Hobson, Adrian D. published the artcileDiscovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P5) Agonist for the Potential Treatment of Neurodegenerative Disorders, Application of 4-(4-Chlorophenoxy)benzaldehyde, the main research area is sphingosine phosphate receptor agonist neurodegenerative disorder.
S1P5 is one of 5 receptors for sphingosine-1-phosphate and is highly expressed on endothelial cells within the blood-brain barrier, where it maintains barrier integrity in in vitro models. Little more is known about the effects of S1P5 modulation due to the absence of tool mols. with suitable selectivity and drug-like properties. We recently reported that mol. A-971432 (Harris, 2010) (29 in this paper) is highly efficacious in reversing lipid accumulation and age-related cognitive decline in rats. Herein we describe the development of a series of selective S1P5 agonists that led to the identification of compound 29, which is highly selective for S1P5 and has excellent plasma and CNS exposure after oral dosing in preclin. species. To further support its suitability for in vivo studies of S1P5 biol., we extensively characterized 29, including confirmation of its selectivity in pharmacodynamic assays of S1P1 and S1P3 function in rats. In addition, we found that 29 improves blood-brain barrier integrity in an in vitro model and reverses age-related cognitive decline in mice. These results suggest that S1P5 agonism is an innovative approach with potential benefit in neurodegenerative disorders involving lipid imbalance and/or compromised blood-brain barrier such as Alzheimer’s disease or multiple sclerosis.
Journal of Medicinal Chemistry published new progress about Alzheimer disease. 61343-99-5 belongs to class chlorides-buliding-blocks, name is 4-(4-Chlorophenoxy)benzaldehyde, and the molecular formula is C13H9ClO2, Application of 4-(4-Chlorophenoxy)benzaldehyde.
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