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Synthesis of morpholine derivatives using the Castagnoli-Cushman reaction as BACE1 inhibitors: Unexpected binding activity of cyclic thioamides.

Abstract：

:The Castagnoli-Cushman reaction between diglycolic anhydride and imines was applied for the synthesis of morpholine derivatives containing a thioamide or an amidino group. Enzyme inhibition assays towards BACE1 revealed an unexpected role of the cyclic thioamide group in providing inhibition in the micromolar range. Molecular docking calculations showed the thioamido group interacting with catalytic aspartic acid, and calculated BBB permeability indicated this molecular scaffold as a promising hit for further optimization.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Calugi L,Lenci E,Innocenti R,Trabocchi A

doi

10.1016/j.bmcl.2020.127211

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

127211

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(20)30311-5

journal_volume

30

pub_type

杂志文章

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