We demonstrate a general method for the preparation of diverse -substituted 3,4-dihydroisoquinolin-1(2)-one compounds through an overall three-step cross-coupling/cyclization/-deprotection/-alkylation sequence. In the first step, ethyl 2-bromobenzoates and 2-bromo-1-carboxyethyl heterocycles are cross-coupled with commercially available potassium (2-((-butoxycarbonyl)amino)ethyl)trifluoroborate to produce (hetero)aryl-substituted 3-[(-Boc-2-carboxyethyl)phenyl]ethylamines. In a subsequent two-stage process, these (hetero)arylethylamines undergo base-mediated ring closure followed by -deprotection and -alkylation to produce -substituted 3,4-dihydroisoquinolin-1(2)-ones and heteroaryl-fused -benzyl 3,4-dihydropyridin-2(1)-ones.
View Article and Find Full Text PDFThe preparation of metastable zeolites is often restricted to a limited range of synthesis conditions, which is exemplified in commercial syntheses lacking organics to stabilize the crystal structure. In the absence of an organic structure-directing agent, interzeolite transformation is a common phenomenon that can lead to undesirable products or impurities. Many studies have investigated the substitution of Si and Al in zeolite frameworks with alternative elements (heteroatoms) as a means of tailoring the properties of zeolites; however, relatively few studies have systematically explored the impact of heteroatoms on interzeolite transformations and their concomitant effects on zeolite crystallization.
View Article and Find Full Text PDFRough-and-tumble play (RTP) between fathers and children has been linked to many social, emotional, and behavioural child outcomes, such as reduced aggression and increased self-regulation. This study extends our understanding of the importance of RTP to the development of the executive function, working memory. Father-child dyads (N = 30) were asked to play two RTP games that were videorecorded for later observational coding.
View Article and Find Full Text PDFFather-child play engagement has been linked to a variety of child developmental outcomes. However, the most prevalent types of play and child developmental outcomes utilised in research remains unclear. The aim of this study was to systematically review the literature on father-child play interactions and the association with child developmental outcomes for children aged 0-10 years.
View Article and Find Full Text PDFExposure to early life stress has been linked to impairment in cognitive functioning in adulthood. The aim of this study was to systematically review the literature on the relationship between early life stress and working memory, a central component of cognitive functioning. Database searches yielded 358 abstracts matching the search terms.
View Article and Find Full Text PDFChildren assessed as having low working memory capacity have also been shown to perform more poorly than their same-aged peers in measures of academic achievement. Early detection of working memory problems is, therefore, an important first step in reducing the impact of a working memory deficit on the development of academic skills. In this study, we compared a single-test assessment, the Working Memory Power Test for Children (WMPT) and a multi-test assessment, the Automated Working Memory Assessment (AWMA), in their ability to predict academic achievement in reading, numeracy, and spelling.
View Article and Find Full Text PDFAntagonists of retinol-binding protein 4 (RBP4) impede ocular uptake of serum all-trans retinol (1) and have been shown to reduce cytotoxic bisretinoid formation in the retinal pigment epithelium (RPE), which is associated with the pathogenesis of both dry age-related macular degeneration (AMD) and Stargardt disease. Thus, these agents show promise as a potential pharmacotherapy by which to stem further neurodegeneration and concomitant vision loss associated with geographic atrophy of the macula. We previously disclosed the discovery of a novel series of nonretinoid RBP4 antagonists, represented by bicyclic [3.
View Article and Find Full Text PDFAccumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina.
View Article and Find Full Text PDFA new series of 5-(pyridinon-1-yl)indazoles with MCH-1 antagonist activity were synthesized. Potential cardiovascular risk for these compounds was assessed based upon their interaction with the hERG potassium channel in a mini-patch clamp assay. Selected compounds were studied in a 5-day diet-induced obese mouse model to evaluate their potential use as weight loss agents.
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