The synthesis of a range of novel amine-containing structures and their primary potency as inhibitors of HIV-1 fusion via blocking of the CCR5 receptor is described. The development of the medicinal chemistry strategy and SAR's which led to the identification of the piperidine amide compounds 33 and 36 as excellent leads for further evaluation is described, along with key physicochemical data which highlighted their lead potential.
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http://dx.doi.org/10.1016/j.bmcl.2009.01.012 | DOI Listing |
Acc Chem Res
January 2025
Department of Chemistry, University of California, Berkeley, California 94720, United States.
ConspectusThe electronic properties of atomically thin van der Waals (vdW) materials can be precisely manipulated by vertically stacking them with a controlled offset (for example, a rotational offset─i.e., twist─between the layers, or a small difference in lattice constant) to generate moiré superlattices.
View Article and Find Full Text PDFElife
January 2025
State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
Viral adhesion to host cells is a critical step in infection for many viruses, including monkeypox virus (MPXV). In MPXV, the H3 protein mediates viral adhesion through its interaction with heparan sulfate (HS), yet the structural details of this interaction have remained elusive. Using AI-based structural prediction tools and molecular dynamics (MD) simulations, we identified a novel, positively charged α-helical domain in H3 that is essential for HS binding.
View Article and Find Full Text PDFAm J Gastroenterol
January 2025
Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Beijing, China.
Objectives: Hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is one of the most common etiologies of acute pancreatitis (AP) worldwide. Compared to other etiologies, patients with HTG-AP may develop more severe AP, but previous studies yielded controversial conclusion due to the lack of adequate adjustment for the confounders. Therefore, this study aimed to examine the possibility and risk factors of developing severe AP in HTG-AP.
View Article and Find Full Text PDFIntroduction: Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
Department of Medicinal Chemistry, Institute of Pharmacy, Martin-Luther-University of Halle-Wittenberg, Halle (Saale) 06120, Germany.
Reliable in silico prediction of fragment binding modes remains a challenge in current drug design research. Due to their small size and generally low binding affinity, fragments can potentially interact with their target proteins in different ways. In the current study, we propose a workflow aimed at predicting favorable fragment binding sites and binding poses through multiple short molecular dynamics simulations.
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