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Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine transition state mimetics.

Abstract：

:Our first generation of hydroxyethylamine BACE-1 inhibitors proved unlikely to provide molecules that would lower amyloid in an animal model at low oral doses. This observation led us to the discovery of a second generation of inhibitors having nanomolar activity in a cell-based assay and with the potential for improved pharmacokinetic profiles. In this Letter, we describe our successful strategy for the optimization of oral bioavailability and also give insights into the design of compounds with the potential for improved brain penetration.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Charrier N,Clarke B,Cutler L,Demont E,Dingwall C,Dunsdon R,Hawkins J,Howes C,Hubbard J,Hussain I,Maile G,Matico R,Mosley J,Naylor A,O'Brien A,Redshaw S,Rowland P,Soleil V,Smith KJ,Sweitzer S,Theobald P,Vesey D,

doi

10.1016/j.bmcl.2009.03.149

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

3674-8

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)00470-3

journal_volume

19

pub_type

杂志文章

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