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Search Results: 1 - 10 of 303935 matches for " Eliezer J.;Miranda "
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The synthesis of new isochromanylacetylarylhydrazones designed as probable non-addictive analgesic agents
Santos, Margareth R?se L.;Barreiro, Eliezer J.;Braz-Filho, Raimundo;Miranda, Ana Luisa P.;
Journal of the Brazilian Chemical Society , 1997, DOI: 10.1590/S0103-50531997000500007
Abstract: the synthesis and pharmacological profile as analgesic and anti-inflammatory agents of new isochromanylacetylarylhydrazone derivatives (3) are described in this paper. the synthetic route used in this work to construct the heterocyclic six member ring explored a lewis acid-catalyzed cyclization process as the key step, which represents a modified friedel-crafts reaction. these new derivatives (3) were obtained in ca. 85 % overall yields from the starting material safrole (4), an abundant natural product isolated from sassafras oil. the nmr spectral analysis of these new derivatives indicated, at the c=n double bond level, the diastereomeric nature in a 70:30 ratio, where the major compound is the (e)-isomer. the results obtained from the pharmacological evaluation of (3) using the carrageenan-induced rat paw edema test and the acetic acid solution-induced constrictions in mouse test, indicated the pharmacophoric nature of the acylarylhydrazone moiety to the analgesic activity observed in this series.the role of the aryl substituents in the bioactivity seems to indicate that the presence of hydrophobic groups may improve the analgesic profile. these new isochromanylacetylarylhydrazone derivatives (3) represent a new class of non-addictive analgesic agents.
A química medicinal de N-acilidrazonas: novos compostos-protótipos de fármacos analgésicos, antiinflamatórios e anti-trombóticos
Barreiro, Eliezer J.;Fraga, Carlos A. M.;Miranda, Ana L. P.;Rodrigues, Carlos R.;
Química Nova , 2002, DOI: 10.1590/S0100-40422002000100022
Abstract: in this article are described new bioactive n-acylhydrazone (nah) derivatives, structurally designed as optimization of aryl hydrazones precursors planned by molecular hybridization of two 5-lipoxigenase inhibitors, e.g. cbs-1108 and bw-755c. the analgesic, antiedematogenic and anti-platelet aggregating profile of several isosteric compounds was investigated by using classic pharmacological assays in vivo and ex-vivo, allowing to identify new potent peripheric analgesic lead, a new anti-inflammatory and an antithrombotic agent. during this study was discovered dozen of active nah compounds clarifying the structure-activity relationship for this series of nah derivatives, indicating the pharmacophore character of the n-acylhydrazone functionality.
A química medicinal de N-acilidrazonas: novos compostos-protótipos de fármacos analgésicos, antiinflamatórios e anti-trombóticos
Barreiro Eliezer J.,Fraga Carlos A. M.,Miranda Ana L. P.,Rodrigues Carlos R.
Química Nova , 2002,
Abstract: In this article are described new bioactive N-acylhydrazone (NAH) derivatives, structurally designed as optimization of aryl hydrazones precursors planned by molecular hybridization of two 5-lipoxigenase inhibitors, e.g. CBS-1108 and BW-755c. The analgesic, antiedematogenic and anti-platelet aggregating profile of several isosteric compounds was investigated by using classic pharmacological assays in vivo and ex-vivo, allowing to identify new potent peripheric analgesic lead, a new anti-inflammatory and an antithrombotic agent. During this study was discovered dozen of active NAH compounds clarifying the structure-activity relationship for this series of NAH derivatives, indicating the pharmacophore character of the N-acylhydrazone functionality.
New antithrombotic aryl-sulfonylthiosemicarbazide derivatives synthesized from natural safrole
Lima, Lídia M.;Ormelli, Claudia B.;Fraga, Carlos A.M.;Miranda, Ana L.P.;Barreiro, Eliezer J.;
Journal of the Brazilian Chemical Society , 1999, DOI: 10.1590/S0103-50531999000500013
Abstract: as part of a research program aiming at the synthesis and pharmacological evaluation of novel lead-compounds exploring brazilian abundant natural products, we describe herein the synthesis and the antithrombotic profile of new aryl-sulfonylsemicarbazides and aryl-sulfonylthiosemicarbazides (10a-d). the new derivatives, designed with basis on the molecular hybridization concept, were prepared in good yields from natural safrole (9), isolated from sassafras oil. the anti-aggregating activity of these new derivatives (10a-d) on platelet aggregation induced by adp, collagen, arachidonic acid and u-46619, indicates an important antithrombotic profile for the 6-methyl-3,4-methylenedioxyphenyl-sulfonyl-n-phenylthiosemicarbazide derivative (10d), acting at the arachidonic acid cascade and representing a new lead-compound with antithrombotic activity.
Discovery of Novel Orally Active Anti-Inflammatory N-Phenylpyrazolyl-N-Glycinyl-Hydrazone Derivatives That Inhibit TNF-α Production
Renata B. Lacerda, Leandro L. da Silva, Cleverton K. F. de Lima, Eduardo Miguez, Ana Luisa P. Miranda, Stefan A. Laufer, Eliezer J. Barreiro, Carlos A. M. Fraga
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046925
Abstract: Herein, we describe the synthesis and pharmacological evaluation of novel N-phenylpyrazolyl-N-glycinyl-hydrazone derivatives that were designed as novel prototypes of p38 mitogen-activated protein kinase (MAPK) inhibitors. All of the novel synthesized compounds described in this study were evaluated for their in vitro capacity to inhibit tumor necrosis factor α (TNF-α production in cultured macrophages) and in vitro MAPK p38α inhibition. The two most active anti-TNF-α derivatives, (E)-2-(3-tert-butyl-1-phenyl-1H-pyrazol-5-ylamino)-N’-((4-(2-morpholinoethoxy)naphthalen-1-y?l)methylene)acetohydrazide(4a) and (E)-2-(3-tert-butyl-1-phenyl-1H-pyrazol-5-ylamino)-N’-(4-chlorobenzylid?ene)acetohydrazide(4f), were evaluated to determine their in vivo anti-hyperalgesic profiles in carrageenan-induced thermal hypernociception model in rats. Both compounds showed anti-inflammatory and antinociceptive properties comparable to SB-203580 used as a standard drug, by oral route at a dose of 100 μmol/kg. This bioprofile is correlated with the ability of NAH derivatives (4a) and (4f) suppressing TNF-α levels in vivo by 57.3 and 55.8%, respectively.
Therapeutic approaches for tumor necrosis factor inhibition
Barbosa, Maria Letícia de Castro;Fumian, Milla Machado;Miranda, Ana Luísa Palhares de;Barreiro, Eliezer J.;Lima, Lídia Moreira;
Brazilian Journal of Pharmaceutical Sciences , 2011, DOI: 10.1590/S1984-82502011000300002
Abstract: tumor necrosis factor (tnf) consists of an inflammatory cytokine essential for homeostasis and organism defense. despite its physiological relevance, both increased biosynthesis and release of tnf lead to the exacerbation of inflammatory and oxidative responses, which are related to the pathogenesis of a host of diseases of an inflammatory, autoimmune and/or infectious nature. in this context, effective therapeutic approaches for the modulation of tnf have been the focus of research efforts. approximately one million individuals worldwide have been treated with biotechnological inhibitors of this cytokine, the so-called anti-tnf biopharmaceuticals. however, given the high risk of infection and the limitations related to cost and administration routes, new therapeutic approaches aimed at biological targets that directly or indirectly modulate the production and/or activation of tnf appear promising alternatives for the discovery of new anti-inflammatory and immunomodulatory orally active drugs and are therefore discussed in this paper.
Novel Potent Imidazo[1,2-a]pyridine-N-Glycinyl-Hydrazone Inhibitors of TNF-α Production: In Vitro and In Vivo Studies
Renata B. Lacerda, Natália M. Sales, Leandro L. da Silva, Roberta Tesch, Ana Luisa P. Miranda, Eliezer J. Barreiro, Patricia D. Fernandes, Carlos A. M. Fraga
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091660
Abstract: In this work, we describe the design, synthesis and pharmacological evaluation of novel imidazo[1,2-a]pyridine-N-glycinyl-hydraz?onederivatives (1a–k) intended for use as inhibitors of tumor necrosis factor alpha (TNF-α) production. The compounds were designed based on the orally active anti-inflammatory prototype LASSBio-1504 (2), which decreases the levels of the pro-inflammatory cytokine TNF-α in vitro and in vivo. The in vitro pharmacological evaluation of the imidazo[1,2-a]pyridine compounds (1) showed that substitution of the N-phenylpyrazole core present in prototype 2 by a bioisosteric imidazo[1,2-a]pyridine scaffold generated anti-TNF-α compounds that were more potent than the previously described N-phenylpyrazole derivative 2 and as potent as SB-203580, a p38 MAPK inhibitor. The most active derivative (E)-2-(2-tert-butylimidazo[1,2-a]pyridin?-3-ylamino)-N’-(4-chlorobenzylidene)acetohydrazide, or LASSBio-1749 (1i) was orally active as an anti-inflammatory agent in a subcutaneous air pouch model, reducing expressively the levels in vivo of TNF-α and other pro-inflammatory cytokines at all of the tested doses.
Estratégia de simplifica??o molecular no planejamento racional de fármacos: a descoberta de novo agente cardioativo
Barreiro, Eliezer J.;
Química Nova , 2002, DOI: 10.1590/S0100-40422002000700018
Abstract: in this article are described examples of the successful use of molecular simplification strategy in the discovery of new drugs from bioactive natural products and synthetic compounds. the discovery of a new cardiotonic derivative (37, 2-thienylidene-3,4-methylenedioxybenzoylhydrazine; lassbio-294), efficiently synthesized from brazilian natural product and structurally designed by molecular simplification of active pyridazinone compounds reported in the literature, is described. a brief description of the pharmacological profile of this new cardiotonic lead-compound, belonging to the n-acylhydrazone (nah) class, is also reported herein.
Editorial
Barreiro Eliezer J.
Química Nova , 2001,
Abstract:
Abstract
Barreiro Eliezer J.
Química Nova , 2002,
Abstract:
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