20037-36-9Relevant academic research and scientific papers
A Selective Prostaglandin E2 Receptor Subtype 2 (EP2) Antagonist Increases the Macrophage-Mediated Clearance of Amyloid-Beta Plaques
Fox, Brian M.,Beck, Hilary P.,Roveto, Philip M.,Kayser, Frank,Cheng, Qingwen,Dou, Hannah,Williamson, Toni,Treanor, James,Liu, Hantao,Jin, Lixia,Xu, Guifen,Ma, Ji,Wang, Songli,Olson, Steven H.
supporting information, p. 5256 - 5273 (2015/08/03)
A high-throughput screen resulted in the discovery of benzoxazepine 1, an EP2 antagonist possessing low microsomal stability and potent CYP3A4 inhibition. Modular optimization of lead compound 1 resulted in the discovery of benzoxazepine 52, a molecule with single-digit nM binding affinity for the EP2 receptor and significantly improved microsomal stability. It was devoid of CYP inhibition and was 4000-fold selective against the other EP receptors. Compound 52 was shown to have good PK properties in CD-1 mice and high CNS permeability in C57Bl/6s mice and Sprague-Dawley rats. In an ex vivo assay, it demonstrated the ability to increase the macrophage-mediated clearance of amyloid-beta plaques from brain slices in a dose-dependent manner.
