Search results for "Benzodioxole"
showing 10 items of 13 documents
Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation and Study of Diabetic Nephropathy with Atrasentan : what …
2019
Albuminuria; Atrasentan; Canagliflozin Albuminuria; Atrasentan; Canagliflozina Albuminúria; Atrasentan; Canagliflozina In April 2019, two major Phase 3 randomized clinical trials were published that assessed primary renal outcomes in diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) tested an already available antidiabetic drug, canagliflozin, and the Study of Diabetic Nephropathy with Atrasentan (SONAR) tested a novel molecule, the endothelin-1 receptor blocker atrasentan, both on top of renin-angiotensin system blockade. Both trials demonstrated significant nephroprot…
Evaluation of Fused Pyrrolothiazole Systems as Correctors of Mutant CFTR Protein.
2021
Cystic fibrosis (CF) is a genetic disease caused by mutations that impair the function of the CFTR chloride channel. The most frequent mutation, F508del, causes misfolding and premature degradation of CFTR protein. This defect can be overcome with pharmacological agents named “correctors”. So far, at least three different classes of correctors have been identified based on the additive/synergistic effects that are obtained when compounds of different classes are combined together. The development of class 2 correctors has lagged behind that of compounds belonging to the other classes. It was shown that the efficacy of the prototypical class 2 corrector, the bithiazole corr-4a, could be impr…
Therapeutic Potential of Inhibitors of Endocannabinoid Degradation for the Treatment of Stress-Related Hyperalgesia in an Animal Model of Chronic Pain
2014
The occurrence of chronic stress, depression, and anxiety can increase nociception in humans and may facilitate the transition from localized to chronic widespread pain. The mechanisms underlying chronic widespread pain are still unknown, hindering the development of effective pharmacological therapies. Here, we exposed C57BL/6J mice to chronic unpredictable stress (CUS) to investigate how persistent stress affects nociception. Next, mice were treated with multiple intramuscular nerve growth factor (NGF) injections, which induced chronic widespread nociception. Thus, combination of CUS and NGF served as a model where psychophysiological impairment coexists with long-lasting hyperalgesia. We…
Electrochemical Synthesis of Fluorinated Orthoesters from 1,3‐Benzodioxoles
2019
Abstract Invited for this month's cover picture is the group of Professor Siegfried Waldvogel. The cover picture displays the robustness achieved by the installation of fluorinated alcohols on 1,3‐benzodioxoles, protecting the obtained orthoesters against acids and bases, like the shield of a knight. The simple protocol allows access to interesting compounds, whose lipophilicity is tremendously increased by the incorporation of fluorinated groups. This makes it possible to adjust the physicochemical properties of the biologically active 1,3‐benzodioxole motif. The surprisingly high stability against acids and bases gives rise to subsequent functionalizations or direct application in medicin…
Isomer-nonspecific action of dichlorodiphenyltrichloroethane on aryl hydrocarbon receptor and G-protein-coupled receptor 30 intracellular signaling i…
2014
Abstract Extended residual persistence of the pesticide dichlorodiphenyltrichloroethane (DDT) raises concerns about its long-term neurotoxic effects. Little is known, however, about DDT toxicity during the early stages of neural development. This study demonstrated that DDT-induced apoptosis of mouse embryonic neuronal cells is a caspase-9-, caspase-3-, and GSK-3β-dependent process, which involves p,p’ -DDT-specific impairment of classical ERs. It also provided evidence for DDT-isomer-nonspecific alterations of AhR- and GPR30-mediated intracellular signaling, including changes in the levels of the receptor and receptor-regulated mRNAs, and also changes in the protein levels of the receptors…
Elevated levels of 2-arachidonoylglycerol promote atherogenesis in ApoE-/- mice.
2018
Background The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation and ligand to both, pro-inflammatory cannabinoid receptor 1 (CB1) and anti-inflammatory CB2. While the role of both receptors in atherogenesis has been studied extensively, the significance of 2-AG for atherogenesis is less well characterized. Methods The impact of 2-AG on atherogenesis was studied in two treatment groups of ApoE-/- mice. One group received the monoacylglycerol lipase (MAGL)-inhibitor JZL184 [5 mg/kg i.p.], which impairs 2-AG degradation and thus causes elevated 2-AG levels, the other group received vehicle for four weeks. Simultaneously, both groups were fed a high-chole…
Antiatherosclerotic Effects of Small-Molecular-Weight Compounds Enhancing Endothelial Nitric-Oxide Synthase (eNOS) Expression and Preventing eNOS Unc…
2008
Many cardiovascular diseases are associated with reduced levels of bioactive nitric oxide (NO) and an uncoupling of oxygen reduction from NO synthesis in endothelial NO synthase (eNOS uncoupling). In human endothelial EA.hy 926 cells, two small-molecular-weight compounds with related structures, 4-fluoro-N-indan-2-yl-benzamide (CAS no. 291756-32-6; empirical formula C16H14FNO; AVE9488) and 2,2-difluoro-benzo[1,3]dioxole-5-carboxylic acid indan-2-ylamide (CAS no. 450348-85-3; empirical formula C17H13F2NO3; AVE3085), enhanced eNOS promoter activity in a concentration-dependent manner; with the responsible cis-element localized within the proximal 263 base pairs of the promoter region. RNA int…
Front Cover: Electrochemical Synthesis of Fluorinated Orthoesters from 1,3‐Benzodioxoles (ChemistryOpen 9/2019)
2019
The Front Cover shows the robustness achieved by the installation of fluorinated alcohols on 1,3‐benzodioxoles, which appears like the shield of a knight protecting the obtained orthoesters against acids and bases. The simple protocol allows access to interesting compounds, whose lipophilicity is tremendously increased by the incorporation of fluorinated groups. This makes it possible to adjust the physicochemical properties of the biologically active 1,3‐benzodioxole motif. The surprisingly high stability against acids and bases gives rise to subsequent functionalizations or direct application in medicinal or agrochemistry. More information can be found in the Communication by J. L. Röckl …
Cross-reinstatement between 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using conditioned place preference.
2019
Abstract 3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) considered to be a cocaine-like psychostimulant. The substitution of an established illicit drug as cocaine with an NPS is a pattern of use reported among drug users. The aim of this study was to investigate the relationship between cocaine and MDPV in the reinstatement of the conditioned place preference (CPP) paradigm, in order to establish whether there is cross-reinstatement between the two psychostimulants. Four experimental groups of male OF1 mice were subjected to the CPP paradigm: MDPV-MDPV, Cocaine-Cocaine, Cocaine-MDPV, and MDPV-Cocaine. The first drug refers to the substance with which the animal…
Behavioural and neurochemical effects after repeated administration of N-ethylpentylone (ephylone) in mice
2022
N-ethyl-pentylone (NEP), also known as "ephylone" and N-ethylnorpentylone, has been identified as one of the most recent novel psychostimulants to emerge into the illicit drug market and it has been associated with some intoxications and even fatalities. However, little is known about the consequences of its repeated consumption as well as the role of the monoaminergic system in such consequences. Thus, the aim of our study was to investigate the neurochemical profile and the behavioural effects after both acute and repeated NEP exposure. Male OF1 mice were acutely (1, 3, 10 mg/kg, i.p.) or repeatedly (1, 3, 10 mg/kg, i.p., 5 days, twice/day) exposed to NEP, and anxiety-like behaviour, aggr…