کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1369103 | 981746 | 2015 | 6 صفحه PDF | دانلود رایگان |
A series of azacyclic compounds substituted with isoxazole and 5-substituted isoxazolines were synthesized as acyclic modifications of the oxime class M1 mACh receptor agonist. Among them, 3-(tetrahydropyrin-3-yl)-5-(2-pyrrolodin-1-yl)isoxazoline compound 4f displayed potent and selective M1 mACh receptor agonist activity in the functional calcium mobilization assay (EC50 = 31 nM). Introduction of 2-pyrrolidinone and 3-tetrahydropyridine groups are pivotal to the high potency. Moreover, 4f was found to facilitate non-amyloidogenic amyloid precursor protein (APP) processing by significantly increasing ERK1/2 phosphorylation and sAPPα secretion, known disease-modifying effects related to M1 mAChR agonists in Alzheimer’s disease (AD).
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 25, Issue 7, 1 April 2015, Pages 1546–1551