Identification of BACE-1 inhibitors through directed C(sp3)-H activation on 5-oxo-pyrrolidine-3-carboxylic acid derivatives.
Org Biomol Chem
; 22(14): 2754-2763, 2024 Apr 03.
Article
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| ID: mdl-38488214
ABSTRACT
Convenient synthesis of stereochemically dense 5-oxo-pyrrolidines was obtained from succinic anyhdride and imines by combining the Castagnoli-Cushman reaction with directed Pd-catalyzed C(sp3)-H functionalization, taking advantage of the developing carboxylic group properly derivatized with 8-aminoquinoline as a directing group. These fully substituted 5-oxopyrrolidines were found to be able to inhibit BACE-1 enzyme with sub-micromolar activity, thanks to the interaction of the key aryl appendage introduced by C(sp3)-H activation within BACE-1 S2' subsite.
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MEDLINE
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En
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Org Biomol Chem
Asunto de la revista:
BIOQUIMICA
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QUIMICA
Año:
2024
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Article
País de afiliación:
Italia