کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1375361 | 981937 | 2010 | 5 صفحه PDF | دانلود رایگان |

A series of macrocyclic peptidic BACE-1 inhibitors was designed. While potency on BACE-1 was rather high, the first set of compounds showed poor brain permeation and high efflux in the MDRI–MDCK assay. The replacement of the secondary benzylamino group with a phenylcyclopropylamino group maintained potency on BACE-1, while P-glycoprotein-mediated efflux was significantly reduced and brain permeation improved. Several compounds from this series demonstrated acute reduction of Aβ in human APP-wildtype transgenic (APP51/16) mice after oral administration.
Starting from macrocyclic peptidic BACE-1 inhibitor 1, brain permeation was optimized for this series using a MDRI–MDCK assay to lead to NB-216 and analogues. These compounds show acute reduction of Aβ in brain of APP51/16 transgenic mice, after po application.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 2, 15 January 2010, Pages 603–607