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.

Synthesis of morpholine derivatives using the Castagnoli-Cushman reaction as BACE1 inhibitors: Unexpected binding activity of cyclic thioamides / Calugi L.; Lenci E.; Innocenti R.; Trabocchi A.. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - ELETTRONICO. - 30(2020), pp. 127211-127211. [10.1016/j.bmcl.2020.127211]

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

Calugi L.;Lenci E.;Innocenti R.;Trabocchi A.
2020

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.
30
127211
127211
Goal 3: Good health and well-being
Calugi L.; Lenci E.; Innocenti R.; Trabocchi A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1193267
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