کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1369632 | 981784 | 2012 | 5 صفحه PDF | دانلود رایگان |
A library of 1,3-disubstituted 2-propanols was synthesized and evaluated as low molecular weight probes for β-secretase inhibition. By screening a library of 121 1,3-disubstituted 2-propanol derivatives, we identified few compounds inhibiting the enzyme at low micromolar concentrations. The initial hits were optimized to yield a potent BACE-1 inhibitor exhibiting an IC50 constant in the nanomolar range. Exploration of the pharmacological properties revealed that these small molecular inhibitors possessed a high selectivity over cathepsin D and desirable physicochemical properties beneficial to cross the blood–brain barrier.
A library of 1,3-disubstituted 2-propanols was synthesized and tested as BACE-1 inhibitors. The compound with best activity was subjected to SAR studies to develop a nanomolar inhibitor with excellent selectivity over cathepsin D and predicted physicochemical properties optimal to penetrate BBB.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 14, 15 July 2012, Pages 4740–4744