Title:Aminopyridines and Acetyl-DL-leucine: New Therapies in Cerebellar Disorders. VOLUME: 17 ISSUE: 1. Author(s):Roger Kalla and Michael Strupp*. Affiliation:Department of Neurology, German Center for Vertigo and Balance Disorders, and Institute for Clinical Neurosciences, University Hospital Munich, Campus Grosshadern, Munich, Department of Neurology, German Center for Vertigo and Balance Disorders, and Institute for Clinical Neurosciences, University Hospital Munich, Campus Grosshadern, Munich. Keywords:Cerebellar ataxia, central vestibular disorders, aminopyridines, 4-aminopyridine, episodic ataxia type 2, downbeat nystagmus, acetyl-DL-leucine.. Abstract:Cerebellar ataxia is a frequent and often disabling syndrome severely impairing motor functioning and quality of life. Patients suffer from reduced mobility, and restricted autonomy, experiencing an even lower quality of life than, e.g., stroke survivors. Aminopyridines have been demonstrated viable for the symptomatic treatment of certain ...
4-Aminopyridines undergo surprisingly rapid and highly-selective H/D exchange at C-2 and C-6 in neutral D2O upon microwave irradiation at only 190 °C for 2 h in a sealed vessel. This method contrasts and complements acid-mediated H/D exchange, requires no catalyst and is appropriate for the synthesis of deuterium isotop-ologues of N- and C-substituted 4-aminopyridines and a ben-zofused (quinoline) analogue.. ...
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Top Quality 99% Amlexanox Cas:68302-57-8 Amlexanox English name: Amlexanox Amlexanox CAS Number: 68302-57-8 Amlexanox Molecular formula: C16H14N2O4 Amlexanox Molecular weight: 298.29 Amlexanox EINECS number: Amlexanox Related categories:...
This paper describes a protocol for imidazo[1,2-a]pyridine-2-carboxylic acids synthesis directly from condensation of substituted 2-aminopyridines and bromopyruvic acid. The recipe is applicable to a wide range of aminopyridines and can be telescoped with an amide formation to obtain Imidazo[1,2-a]pyridine-2-carboxamides in one continuous process.. ...
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In people whos cancers have a PIK3CA mutation, this trial will be evaluating the drug BKM120 as a possible treatment. BKM120 works by blocking the phosphatidylinositol-3-kinase (PI3K)pathway, thereby inhibiting tumor growth and survival.. The purpose of this study is to learn if the study drug BKM120 can shrink or slow the growth of your tumor. The safety of BKM120 will also be studied. Your physical state, symptoms, change in the size of your tumor, and laboratory findings obtained while you are on study will help the research team decide if BKM120 is safe and effective in patients with advanced cancers. ...
Abstract: The lymphoid neoplasms are a heterogeneous group of diseases caused by genetic alterations that were originated from hematopoietic progenitor cells of lymphoid origin, leading to uncontrolled clonal proliferation of B or T cells, and to the development of lymphoid leukemias and lymphomas. These findings emphasize the involvement of different signaling pathways involved in both the development and the maintenance of hematological malignancies. Constitutive activation of the PI3K /AKT/mTOR signaling pathway is well described for acute lymphoblastic leukemia T cells (T-ALL), recently been identified in animal models, that the activity of PI3K cooperates with the development of Burkitts lymphoma (LB).Thus, the role of the PI3K / AKT / mTOR pathway in cell growth and survival, two important features of leukemogenesis, morphed into a potential drug target. Following this perspective, the present study aimed to evaluate the therapeutic potential of NVP-BKM120, a pan-PI3K inhibitor class I in ...
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LAWSON, Kim (2018). Flupirtine is an effective analgesic: is the associated rare liver injury a limiting factor to its use? Anesthesia and Analgesia. Full text not available from this repository ...
Flupirtine is a pyridine derivative that is in clinical use as a nonopioid analgesic. It was approved for the treatment of pain in 1984 in Europe. It is not approved for use in the U.S. or Canada, but is currently in phase II trials for the treatment of fibromyalgia.
There is a need to improve treatments for metastatic breast cancer. Here we show activation of the phosphoinositide 3-kinase (PI3K) and MAP kinase (MAPK) pathways in a MMTV-CreBRCA1f/fp53+/- mouse model of breast cancer. When treated with the pan-Class IA PI3K-inhibitor NVP-BKM120, tumor doubling was delayed from 5 to 26 days. NVP-BKM120 reduced AKT phosphorylation, tumor cell proliferation and angiogenesis. Resistant tumors maintained suppression of AKT phosphorylation but exhibited activation of the MAPK-pathway at the "pushing margin". Surprisingly, PI3K-inhibition increased indicators of DNA damage, poly-ADP-ribosylation and γH2AX, but decreased Rad51 focus formation, suggesting a critical role of PI3K activity for Rad51 recruitment. PARP-inhibitor Olaparib alone attenuated tumor growth modestly; however, the combination of NVP-BKM120 and Olaparib delayed tumor doubling to more than 70 days in the mouse model and over 50 days in xenotransplants from human BRCA1-related tumors, suggesting ...
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In the reaction of 2,6-dichloropyridine and 2,6-dichloro-3-phenylpyridine with potassium amide in liquid ammonia at -70°C, formation of derivatives of 4,4-bipyridyl and 3,4-bipyridyl is observed. The 4,4 coupling products are far in excess to the 3,4 coupling products. When the reaction is carried out at -70°C in the presence of potassium permanganate, the corresponding 4-aminopyridines are the main products. 2-Chloro-6-phenoxypyridine is very unreactive with this aminating reagent at -70°C as well as -33°C, but in the presence of potassium permanganate at -33°C 4-amino-2-chloro-6-phenoxypyridine is formed in fair yield. The mechanisms of the formation of the bipyridyls and 4-aminopyridines are presented.. ...
2013 American Chemical Society. This is the author created version of a work that has been peer reviewed and accepted for publication by Organometallics, American Chemical Society. It incorporates referees comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1021/om400326c ...
Rationale Roflumilast is an investigational PDE4 inhibitor for potential asthma therapy. Inhibitory effects of roflumilast on allergen-induced early airway response (EAR), late airway hyperresponsiveness (AHR), and inflammatory cells were investigated in a fungal allergen model of asthma in BALB/c mice. Methods Mice were sensitized with Aspergillus fumigatus extract (Afu) and adjuvant (i.p. and s.c. both on Day 0). After 2 inhalation boosts with Afu aerosol on Days 14 and 21, animals were Afu aerosol challenged on Day 23. Before each Afu aerosol exposure, animals received i.g. 1mg/kg or 5mg/kg roflumilast. For EAR, lung resistance was measured by body plethysmography in orotracheally intubated mice. AHR against aerosolized methacholine was determined 24 h after challenge by head-out plethysmography. Bronchoalveolar lavage (BAL) was done 25 h after challenge and differential cell count was determined. Results Afu-sensitized and -challenged mice showed pronounced EAR, AHR, and pulmonary ...
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Abstract : 2-Aminopyridine (2-AP) and 2,6-diaminopyridine (2,6-DAP) are two derivatives of aminopyridines that act as animportant organic intermediates, mostly used in medicines, dyes and organic sensors. The aim of the study was to evaluate theimpact of biofield energy treatment on isotopic abundance ratios of 2H/1H, 13C/12C, or 15N/14N, in aminopyridine derivativesusing gas chromatography-mass spectrometry (GC-MS). The 2-AP and 2,6-DAP samples were divided into two parts: controland treated. The control sample remained as untreated, while the treated sample was further divided into four groups as T1, T2,T3, and T4. The treated group was subjected to Mr. Trivedis biofield energy treatment. The GC-MS spectra of 2-AP and 2,6-DAP showed five and six m/z peaks respectively due to the molecular ion peak and fragmented peaks of aminopyridinederivatives. The isotopic abundance ratio of 2H/1H, 13C/12C, or 15N/14N were calculated for both the derivatives and significantalteration was found in the ...
Methapyrilene is an antihistamine and anticholinergic of the pyridine chemical class which was developed in the early 1950s. It was sold under the trade names Co-Pyronil and Histadyl EC.[1] It has relatively strong sedative effects, to the extent that its primary use was as a medication for insomnia rather than for its antihistamine action. Together with scopolamine, it was the main ingredient in Sominex, Nytol, and Sleep-Eze. It also provided the sedative component of Excedrin PM. All of these products were reformulated in the late 1970s when methapyrilene was demonstrated to cause liver cancer in rats when given chronically.[2] ...
Aminopyridines have recently become the focus of extensive studies, mainly because of their wide use as building blocks for synthetic transformations (Peng et al., 2001; Leung et al., 2002). Carboxylic acids are important in crystal engineering due to their strong and directional O-H···O and N-H···O hydrogen bonds; this is the main hydrogen-bonding motif often encountered in carboxylic acid-amine complexes (Banerjee & Murugavel, 2004; Lautie & Belabbes, 1996). Here, we report the synthesis and crystal structure of the title compound, (I).. The asymmetric unit of the title compound, (Fig 1), contains one 2,3-diaminopyridinium cation, one sorbate anion and one neutral sorbic acid molecule. The 2,3-diaminopyridinium cation is planar with a maximum deviation of 0.013 (2) Å for atom C2. Protonation of atom N1 has resulted in a slight increase in the angle C1-N1-C5 [123.71 (17)°]. The sorbate anion and sorbic acid moiety is in the EE configuration. The structure is significantly different ...
PRIMARY OBJECTIVES:. I. To determine the maximum tolerated dose (MTD) of BKM120 (PI3K inhibitor BKM120) in combination with fulvestrant.. II. To evaluate the toxicity profile of BKM120 in combination with fulvestrant.. SECONDARY OBJECTIVES:. I. To evaluate the toxicity profile of BKM120 in combination with fulvestrant when administered for at least 3 months.. II. To determine the steady state blood concentrations of BKM120 when combined with fulvestrant.. III. To evaluate the anti-tumor effect (partial response [PR], complete response [CR], stable disease [SD], and progressive disease [PD]) of BKM120 in combination with fulvestrant in patients with ER+ metastatic breast cancer.. TERTIARY OBJECTIVES:. I. To examine baseline tumor specimens for phosphatidylinositol 3-kinase (PI3K) pathway abnormalities, and to correlate with treatment response.. II. To examine the PIK3 catalytic alpha polypeptide (PIK3CA) mutation status in circulating deoxyribonucleic acid (DNA) at baseline and following study ...
... is the active ingredient in a common topical treatment for recurrent aphthous ulcers of the mouth (canker sores),[2] reducing both healing time[3] and pain.[4] Amlexanox 5% paste is well-tolerated,[5] and is typically applied four times per day directly on the ulcers.[3] A 2011 review found it to be the most effective treatment of the eight treatments investigated for recurrent canker sores.[6] It is also used to treat ulcers associated with Behçet disease.[7]. In Japan, it is used to treat bronchial asthma, allergic rhinitis and conjunctivitis.[8]. Although it is one of the only effective treatments known for apthous stomatitis, the company that claims to have the rights to the drug, Uluru Inc., is either unwilling or incapable of manufacturing it. The company has not responded to patients who have pleaded for help in obtaining the medication for relief from this often debilitating condition.. ...
Lawrence LeBlond for redOrbit.com - Your Universe Online. A drug that is normally prescribed for asthma patients is breathing new life as a potential treatment option for people who suffer from diabetes and obesity. The drug, amlexanox, was demonstrated to reverse obesity, diabetes and fatty liver in mice in a new study, published this week in the journal Nature Medicine.. The finding comes from the research lab of Alan Saltiel, the Mary Sue Coleman director of the Life Sciences Institute at the University of Michigan. Saltiel explained that amlexanox is currently prescribed to treat asthma in Japan and canker sores in the US, but the new research shows that it may also be a viable option for treatment of obesity and diabetes.. "One of the reasons that diets are so ineffective in producing weight loss for some people is that their bodies adjust to the reduced calories by also reducing their metabolism, so that they are defending their body weight," Saltiel said in a statement. "Amlexanox seems ...
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[107 Pages Report] Check for Discount on Global 2-Aminopyridine Market Professional Survey Report 2016 report by QYResearch Group. This report Mainly covers the following product types The segment...
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PubMed journal article PDE4 inhibitors roflumilast and rolipram augment PGE2 inhibition of TGF-{beta}1-stimulated fibroblast were found in PRIME PubMed. Download Prime PubMed App to iPhone or iPad.
Identification of Degradation Products in the Phosphodiesterase (PDE-4) Inhibitor Roflumilast Using High Resolution Mass Spectrometry and Density Functional Theory Calculations;kpubs;kpubs.org
TY - JOUR. T1 - Activation of rat thymocytes selectively upregulates the expression of somatostatin receptor subtype-1. AU - Sedqi, M.. AU - Roy, Sabita. AU - Mohanraj, D.. AU - Ramakrishnan, Sundaram. AU - Loh, H. H.. PY - 1996/10/22. Y1 - 1996/10/22. N2 - Somatostatin and other neuropeptides are known to modulate the proliferative capacity of immune cells. In the present study, we investigated the expression of Somatostatin receptor (SSTR) subtypes on rat thymocytes. RT-PCR analysis of fresh thymocytes showed significant levels of transcripts for the SSTR2 whereas transcripts for the SSTR1 and SSTR3 were not detectable. Interestingly, when the thymocytes were activated with low concentration of Phytohemagglutinin and interleukin 1, the transcript for SSTR1 was markedly increased. Lymphokine induced activation of thymocytes selectively upregulated the SSTR1 since, transcripts for SSTR2 remained the same after activation and SSTR3 was not detectable. PCR amplified fragment of SSTR1 from the ...
There is limited real-world evidence of the demographic and clinical characteristics, as well as resource utilizations and associated costs, among COPD patients who were on roflumilast vs other maintenance combination medications. Results from this study indicate that, at baseline, most patients in the roflumilast cohort use roflumilast along with other maintenance medications as combination therapy. The roflumilast cohort showed a larger proportion of patients with ,3 drug classes in their combination therapy, a greater comorbidity burden, more severe COPD conditions, and higher exacerbation history compared with the nonroflumilast cohort. These results are not unexpected. Roflumilast is a relatively new drug indicated for the treatment of severe COPD, and previous research has suggested that newer drugs are more likely to be prescribed to patients who have failed to respond to other treatments, tend to be sicker, or both (Schneeweiss 2011). In addition, the GOLD guidelines recommend adding ...
Reilly SM, Chiang SH, Decker SJ, et al. An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice. Nat Med. 2013 Mar;19(3):313-21. PMID: 23396211.. Bell J. Amlexanox for the treatment of recurrent aphthous ulcers. Clin Drug Investig. 2005;25(9):555-66. PMID: 17532700.. Landriscina M, Prudovsky I, Mouta Carreira C, et al. Amlexanox reversibly inhibits cell migration and proliferation and induces the Src-dependent disassembly of actin stress fibers in vitro. J Biol Chem. 2000 Oct 20;275(42):32753-62. PMID: 10921913.. Shishibori T, Oyama Y, Matsushita O, Yet al. Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family. Biochem J. 1999 Mar 15;338 ( Pt 3):583-9. PMID: 10051426.. Makino H, Saijo T, Ashida Y, et al. Mechanism of action of an antiallergic agent, amlexanox (AA-673), in inhibiting histamine release from mast cells. Acceleration of cAMP generation and inhibition of ...
Roflumilast has been shown to reduce exacerbations in patients at risk of these episodes, but whether this occurs on top of the effect of other therapy has been less clear. In this pre-specified combined analysis of data from two large randomised clinical trials, roflumilast decreased the rate of COPD exacerbations and improved lung function (pre- and post-bronchodilator FEV1) despite concomitant treatment with LABAs. In addition, the time to onset of the first, second and third moderate or severe exacerbation was delayed by roflumilast regardless of concomitant LABA use, while the frequency of adverse events associated with roflumilast treatment was not different in those with or without LABAs. The relative reduction in moderate or severe exacerbation rates in patients treated with LABAs was 20.7% and the corresponding number needed to treat with roflumilast to prevent one moderate or severe exacerbation per year was low (3.2).. Although the treatment effect of roflumilast together with ...
[101 Pages Report] Check for Discount on Global Amlexanox Market Research Report 2017 report by QYResearch Group. In this report, the global Amlexanox market is valued at...
The goal of this clinical research study is to learn if BKM120 (buparlisib) can help to control glioblastoma and/or gliosarcoma. Researchers also want to learn more about how much study drug is in different areas of the body at different time points. The safety of this drug will also be studied. BKM120 is designed to block a protein that is important to the growth and division of cancer cells, which may cause the cells to die.
This pilot study will investigate the efficacy and tolerability of BKM 120 for the treatment of refractory or residual aggressive B-cell non-Hodgkin lymphoma.
The purpose of this study is to find out the good and bad effects that occur when BKM120 is added to standard chemotherapy with carboplatin and paclitax
Dallas, Texas (PRWEB) March 03, 2015 -- Founded in 2010 with only seven employees, BKM Sowan Horan has continued a rapid ascent into consideration among the
45. At least one chemical entity of claim 1 wherein the compound of Formula 1 is selected frommethyl 4-[(2-fluoro-3-{[(6-methyl(3-pyridyl))amino]carbonylamino}phenyl)methyl]p- iperazinecarboxylate;N-({3-fluoro-5-[(3-pyridylamino)carbonylamino]phenyl}- methyl)methoxy-N-methylcarboxamide;N-[(3-fluoro-5-{[(6-methyl(3-pyridyl))a- mino]carbonylamino}phenyl)methyl]methoxy-N-methylcarboxamide;N-[3-({[(dime- thylamino)sulfonyl]methylamino}methyl)-5-fluorophenyl](3-pyridylamino)carb- oxamide;N-[3-({[(dimethylamino)sulfonyl]methylamino}methyl)-5-fluorophenyl- ][(6-methyl(3-pyridyl))amino]carboxamide;N-(3-({[(ethylsulfonyl)methylamin- o]methyl)-5-fluorophenyl)[(6-methyl(3-pyridyl))amino]carboxamide;methyl 4-({3-fluoro-5-[(3-pyridylamino)carbonylamino]phenyl}methyl)piperazinecar- boxylate;N-(3-{[4-(ethylsulfonyl)piperazinyl]methyl}-5-fluorophenyl)(3-pyr- idylamino)carboxamide;methyl 4-[(3-fluoro-5-{[(6-methyl(3-pyridyl))amino]carbonylamino}phenyl)methyl]p- ...
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Roflumilast is a targeted, oral, once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in COPD. Results from in vitro studies with roflumilast indicate that roflumilast has anti-inflammatory properties that may be applicable for the treatment of COPD. In this cross-over study, 38 patients with COPD (mean (SD) age 63.1 (7.0) y, post-bronchodilator FEV1 61.0 (12.6) %predicted) received 500 μg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected prior to and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly. Roflumilast significantly reduced the absolute number of neutrophils and eosinophils per gram of sputum, compared with placebo, by 35.5% (95%CI 15.6, 50.7; p=0.0017) and 50.0% (26.8, 65.8; p=0.0005), respectively. The relative proportion of sputum neutrophils and ...
0055]The matrix in which the aminopyridine is homogeneously dispersed provides a sustained release of the aminopyridine into the plasma of the patient. Polymeric matrices suitable for controlling the release rate of aminopyridines for use in the pharmaceutical compositions of the present invention include hydrophilic polymers; hydrophobic polymers or mixtures of hydrophilic and/or hydrophobic polymers that are capable of forming sustained-release dosage formulation in combination with an aminopyridine. Such matrices are also capable of preventing degradation and loss of the aminopyridine from the composition. Examples of suitable matrices either alone or in combination include but are not limited to hydroxyalkylcelluloses, such as hydroxypropylcellulose and HPMC, hydroxyethyl cellulose, alkylcelluloses such as ethycellulose and methylcellulose, carboxymethylcellulose; sodium carboxymethylcellulose, hydrophilic cellulose derivatives, polyethylene oxide, polyethylene glycol, polyvinylpyrrolidone; ...
Professor Michael Strupp, MD, FRCP, FANA, FEAN is a Scientific Founder and Consultant for IntraBio Inc. Professor Strupp is a Professor at the University of Munich, Germany in the Department of Neurology and German Centre for Vertigo and Balance Disorders. His expertise is in therapy for vestibular, ocular motor, and cerebellar disorders. Professor Strupps research has demonstrated the effectiveness of vestibular exercises in acute vestibular neuritis in a controlled clinical trial, and introduced three new therapeutic principles: aminopyridines, as potassium channel blockers, for the treatment of downbeat, upbeat and central positioning nystagmus as well as episodic ataxia type 2; chlorzoxazone for the therapy of downbeat nystagmus; and, more recently, acetyl-DL-leucine for the treatment of ataxias and Niemann-Pick Type C. His study demonstrating the benefit of steroids in acute vestibular neuritis, a placebo-controlled, four-arm trial was published in the NEJM. Currently, Professor Strupp is ...
Molecular imprinted polymer against nicotine was prepared and its binding affinity and selectivity to nicotine were evaluated by batch adsorption experiments. Nicotine-imprinted polymer exhibited higher affinity to nicotine compared to non-imprinted polymer; Scatchard analysis indicated that there were two classes of recognition sites in nicotine-imprinted polymer, which had different affinity to nicotine. Furthermore, compared to the adsorption behaviors of aminopyridines, nicotine-imprinted polymer displayed satisfying selectivity. The results in this study proved the possibility to selectively extract nicotine from tobacco smoke when the nicotine-imprinted polymer was used as solid-phase extraction material.
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Roflumilast reduces inflammation in the lungs that leads to COPD (chronic obstructive pulmonary disease). Roflumilast is used to prevent worsening of symptoms in people with severe chronic obstructive pulmonary disease (COPD). Roflumilast is not a bronchodilator. It will not treat a bronchospasm attack that has already...