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In this letter, we describe our efforts to design HEA BACE-1 inhibitors that are highly permeable coupled with negligible levels of permeability-glycoprotein activity. These efforts culminate in producing
16 which lowers Aβ by 28% and 32% in the cortex and CSF, respectively, in the
wild type preclinical Hartley guinea pig animal model when dosed orally at 30
mpk BID for 2.5
days.
In this Letter, we describe our efforts to design HEA BACE-1 inhibitors that are highly permeable coupled with negligible levels of permeability-glycoprotein activity. These efforts culminate in producing
16 which lowers Αβ by 28% and 32% in the cortex and CSF, respectively, in the preclinical
wild type Hartley guinea pig animal model when dosed orally at 30
mpk BID for 2.5
days.