Search results for "Aminopyridines"
showing 10 items of 32 documents
Proton tautomerism in 2-nitramino-C-nitropyridine derivatives - Experimental and quantum chemical study
2019
Abstract The structures of 2-nitramino-3-nitropyridine and 2-nitramino-5-nitropyridine have been characterized by X-ray diffraction and Density Functional Theory (DFT) studies. In the crystals, both compounds exist as the imino forms. The DFT calculations were performed in order to explore the amino-imino tautomerism of the studied compounds in the gas phase and the influence of solvent polarity on the tautomeric equilibrium. The Harmonic Oscillator Model of Aromaticity index (HOMA) and Nucleus Independent Chemical Shift (NICS) calculated for the pyridine rings of the studied systems, demonstrated a noticeable decrease in aromaticity of the imino forms. This study showed also that the highe…
Protection of Flupirtine on β-Amyloid-Induced Apoptosis in Neuronal Cells In Vitro: Prevention of Amyloid-Induced Glutathione Depletion
2002
Effective drugs are not available to protect against beta-amyloid peptide (A beta)-induced neurotoxicity. Cortical neurons from rat embryos were treated with the toxic fragment A beta25-35 at 1 microM in the presence or absence of flupirtine, a triaminopyridine, successfully applied clinically as a nonopiate analgesic drug. Five days later 1 microM A beta25-35 caused reduction of cell viability to 31.1%. Preincubation of cells with flupirtine (1 or 5 microg/ml) resulted in a significant increase of the percentage of viable cells (74.6 and 65.4%, respectively). During incubation with A beta25-35 the neurons undergo apoptosis as determined by appearance of the characteristic stepladder-like D…
Neuroprotective effect of flupirtine in prion disease
2003
Apoptotic neuronal cell death is a hallmark of prion diseases. The apoptotic process in neuronal cells is thought to be caused by the scrapie prion protein, PrPSc, and can be experimentally induced by its peptide fragment, PrP106-126. This process is a target for potential drugs to combat prion disease or to ameliorate its symptoms. Flupirtine (Katadolon), a pyridine derivative that is in clinical use as a nonopioid analgesic, has a potent cytoprotective effect, at concentrations above 1 microg/mL, on neuronal cells treated with PrP(Sc) or PrP106-126. This drug acts as an N-methyl-D-aspartate (NMDA) antagonist, but does not bind to NMDA receptors. Flupirtine normalizes the level of intracel…
Enantioselective copper-aminopyridine-catalyzed aza-Henry reaction with chelating N-(2-pyridyl)sulfonyl imines
2012
This article describes a copper-catalyzed aza-Henry reaction. Copper complexes of camphor-derived aminopyridines catalyze the addition of nitromethane to N-(2-pyridyl)sulfonyl aldimines to give the corresponding β-nitrosulfonamides with good yields and variable enantiomeric excesses (up to 83%). An example of transformation of these compounds into N-(2-pyridyl)sulfonyl-α-amino acids and deprotection of the sulfonamide with Mg–MeOH is provided. Chirality 24:441–450, 2012. © 2012 Wiley Periodicals, Inc.
Effect of flupirtine on Bcl-2 and glutathione level in neuronal cells treated in vitro with the prion protein fragment (PrP106-126).
1997
Flupirtine, trade name Katadolon, is a centrally acting nonopioid analgesic that has recently been found to display cytoprotective activity in vitro and in vivo on neurons induced to undergo apoptosis. This report shows that the PrP106-126 fragment of the prion protein, which is the likely etiological agent for a series of encephalopathies, is toxic to cortical neurons in vitro. Simultaneously, PrP106-126 influences the molecular GSH content and the bcl-2 expression in neurons. Significant toxicity (32% reduction in cell viability) was observed at a concentration of 50 microM of the peptide after 9 days of incubation, while at higher concentrations toxicity increased to 70%. Neurotoxicity w…
The triaminopyridine flupirtine prevents cell death in rat cortical cells induced by N-methyl-D-aspartate and gp120 of HIV-1.
1994
Abstract Flupirtine, a triaminopyridine derivative, is a non-opiate centrally acting analgesic agent with muscle relaxant properties. Now we show that this drug displays a potent cytoprotective effect on neurons (rat cortical cells) treated with (i) the excitatory amino acid N-methyl- d -aspartate (NMDA) or (ii) with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120. In the absence of the drug the two agents cause a >90% reduction of cell viability after a 18 h incubation. During this period the DNA in the cells undergoes fragmentation and shows a pattern which is typical for cell death. If the neurons were preincubated with flupirtine for 2 h and subsequently exposed to th…
Effect of flupirtine on cell death of human umbilical vein endothelial cells induced by reactive oxygen species.
1999
Abstract Flupirtine (KATADOLON®), known as a nonopiate centrally acting analgesic drug, was tested as to its potential to prevent apoptosis of human endothelial cells induced by reactive oxygen species (ROS). It was found that Flupirtine displayed no effect on viability and cell proliferation of human umbilical vein endothelial cells (HUVEC) up to a concentration of 10 μg/mL. Apoptosis, induced by ROS and generated by hypoxanthine/xanthine oxidase (EC 1.1.3.22) (HX/XOD) or t-butyl hydroperoxide, was reduced after preincubation with Flupirtine for 3 hr by 35% and 41%, respectively. The maximal cytoprotective effect against apoptosis was observed at a drug concentration of 1 to 3 μg/mL. Flow …
Roflumilast N-oxide inhibits bronchial epithelial to mesenchymal transition induced by cigarette smoke in smokers with COPD.
2014
Abstract Background Epithelial to mesenchymal transition (EMT) is under discussion as a potential mechanism of small airway remodelling in COPD. In bronchial epithelium of COPD and smokers markers of EMT were described. In vitro, EMT may be reproduced by exposing well-differentiated human bronchial epithelial cells (WD-HBEC) to cigarette smoke extract (CSE). EMT may be mitigated by an increase in cellular cAMP. Objective This study explored the effects of roflumilast N-oxide, a PDE4 inhibitor on CSE-induced EMT in WD-HBEC and in primary bronchial epithelial cells from smokers and COPD in vitro. Methods WD-HBEC from normal donors were stimulated with CSE (2.5%) for 72 h in presence of roflum…
Simvastatin Increases the Ability of Roflumilast N-oxide to Inhibit Cigarette Smoke-Induced Epithelial to Mesenchymal Transition in Well-differentiat…
2014
Cigarette smoking contributes to epithelial-mesenchymal transition (EMT) in COPD small bronchi as part of the lung remodeling process. We recently observed that roflumilast N-oxide (RNO), the active metabolite of the PDE4 inhibitor roflumilast, prevents cigarette smoke-induced EMT in differentiated human bronchial epithelial cells. Further, statins were shown to protect renal and alveolar epithelial cells from EMT. To analyze how RNO and simvastatin (SIM) interact on CSE-induced EMT in well-differentiated human bronchial epithelial cells (WD-HBEC) from small bronchi in vitro. Methods: WD-HBEC were stimulated with CSE (2.5%). The mesenchymal markers vimentin, collagen type I and α-SMA, the e…
Microwave assisted synthesis and solid-state characterization of lithocholyl amides of isomeric aminopyridines
2011
Microwave (MW) assisted synthesis and solid state structural characterizations of novel lithocholyl amides of 2-, 3-, and 4-aminopyridine are reported. It is shown that the MW technique is a proper method in the preparation of N-lithocholyl amides of isomeric aminopyridines. It offers many advantages compared to conventional heating. The molecular and crystal structures as well as the polymorphic and hydrated forms of prepared conjugates with their thermodynamic stabilities have been characterized by means of high resolution liquid- and solid-state NMR spectroscopy, single crystal and powder X-ray diffraction, and thermogravimetric analysis. Owing to the many biological functions of bile ac…