβ)-Selective Agonists
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Liver X receptor (LXR) agonists are candidates for the treatment of atherosclerosis via induction of ABCA1 (ATP-binding cassette A1) gene expression, which contributes to reverse cholesterol transport (RCT) and to cholesterol efflux from the liver and intestine. However, LXR agonists also induce genes involved in lipogenesis, such as SREBP-1c (sterol regulatory binding element protein 1c) and FAS (fatty acid synthase), thereby causing an undesirable increase in plasma and hepatic triglyceride (TG) levels. Recent studies indicate that LXRα contributes to lipogenesis in liver, and selective LXRβ activation improves RCT in mice. Therefore, LXRβ-selective agonists are promising candidates to improve atherosclerosis without increasing plasma or hepatic TG levels. However, the ligand-binding domains in the two LXR isoforms α/β share high sequence identity, and few LXR ligands show subtype selectivity. In this study we identified a tetrachlorophthalimide analogue as an LXRβ-selective agonist. Structural development led to (E)-4,5,6,7-tetrachloro-2-(2-styrylphenyl)isoindoline-1,3-dione (24 a), which shows potent and selective LXRβ agonistic activity in reporter gene assays. In binding assays, compound 24 a bound to LXRβ preferentially over LXRα. It also induced the expression of ABCA1 mRNA but not SREBP-1c mRNA in cells. Compound 24 a appears to be a promising lead compound for therapeutic agents to treat atherosclerosis without the side effects induced by LXRα/β dual agonists.
- Nomura, Sayaka,Endo-Umeda, Kaori,Makishima, Makoto,Hashimoto, Yuichi,Ishikawa, Minoru
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p. 2347 - 2360
(2016/10/25)
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- Well-defined cyclopropenone-masked dibenzocyclooctyne functionalized polymers from atom transfer radical polymerization
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Two functional atom transfer radical polymerization (ATRP) initiators (I-2 and I-3) were developed bearing a cyclopropenone-masked dibenzocyclooctyne group. ATRP was then explored on three main kinds of monomers for radical polymerization including acryla
- Sun, Peng,Yan, Guowei,Tang, Qingquan,Chen, Yongming,Zhang, Ke
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p. 202 - 209
(2015/05/05)
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- Styrylphenylphthalimides as Novel Transrepression-Selective Liver X Receptor (LXR) Modulators
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Anti-inflammatory effects of liver X receptor (LXR) ligands are thought to be largely due to LXR-mediated transrepression, whereas side effects are caused by activation of LXR-responsive gene expression (transactivation). Therefore, selective LXR modulators that preferentially exhibit transrepression activity should exhibit anti-inflammatory properties with fewer side effects. Here, we synthesized a series of styrylphenylphthalimide analogues and evaluated their structure-activity relationships focusing on LXRs-transactivating-agonistic/antagonistic activities and transrepressional activity. Among the compounds examined, 17l showed potent LXR-transrepressional activity with high selectivity over transactivating activity and did not show characteristic side effects of LXR-transactivating agonists in cells. This representative compound, 17l, was confirmed to have LXR-dependent transrepressional activity and to bind directly to LXRβ. Compound 17l should be useful not only as a chemical tool for studying the biological functions of LXRs transrepression but also as a candidate for a safer agent to treat inflammatory diseases.
- Nomura, Sayaka,Endo-Umeda, Kaori,Aoyama, Atsushi,Makishima, Makoto,Hashimoto, Yuichi,Ishikawa, Minoru
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supporting information
p. 902 - 907
(2015/08/24)
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- SAR study on arylmethyloxyphenyl scaffold: Looking for a P-gp nanomolar affinity
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Starting from the previously developed P-gp ligands 1a and 1b (EC 50 = 0.25 μM and 0.65 μM, respectively), new arylmethyloxyphenyl derivatives have been synthesized as P-gp modulators in order to investigate: (i) the effect of small electron-do
- Nesi, Giulia,Colabufo, Nicola Antonio,Contino, Marialessandra,Perrone, Maria Grazia,Digiacomo, Maria,Perrone, Roberto,Lapucci, Annalina,Macchia, Marco,Rapposelli, Simona
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p. 558 - 566
(2014/04/03)
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- Oxidative cyclizations, the synthesis of aryl-substituted c-glycosides, and the role of the second electron transfer step
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Anodic oxidation reactions have been used to synthesize aryl- and biaryl-substituted C-glycosides. The reactions take advantage of the tendency for alcohol nucleophiles to trap nonpolar radical cations. The addition of the alcohol to the radical cation appears to be reversible, and the success of the cyclizations is dependent on the ease with which the resulting benzylic radical is oxidized.
- Smith, Jake A.,Moeller, Kevin D.
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supporting information
p. 5818 - 5821
(2013/12/04)
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- Synthesis and structure of styryl-substituted azines
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New photochromic derivatives of 2-styrylquinoline and 2-styrylquinoxaline were obtained by the condensation of the methyl derivatives of the mentioned heterocycles with substituted benzaldehydes in the presence of basic and acidic catalysts, and also unde
- Gulakova,Sitin,Kuz'Mina,Fedorova
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experimental part
p. 245 - 252
(2011/05/03)
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- 1-PHENYLALCOXY-2-BETA-PHENYLETHYL DERIVATIVES AS P-GLYCOPROTEIN (P-GP) INHIBITORS USEFUL IN DRUG RESISTANCE EVENTS
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The invention relates to a new class of compounds, which are 1-phenylalcoxy-2-β-phenylethyl derivatives, as P-glycoprotein (P-GP) inhibitors. These compounds are useful in drug resistance events. They have been shown able to inhibit in a dose-dependent ma
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Page/Page column 10
(2009/04/24)
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- Synthesis and biological evaluation of (hetero)arylmethyloxy- and arylmethylamine-phenyl derivatives as potent P-glycoprotein modulating agents
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Starting from lead compounds 12b and 28b, previously characterized as P-glycoprotein (P-gp) modulating agents, two series of new compounds were investigated. Compounds 14a,b and 15a,b displayed high P-gp modulating activity in the submicromolar range (EC
- Colabufo, Nicola Antonio,Berardi, Francesco,Perrone, Roberto,Rapposelli, Simona,Digiacomo, Maria,Vanni, Michael,Balsamo, Aldo
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p. 1415 - 1422
(2008/09/21)
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- Arylmethyloxyphenyl derivatives: Small molecules displaying P-glycoprotein inhibition
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Some arylmethyloxyphenyl derivatives were prepared as simplified structures of analogous arylpiperazines with high affinity toward dopaminergic D 2 and serotonergic 5-HT1A receptors and inhibiting P-glycoprotein (P-gp). The compounds 5b and 8b displayed good P-gp inhibition activity measured as [3H]vinblastine transport inhibition in the Caco-2 cell monolayer and intracellular doxorubicin accumulation in MCF7/Adr cells by flow cytometry. Compounds 5b and 8b also inhibited, dose-dependently, ATP-ase activation induced by P-gp substrate vinblastine.
- Colabufo, Nicola Antonio,Berardi, Francesco,Perrone, Roberto,Rapposelli, Simona,Digiacomo, Maria,Balsamo, Aldo
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p. 6607 - 6613
(2007/10/03)
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- First total synthesis of an analogue of montbretyl 12-methyl ether
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The first total synthesis of the title compound 1 was accomplished starting from α-cyclocitral and benzyl triphenylphosphonium chloride 3 in seven steps via a strategy of AC→ABC. In the synthesis, t-BuOK/t-BuOH system was utilised for enolisation and the iso-propyl group was introduced in the last step.
- Zhang, Cheng-Lu,Qiu, Ye-Hong,Pan, Xin-Fu
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p. 232 - 233
(2007/10/03)
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- Novel cyclic amide derivatives
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Novel compounds represented by the following formula (I) that act as a ligand to sigma receptor/binding cite and a medicament comprising the same as an active ingredient: wherein X represents an alkyl group, an aryl group, a heterocyclic group or the like; Q represents a group represented by —CH2—, —CO—, —O—, —CH(OR7)— or the like wherein R7 represents a hydrogen atom, an alkyl group or the like; n represents an integer of from 0 to 5; R1 and R2 each represent a hydrogen atom, an alkyl group or the like; B represents either of the following groups: wherein R3, R4, R5, and R6 each represent a hydrogen atom, a halogen atom, an alkoxyl group or the like; m represents 1 or 2; and the ring of: represents an aromatic heterocyclic ring.
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- 1-(2,6-Dichloro-4-hydroxyphenyl)-2-phenylethanes - New biological response modifiers for the therapy of breast cancer. Synthesis and evaluation of estrogenic/antiestrogenic properties
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[meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) complexes (meso-1-ptll′; L,l′= Cl orL = H2O and L′ = OSO3) are highly effective towards hormone-sensitive, rodent breast cancers due to their significant estroge
- Schertl, Sabine,Hartmann, Rolf W.,Batzl-Hartmann, Christine,Schlemmer, Richard,Spru, Thilo,Bernhardt, Guenther,Gust, Ronald,Schoenenberger, Helmut
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p. 125 - 137
(2007/10/03)
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- Third generation antitumor platinum(II) complexes of the [1-(fluoro/difluorophenyl)-2-phenylethylenediamine]platinum(II) type
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The diastereomeric 1-(fluoro/difluorophenyl)-2-phenylethylenediamines (4-fluoro: erythro-1/threo-1; 2,4-difluoro: erythro-2/threo-2; 2,6-difluoro: erythro-3/threo-3) and the diastereomeric 1-(4-fluorophenyl)-2-(3-hydroxyphenyl)ethylenediamines (erythro-4/-threo-4) were synthesized from appropriately substituted stilbenes by reaction with IN3 and subsequent LiAlH4 reduction. Coordination of the 1,2-diphenylethylenediamines to platinum was carried out by use of K2PtI4. The water-soluble aquasulfatoplatinum(II) complexes (erythro/threo-1-PtSO4-erythro/threo-4-PtSO4) were obtained from the diiodoplatinum(II) complexes by reaction with Ag2SO4. Additionally erythro/threo-1-PtSO4 and erythro/threo-4-PtSO4 were transformed into the dichloroplatinum(II) complexes (erythro/threo-1-PtCl2, erythro/threo-4-PtCl2) by treatment with KCl. In contrast to the less effective erythro-configurated sulfatoplatinum(II) complexes the threoanalogues showed comparable or even superior activities to cisplatin on the human MDA-MB-231 breast cancer cell line. On the MXT-M-3.2 breast cancer of the mouse only erythro- and threo-4-PtSO4 caused similar effects like cisplatin. The strong inhibitory effect of the diastereomeric sulfatoplatinum(II) complexes on the P-388 leukemia of the mouse was equal to that of cisplatin. On the latter tumor threo-4-PtCl2 was the most active among the less toxic dichloroplatinum(II) derivatives.
- Gust,Schonenberger
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p. 595 - 603
(2007/10/03)
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- Compounds and process for preparing the same
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Cis and trans isomers of 1,2-diphenyl-1,2,3,4-tetrahydronaphthalenes, novel processes for the preparation thereof, and novel intermediates are disclosed herein. The novel 1,2-diphenyl-1,2,3,4-tetrahydronaphthalenes have utility as antifertility estrogenic, anti-estrogenic, anti-spermatogenic, cholesterol lowering and lipid normalizing agents.
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