We describe herein the discovery and development of a series of 4-arylthieno[3,2-d]pyrimidines which are potent adenosine A(2A) receptor antagonists. These novel compounds show high degrees of selectivity against the human A(1), A(2B) and A(3) receptor sub-types. Moreover, a number of these compounds show promising activity in vivo, suggesting potential utility in the treatment of Parkinson's disease.
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http://dx.doi.org/10.1016/j.bmcl.2008.03.076 | DOI Listing |
CNS Neurol Disord Drug Targets
January 2025
Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, India.
Parkinson's disease (PD) is a progressive neurological condition characterized by both dopaminergic and non-dopaminergic brain cell loss. Patients with Parkinson's disease have tremors as a result of both motor and non-motor symptoms developing. Idiopathic Parkinson's disease (idiopathic PD) prevalence is increasing in people over 60.
View Article and Find Full Text PDFJ Lipid Res
January 2025
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:
Dysfunctional cholesterol metabolism is highly prevalent in patients with hyperuricemia. Both uric acid and cholesterol are independent risk factors for atherosclerosis, contributing to an increased incidence of cardiovascular disease in hyperuricemia. Investigating the pathological mechanisms underlying cholesterol metabolism dysfunction in hyperuricemia is essential.
View Article and Find Full Text PDFImmunol Rev
March 2025
Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Since their first description in 2008, T-bet+ B cells have emerged as a clinically important B cell subset. Now commonly known as ABCs (Age-associated B Cells), they are uniquely characterized by their expression of the transcription factor T-bet. Indeed, this singular factor defines this B cell subset.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal; CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal. Electronic address:
The adenosine A receptor (AR), a class A GPCR, is a known player in neurological diseases, including Parkinson's disease and Alzheimer's disease, and is also implicated in SARS-CoV-2 infection. Recent studies have revealed its oligomerization with metabotropic glutamate receptor type 5 (mGluR), a class C G protein coupled receptor (GPCR) that exists in the homodimeric form. Simultaneous activation of both receptors synergistically enhances mGluR-mediated effects in the hippocampus.
View Article and Find Full Text PDFHeliyon
January 2025
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Compelling evidence has demonstrated that rehabilitation through physical exercise, a non-invasive and non-surgical intervention, enhances muscle reinnervation and motor recovery after peripheral nerve injury (PNI) by increasing muscle-derived brain-derived neurotrophic factor (BDNF) expression and triggering TrkB-dependent axonal plasticity. Adenosine has been widely acknowledged to trigger TrkB via A2A receptor (A2AR). Since motor nerve terminals co-express TrkBs and A2ARs and depolarizing conditions increase muscle release of BDNF and adenosine, we examined whether A2ARs activation could recapitulate the functional recovery benefits of intermittent exercise after a nerve crush.
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