We describe the design, synthesis and profiling of a novel series of PDE5 inhibitors. We take advantage of an alternate projection into the solvent region to identify compounds with excellent potency, selectivity and pharmacokinetic profiles.
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http://dx.doi.org/10.1016/j.bmcl.2011.08.106 | DOI Listing |
Nat Chem
January 2025
Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford, UK.
Understanding the dynamics of membrane protein-ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer.
View Article and Find Full Text PDFFood Addit Contam Part A Chem Anal Control Expo Risk Assess
January 2025
Shanxi Key Laboratory of Food and Drug Safety Prevention and Control, Inspection and Testing Center of Shanxi Province, Taiyuan, Shanxi, China.
Two novel phosphodiesterase 5 (PDE-5) inhibitors were detected in pressed candy using high-performance liquid chromatography (HPLC)-diode array detection. Following extraction with acetonitrile and sonication, the compounds were isolated and purified semi-preparative liquid chromatography. Structural characterisation was achieved through high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy.
View Article and Find Full Text PDFJ Comput Chem
January 2025
Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, New South Wales, Australia.
Phosphodiesterase 5 (PDE5) inhibitors have shown great potential in treating Alzheimer's disease by improving memory and cognitive function. In this study, we evaluated fluspirilene, a drug commonly used to treat schizophrenia, as a potential PDE5 inhibitor using computational methods. Molecular docking revealed that fluspirilene binds strongly to PDE5, supported by hydrophobic and aromatic interactions.
View Article and Find Full Text PDFChest
January 2025
Pulmonary Division, Lady Davis Carmel Medical Center, Faculty of Medicine Technion Institute of Technology, Haifa, Israel.
Am J Physiol Lung Cell Mol Physiol
January 2025
Department of Pharmacology and Toxicology. School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
Severe vitamin D (vitD) deficiency is a very common condition in patients with pulmonary arterial hypertension (PAH) and it is predictor of poor prognosis. There is emerging evidence suggesting a connection between the insufficient response to phosphodiesterase-5 inhibitors (PDE5i) and vitD deficiency in patients with PAH. In the present translational study, vitD deficiency was induced in Wistar rats by exposure to vitD free diet for 5 weeks and followed by Su5416 administration and hypoxia (10%) for 3 weeks, a standard experimental model of PAH.
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