[reaction: see text] Thermolysis of beta-lactam-tethered enallenyl alcohols gave tricyclic ring structures via a formal [2 + 2] cycloaddition of the alkene with the distal bond of the allene, while the tin-promoted radical cyclization in 2-azetidinone-tethered allenynes proceeded to provide bicyclic beta-lactams containing a medium-sized ring. The access to cyclization precursors was achieved by regio- and stereoselective metal-mediated carbonyl allenylation of 4-oxoazetidine-2-carbaldehydes in an aqueous environment.
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http://dx.doi.org/10.1021/ol034995c | DOI Listing |
J Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK-2100, Denmark.
NMDA receptor ligands have therapeutic potential in neurological and psychiatric disorders. We designed ()-3-(5-thienyl)carboxamido-2-aminopropanoic acid derivatives with nanomolar agonist potencies at NMDA receptor subtypes (GluN12/A-D). These compounds are superagonists at GluN1/2C compared to glycine and partial to full agonists at GluN1/2A and GluN1/2D but display functional antagonism at GluN1/2B due to low agonist efficacy.
View Article and Find Full Text PDFLangmuir
January 2025
Chemistry and Structure of novel Materials, University of Siegen, Paul-Bonatz Strasse 9-11, 57068 Siegen, Germany.
The surface charge of metal oxides is an important property that significantly contributes to a wide range of phenomena, including adsorption, catalysis, and material science. The surface charge can be predicted by determining the isoelectric point (IEP) of a material and the pH of a solution. Although there have been several studies of the IEP of metal oxide (nano)particles, only a few have reported the IEP of metal oxide films.
View Article and Find Full Text PDFPLOS Digit Health
January 2025
Cancer Registry of Norway, Norwegian Institute of Public health, Ullernchausseen 64, 0379 Oslo, Norway.
An external control arm based on health registry data can serve as an alternative comparator in single-arm drug development studies that lack a benchmark for comparison to the experimental treatment. However, accessing such observational healthcare data involves a lengthy and intricate application process, delaying drug approval studies and access to novel treatments. Clinical trials typically comprise only a few hundred patients usually with high-cardinality features, which makes individual data instances more exposed to re-identification attacks.
View Article and Find Full Text PDFPLoS Biol
January 2025
Carney Institute for Brain Science, Department of Cognitive & Psychological Sciences, Brown University, Providence, Rhode Island, United States of America.
The basal ganglia (BG) play a key role in decision-making, preventing impulsive actions in some contexts while facilitating fast adaptations in others. The specific contributions of different BG structures to this nuanced behavior remain unclear, particularly under varying situations of noisy and conflicting information that necessitate ongoing adjustments in the balance between speed and accuracy. Theoretical accounts suggest that dynamic regulation of the amount of evidence required to commit to a decision (a dynamic "decision boundary") may be necessary to meet these competing demands.
View Article and Find Full Text PDFBioinformatics
January 2025
Guangdong Provincial Key Laboratory IRADS, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, China.
Motivation: The increasing accessibility of large-scale protein sequences through advanced sequencing technologies has necessitated the development of efficient and accurate methods for predicting protein function. Computational prediction models have emerged as a promising solution to expedite the annotation process. However, despite making significant progress in protein research, graph neural networks face challenges in capturing long-range structural correlations and identifying critical residues in protein graphs.
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