23308-83-0Relevant articles and documents
Functionalized Cyclopropanes as Versatile Intermediates for the Diversity-Oriented Synthesis of γ-Lactones, γ-Lactams and δ-Lactams
Maximiano, Adrielle P.,Ramos, Giovana S.,Marques, Marcelo V.,Sá, Marcus M.
, (2021/03/18)
A two-step procedure for the preparation of cyclopropanecarboxaldehyde-1,1-diester from a γ,δ-epoxyester and its synthetic versatility are described herein. The epoxide ring-opening/cyclopropanation process occurs in the presence of Mg(ClO 4) 2under heating, resulting in cyclopropanemethanol-1,1-diester in 65% yield. A mild TEMPO-mediated oxidation of this substrate readily generated the corresponding aldehyde in 75% yield, which was applied in the one-pot synthesis of four cyclopropylidene-γ-lactams and three δ-lactams. In addition, vinylcyclopropanes were obtained through the Wittig reaction of the aldehyde with phosphonium salts and used as precursors for tetrahydrofurans.
Substituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters
Frydrych, Ivo,Urban, Milan,?arek, Jan,Benická, Sandra,D?ubák, Petr,Gurská, Soňa,Hajdúch, Marián,Kotulová, Jana,Li?ková, Barbora,Olejníková, Denisa,Pokorny, Jan
, (2021/07/28)
A set of new substituted dienes were synthesized from betulinic acid by its oxidation to 30-oxobetulinic acid followed by the Wittig reaction. Cytotoxicity of all compounds was tested in vitro in eight cancer cell lines and two noncancer fibroblasts. Almost all dienes were more cytotoxic than betulinic acid. Compounds 4.22, 4.30, 4.33, 4.39 had IC50 below 5 μmol/L; 4.22 and 4.39 were selected for studies of the mechanism of action. Cell cycle analysis revealed an increase in the number of apoptotic cells at 5 × IC50 concentration, where activation of irreversible changes leading to cell death can be expected. Both 4.22 and 4.39 led to the accumulation of cells in the G0/G1 phase with partial inhibition of DNA/RNA synthesis at 1 × IC50 and almost complete inhibition at 5 × IC50. Interestingly, compound 4.39 at 5 × IC50 caused the accumulation of cells in the S phase. Higher concentrations of tested drugs probably inhibit more off-targets than lower concentrations. Mechanisms disrupting cellular metabolism can induce the accumulation of cells in the S phase. Both compounds 4.22 and 4.39 trigger selective apoptosis in cancer cells via intrinsic pathway, which we have demonstrated by changes in the expression of the crucial apoptosis-related protein. Pharmacological parameters of derivative 4.22 were superior to 4.39, therefore 4.22 was the finally selected candidate for the development of anticancer drug.
Structural development of tetrachlorophthalimides as liver X receptor β (LXRβ)-selective agonists with improved aqueous solubility
Nomura, Sayaka,Endo-Umeda, Kaori,Fujii, Shinya,Makishima, Makoto,Hashimoto, Yuichi,Ishikawa, Minoru
, p. 796 - 801 (2018/02/09)
LXRβ-selective agonists are promising candidates to improve atherosclerosis without increasing plasma or hepatic TG levels. We have reported a series of tetrachlorophthalimide analogs as an LXRβ-selective agonist. However, they exhibited poor aqueous solubility probably due to its high hydrophobicity and highly rigid and plane structure. In this report, we present further structural development of tetrachloro(styrylphenyl)phthalimides as the LXRβ-selective agonists with improved aqueous solubility.
Development of Tetrachlorophthalimides as Liver X Receptor β (LXRβ)-Selective Agonists
Nomura, Sayaka,Endo-Umeda, Kaori,Makishima, Makoto,Hashimoto, Yuichi,Ishikawa, Minoru
, p. 2347 - 2360 (2016/10/25)
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.
Novel composite phosphonium salt as well as preparation method and antibacterial application thereof
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Paragraph 0028-0029, (2017/01/26)
The invention belongs to the technical field of fine chemical synthesis and particularly relates to a novel composite phosphonium salt as well as a preparation method and an antibacterial application thereof. The novel composite phosphonium salt adopts a
Styrylphenylphthalimides as Novel Transrepression-Selective Liver X Receptor (LXR) Modulators
Nomura, Sayaka,Endo-Umeda, Kaori,Aoyama, Atsushi,Makishima, Makoto,Hashimoto, Yuichi,Ishikawa, Minoru
supporting information, p. 902 - 907 (2015/08/24)
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.
Titanium-imido complexes with pendant groups- Synthesis, characterization, and evaluation of their role as precatalysts for ethylene polymerization
Nguyen, Viet-Hoang,Vendier, Laure,Etienne, Michel,Despagnet-Ayoub, Emmanuelle,Breuil, Pierre-Alain R.,Magna, Lionel,Proriol, David,Olivier-Bourbigou, Helene,Lorber, Christian
scheme or table, p. 97 - 111 (2012/03/13)
The synthesis of several anilines (ArPGNH2) substituted in the ortho position with pendant groups (PGs, terminated by potentially coordinative arene, thienyl, furanyl, or pyridyl functionalities) was accomplished by a two- to five-st
Ionic diamine rhodium complex catalyzed reductive N-heterocyclization of 2-nitrovinylarenes
Okuro, Kazumi,Gurnham, Joanna,Alper, Howard
experimental part, p. 4715 - 4720 (2011/07/08)
Ionic diamine rhodium complex (1) catalyzes the reductive N-cyclization of 2-vinylnitroarenes using carbon monoxide as a reducing agent to afford functionalized indoles. The catalytic system allows direct access to indoles with ester and ketone groups at the 2- or 3-position, in good yields.
Iridium-catalyzed allylic vinylation and asymmetric allylic amination reactions with o-aminostyrenes
Ye, Ke-Yin,He, Hu,Liu, Wen-Bo,Dai, Li-Xin,Helmchen, Guenter,You, Shu-Li
supporting information; experimental part, p. 19006 - 19014 (2012/01/07)
An Ir-catalyzed allylic vinylation reaction of allyl carbonates with o-aminostyrene derivatives has been realized, providing skipped (Z,E)-diene derivatives. With (E)-but-2-ene-1,4-diyl dimethyl dicarbonate as the substrate, an efficient enantioselective synthesis of 1-benzazepine derivatives via an Ir-catalyzed domino allylic vinylation/intramolecular allylic amination reaction has been developed. Mechanistic studies of the allylic vinylation reaction have been carried out, and the results suggest that the leaving group of the allylic precursor plays a key role in directing the reaction pathway. Screening of various allylic precursors showed that Ir-catalyzed reactions of allyl diethyl phosphates with o-aminostyrene derivatives proceed via an allylic amination pathway. A subsequent ring-closing metathesis (RCM) reaction of the amination products led to a series of enantiomerically enriched 1,2-dihydroquinoline derivatives. Their utility is indicated by an asymmetric total synthesis of (-)-angustureine.
Liver X receptor (LXR) modulators with dibenz[b,f]-[1,4]oxazepin-11-one, (Z)-dibenz[b,f]azocin-6-one, and 11,12-dihydrodibenz[b,f]azocin-6-one skeletons
Aoyama, Atsushi,Aoyama, Hiroshi,Makishima, Makoto,Hashimoto, Yuichi,Miyachi, Hiroyuki
scheme or table, p. 2209 - 2216 (2010/04/29)
Conformationally restricted heterocyclic analogs of carba-T0901317 with dibenz[b,f][1,4]oxazepin-11-one, 11,12-dihydrodibenz[b,f)azocin-6-one, and (Z)-dibenz[b,f]-azocin-6-one skeletons were prepared as candidate for liver X receptor (LXR) agonists. In vitro transactivation assay revealed that the activity depends on the nature of the linking group.
