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Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: prime side chromane-containing inhibitors.

Abstract：

:The structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the P1' region provided selectivity over Cat-D with a series of 2,2-dioxo-isothiochromanes and optimization of the P2' substituent of chromane-HEA(s) with polar substituents provided improvements in the compound's in vitro permeability. Significant potency gains were observed with small aliphatic substituents such as methyl, n-propyl, and cyclopropyl when placed at the C-2 position of the chromane.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Ng RA,Sun M,Bowers S,Hom RK,Probst GD,John V,Fang LY,Maillard M,Gailunas A,Brogley L,Neitz RJ,Tung JS,Pleiss MA,Konradi AW,Sham HL,Dappen MS,Adler M,Yao N,Zmolek W,Nakamura D,Quinn KP,Sauer JM,Bova MP,Ruslim

doi

10.1016/j.bmcl.2013.06.006

subject

Has Abstract

pub_date

2013-08-15 00:00:00

pages

4674-9

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00715-4

journal_volume

23

pub_type

杂志文章

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