Macrocyclic BACE-1 inhibitors acutely reduce Aβ in brain after po application
2010
Abstract 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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
19
References
48
Citations
NaN
KQI