A series of analogs containing tetrahydrothieno[3,2-c]pyridine-2-carboxamide as a building block with numerous alicyclic and aromatic amines were synthesized. All analogs were characterized by spectral analysis and evaluated for their in vitro antiplatelet activity. 4-Fluorophenyl amide derivatives (compounds 8-11) have been found to be most active in the series with respect to prasugrel and aspirin, a third generation antiplatelet agents (P2Y12 receptor antagonists). Docking study also manifested the admirable binding mode of in vitro active compounds 10 and 11 with the target protein. The results may provide a new perception for future pharmacophore with simple design strategy and avoid tedious synthesis of clopidogrel and prasugrel.
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http://dx.doi.org/10.1002/cbdv.201800550 | DOI Listing |
Am J Physiol Cell Physiol
January 2025
Department of Pharmaceutical Sciences, School of Pharmacy, College of Health and Human Sciences, North Dakota State University, Fargo, ND, USA.
Intra-abdominal sepsis is a life-threatening complex syndrome caused by microbes in the gut microbiota invading the peritoneal cavity. It is one of the major complications of intra-abdominal surgery. To date, only supportive therapies are available.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Neuroscience, Center for Brain Immunology and Glia, University of Virginia School of Medicine, Charlottesville, VA, USA.
Microglia and the border-associated macrophages contribute to the modulation of cerebral blood flow, but the mechanisms have remained uncertain. Here, we show that microglia regulate the cerebral blood flow baseline and the responses to whisker stimulation or intra-cisternal magna injection of adenosine triphosphate, but not intra-cisternal magna injection of adenosine in mice model. Notably, microglia repopulation corrects these cerebral blood flow anomalies.
View Article and Find Full Text PDFEur J Intern Med
January 2025
Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
For almost two decades, dual antiplatelet therapy (DAPT) has been considered the cornerstone of pharmacological treatment in patients undergoing percutaneous coronary intervention (PCI). DAPT composition and duration have considerably evolved in the last decade moving from fixed treatment durations to tailored strategies based on the individual ischemic and bleeding risks. The increasing awareness of the prognostic relevance of bleeding events after PCI and the need for tailoring DAPT according to the individual bleeding and ischemic risks paved the way to newer DAPT modulation strategies by early aspirin withdrawal which have been shown to decrease bleeding without affecting therapeutic efficacy.
View Article and Find Full Text PDFClin Transl Sci
January 2025
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
In neurovascular settings, including treatment and prevention of ischemic stroke and prevention of thromboembolic complications after percutaneous neurointerventional procedures, dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is the standard of care. Clopidogrel remains the most commonly prescribed P2Y12 inhibitor for neurovascular indications. However, patients carrying CYP2C19 no-function alleles have diminished capacity for inhibition of platelet reactivity due to reduced formation of clopidogrel's active metabolite.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, Yunnan, China. Electronic address:
Most Kunitz inhibitors exhibit serine protease inhibitory activity, but limited information is available on the regulation of platelet function. Herein, we report the purification and characterization of a novel single Kunitz domain inhibitor (Sibanin) from the salivary glands of the black fly Simulium bannaense. Recombinant Sibanin prolonged activated partial thromboplastin time and prothrombin time, and exhibited high-affinity binding to FXa and elastase with a KD of 5.
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