Pyrrolizine-1,3-dione 4 was made by oxidation of the alcohol 2 using pyridinium chlorochromate. The dione 4 shows ketone properties (e.g. formation of DNP derivative 11) and, in common with other pyrrolizinones, the lactam unit is readily ring-opened by methanol under basic conditions. The active methylene unit of 4 couples readily with diazonium salts to provide the hydrazone 15 whose structure was confirmed by X-ray crystallography. The 'Meldrumsated' derivative 18 exists exclusively as the tautomer 18F; flash vacuum pyrolysis (FVP) of 18 at 700 degrees C gives the pyronopyrrolizine 20 exclusively. Reaction of 4 with DMF acetal gives the dimethylaminomethylene derivative 22 which exists as a mixture of rotamers at room temperature.
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http://dx.doi.org/10.1039/c0ob00116c | DOI Listing |
Alzheimers Dement
December 2024
ICMR - National Institute of Nutrition, Hyderabad, Telangana, India.
Background: Traditionally associated with recreational and spiritual uses, psychedelics have gained attention in psychotherapy for their therapeutic potential. Functioning as potent 5-hydroxytryptamine (5HT) agonists, these compounds have demonstrated the ability to enhance neural plasticity by activating serotoninergic and glutamatergic systems. Despite these recognized effects, their role in treating neurodegenerative disorders, particularly dementia, remains relatively unexplored.
View Article and Find Full Text PDFBackground: There are no cures for Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by elevation of beta-amyloid and tau proteins besides neuronal death and causing cognitive impairment. Phosphodiesterase 5 (PDE5) is a cyclic guanosine monophosphate-degrading enzyme involved in numerous biological pathways including those relevant to memory formation. PDE5 inhibition offers the potential to attenuate AD progression by acting at the downstream level of beta-amyloid and tau elevation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), site Rostock / Greifswald, Rostock, Germany.
Background: Familial Alzheimer's disease research necessitates innovative methodologies to disentangle the intricate relationships between genetic factors and neuroimaging measures. Traditional frequentist approaches, often hampered by small sample sizes in this population and challenges in incorporating prior knowledge transparently, may limit the robustness of findings.
Methods: We analyzed neuroimaging data of preclinical PSNE1 single mutation carriers, utilizing the software JASP to test effects of carrier status on measures of basal forebrain functional connectivity using both frequentist and Bayesian approach.
Alzheimers Dement
December 2024
Cleveland Clinic, Cleveland, OH, USA.
Background: Test-retest reliability for existing cognitive screening tests is typically poor and most have ceiling effects and restricted score ranges that mask the presence of subtle decline. The Brief Assessment of Cognitive Health (BACH) is a computerized cognitive screening tool that patients complete independently. It includes a complex memory test without ceiling effects and brief mood and history questions.
View Article and Find Full Text PDFCannabis
December 2024
Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton and McMaster University.
Unlabelled: Although Canada legalized cannabis beverages in 2019, most available research on acute cannabis intoxication derives from dried flower and edible products. The distinct bioavailability and pharmacokinetic properties of phytocannabinoids ingested from beverages, however, contribute to significantly different acute and long-term effects that need to be better understood to ensure consumer safety.
Objective: This review investigates existing cannabis beverage literature, with a particular focus on acute intoxication effects.
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