- Design, synthesis, and biological evaluation of new growth inhibitors of Trypanosoma cruzi (epimastigotes)
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As a continuation of our project aimed at the search for new chemotherapeutic agents against Chagas' disease, several drugs structurally related to the insect growth regulator Fenoxycarb and the naturally occurring juvenfie hormone of insects were designed, synthesized, and evaluated as antiproliferative agents against the parasite responsible of this disease. Isoprenoid derivatives (compounds 33, 34, 36, and 37) were potent growth inhibitors of Trypanosoma cruzi epimastigotes. In addition, taking into account the high activity observed for compound 30 and the inhibitory action of related compounds, the allyl ether moiety bonded at the polar extreme of these inhibitors proved to be a promising group for the design of new drugs.
- Schvartzapel, Andrea J.,Zhong, Li,Docampo, Roberto,Rodriguez, Juan B.,Gros, Eduardo G.
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Read Online
- Development of novel phenoxyalkylpiperidines as high-affinity Sigma-1 (σ1) receptor ligands with potent anti-amnesic effect
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The sigma-1 (σ1) receptor plays a significant role in many normal physiological functions and pathological disease states, and as such represents an attractive therapeutic target for both agonists and antagonists. Here, we describe a novel series of phenoxyalkylpiperidines based on the lead compound 1-[ω-(4-chlorophenoxy)ethyl]-4-methylpiperidine (1a) in which the degree of methylation at the carbon atoms alpha to the piperidine nitrogen was systematically varied. The affinity at σ1 and σ2 receptors and at Δ8-Δ7 sterol isomerase (SI) ranged from subnanomolar to micromolar Ki values. While the highest-affinity was displayed at the σ1, the increase of the degree of methylation in the piperidine ring progressively decreased the affinity. The subnanomolar affinity 1a and 1-[ω-(4-methoxyphenoxy)ethyl]-4-methylpiperidine (1b) displayed potent anti-amnesic effects associated with σ1 receptor agonism, in two memory tests. Automated receptor–small-molecule ligand docking provided a molecular structure-based rationale for the agonistic effects of 1a and 1b. Overall, the class of the phenoxyalkylpiperidines holds potential for the development of high affinity σ1 receptor agonists, and compound 1a, that appears as the best in class (exceeding by far the activity of the reference compound PRE-084) deserves further investigation.
- Abatematteo, Francesca S.,Mosier, Philip D.,Niso, Mauro,Brunetti, Leonardo,Berardi, Francesco,Loiodice, Fulvio,Contino, Marialessandra,Delprat, Benjamin,Maurice, Tangui,Laghezza, Antonio,Abate, Carmen
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- GLYCOSIDE COMPOUND AND PREPARATION METHOD THEREFOR, COMPOSITION, APPLICATION, AND INTERMEDIATE
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The present invention discloses a glycoside compound represented by Formula III, and a preparation method, a composition, use and an intermediate thereof. The glycoside compound provided in the present invention has simple preparation method, can significantly increase the expression of VEGF-A mRNA, and is effective in promoting the angiogenesis. This provides a reliable guarantee for the development of drugs with pro-angiogenic activity for treating cerebral infarction cerebral stroke, myocardial infarction, and ischemic microcirculatory disturbance of lower limbs.
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Paragraph 0358-0360
(2021/04/23)
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- Visible-Light-Mediated Aerobic Oxidation of Organoboron Compounds Using in Situ Generated Hydrogen Peroxide
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A simple and general visible-light-mediated oxidation of organoboron compounds has been developed with rose bengal as the photocatalyst, substoichiometric Et3N as the electron donor, as well as air as the oxidant. This mild and metal-free protocol shows a broad substrate scope and provides a wide range of aliphatic alcohols and phenols in moderate to excellent yields. Notably, the robustness of this method is demonstrated on the stereospecific aerobic oxidation of organoboron compounds.
- Weng, Wei-Zhi,Liang, Hao,Zhang, Bo
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supporting information
p. 4979 - 4983
(2018/08/24)
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- Total synthesis of mevashuntin
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The total synthesis of (±)-mevashuntin, a structurally unique naturally occurring pyrano-naphthoquinone-thiazolone, is described. The route is centered upon a late stage regioselective Diels-Alder reaction between two highly functionalized components, as
- Nawrat, Christopher C.,Moody, Christopher J.
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supporting information; body text
p. 1484 - 1487
(2012/05/20)
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- Fragmentations observed in the reactions of α-methoxy-γ- alkoxyalkyl iodide substrates with super-electron-donors derived from 4-DMAP and N-methylbenzimidazole
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Reactions of super-electron-donors (SEDs) derived from 4- dimethylaminopyridine and from N-methylbenzimidazole with α-methoxy- γ-alkoxyalkyl iodides lead to liberation of the γ-alkoxy groups as their alcohols. This is consistent with generation of alkyl radicals from the alkyl halide precursors, and trapping of these radicals by the radical-cation of the SED, followed by a heterolytic fragmentation.
- Sword, Ryan,Baldwin, Luke A.,Murphy, John A.
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p. 3560 - 3570
(2011/06/20)
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- Novel water-soluble red-emitting poly(p -phenylenevinylene) derivative: Synthesis, characterization, and fluorescent acetylcholinesterase assays
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A new cyano-substituted poly(p-phenylenevinylene) (PPV) derivative, MEOPS-CNPPV, is synthesized through Knoevenagel condensation of anionic diacetonitrile and neutral dialdehyde and characterized by 1H NMR, IR, elemental analysis, and gel-permeation chromatography (GPC). To our knowledge, the polymer is the first water-soluble red-emitting PPV derivative. The absorption and emission wavelength of this water-soluble conjugated polymer (CP) depend on the solvent. In buffer solution, the fluorescence of MEOPS-CNPPV is quenched by cationic dinitrobenzene derivatives. Further research indicates that dinitrobenzene derivative with a more flexible structure exhibits a larger Ksv. Making use of the charge reversal of dinitrobenzene-modified substrate, a "turn-on" method is developed for AChE activity assay with the new polymer as a fluorophore. This convenient and direct fluorometric assay thus provides a platform for novel red-emitting sensory systems.
- Zhang, Wenjun,Zhu, Linna,Qin, Jingui,Yang, Chuluo
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scheme or table
p. 12059 - 12064
(2011/12/05)
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- Pyrido pyrimidinones as selective agonists of the high affinity niacin receptor GPR109A: Optimization of in vitro activity
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Pyrido pyrimidinones are selective agonists of the human high affinity niacin receptor GPR109A (HM74A). They show no activity on the highly homologous low affinity receptor GPR109B (HM74). Starting from a high throughput screening hit the in vitro activity of the pyrido pyrimidinones was significantly improved providing lead compounds suitable for further optimization.
- Peters, Jens-Uwe,Kühne, Holger,Dehmlow, Henrietta,Grether, Uwe,Conte, Aurelia,Hainzl, Dominik,Hertel, Cornelia,Kratochwil, Nicole A.,Otteneder, Michael,Narquizian, Robert,Panousis, Constantinos G.,Ricklin, Fabienne,R?ver, Stephan
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scheme or table
p. 5426 - 5430
(2010/12/25)
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- One-carbon extrusion from a tetraazafulvalene. Isolation of aldehydes and a study of their origin
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Reaction of imidazolylidene-derived enetetramine 2 with aliphatic iodides and bromides (and with aryl iodides bearing alkene-containing side-chains in the ortho-position) leads to formation of aliphatic aldehydes through an unprecedented extrusion of a one-carbon unit from the enetetramine. An intermediate 2-alkylimidazoline 24 is proposed, where the alkyl group derives from the substrate; this imidazoline undergoes further reaction in situ to afford the observed aldehydes on acidic workup. Modifiedsubstrates were designed and prepared to probe the chemistry of the alk ylimidazoline adducts and provided extensive information on the chemistry of the adducts.
- Murphy, John A.,Schoenebeck, Franziska,Findlay, Neil J.,Thomson, Douglas W.,Zhou, Sheng-ze,Garnier, Jean
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supporting information; experimental part
p. 6475 - 6479
(2009/09/26)
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- Synthesis of poly(1,4-phenylenevinylene) derivatives containing NLO chromophore within side chains
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Poly(1,4-phenylenevinylene) derivative, 58-poly(NO2STMPV-co-IMPV), consisting of poly[2-methoxy-5-{3-(4-nitrostilben-4′-yl-oxy) propoxy}phenylenevinylene] (poly(NO2STMPV)) and poly(2-isopropoxy-5-methoxy-1,4-phenylenevinylene) (poly(IMPV)) was synthesized
- Moon,Lee,Shim
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- Reactions of γ-arylalkanols via aryl radical cation and alkoxyl radical intermediates. Part 3. Reactions of 3-arylprop-1-yl hydroperoxides with iron(II) in the presence of copper(II)
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A strategy for comparing the 1,5- and 1,6-cyclisation reactions of 3-phenylpropan-1-oxyl radicals is described.Iron(II)-catalysed reduction of 3-(p-methylphenyl)prop-1-yl hydroperoxide and its para-chloro and para-methoxy-substituted analogues, carried out in the presence of copper(II), has been found to give in each case the appropriate para-substituted 3-phenylpropan-1-ol, 3-phenylpropanal and a low yield of a mixture of isomeric 6- and 7-substituted chromans.The alcohols are proposed to form via reduction of either the hydroperoxide or the resulting alkoxyl radical or its cyclised intermediates, and the aldehydes as a result of rearrangement of the alkoxyl radical to an α-hydroxy alkyl radical which subsequently undergoes oxidation.The 7-substituted chromans, which arise directly from 1,6-cyclisation of the alkoxyl radical, were found to dominate the 6-substituted isomers which result from rearrangement of 1,5-cyclised intermediates.This effect is attributed to inefficient interception of the 1,5-cyclised radical intermediate which permits equilibration to the thermodynamically more stable 1,6-cyclised radical isomer to occur.The effect of pH on the reactions has been investigated and although no products typical of the intermediacy of aryl radical cations were detected (even under highly acidic conditions), the formation of such intermediates cannot be excluded.Semiempirical MO calculations have been carried out (at the PM3 level of approximation) on a series of model compounds, yielding results which have clarified our understanding of the effect of substituents on the stabilities of the various intermediates arising from the cyclisation reactions of 3-phenylpropan-1-oxyl radicals.Furthermore, these calculations have supported our assumptions regarding the probability and specificity of rearrangements of the spirodienyl intermediates.
- Goosen, Andre,Marais, Charles F.,McCleland, Cedric W.,Rinaldi, Fabrizio C.
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p. 1227 - 1236
(2007/10/02)
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