A Buchwald-Hartwig Protocol to Enable Rapid Linker Exploration of Cereblon E3-Ligase PROTACs*.

Autor: Hayhow TG; Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge, CB4 0WG, UK., Borrows REA; Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge, CB4 0WG, UK., Diène CR; Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge, CB4 0WG, UK., Fairley G; Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Macclesfield Campus, Etherow Building, Silk Road Industrial Estate, Macclesfield, SK10 2NA, UK., Fallan C; Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge, CB4 0WG, UK., Fillery SM; Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge, CB4 0WG, UK., Scott JS; Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge, CB4 0WG, UK., Watson DW; Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge, CB4 0WG, UK.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2020 Dec 15; Vol. 26 (70), pp. 16818-16823. Date of Electronic Publication: 2020 Nov 03.
DOI: 10.1002/chem.202003137
Abstrakt: A palladium-catalysed Buchwald-Hartwig amination for lenalidomide-derived aryl bromides was optimised using high throughput experimentation (HTE). The substrate scope of the optimised conditions was evaluated for a range of alkyl- and aryl- amines and functionalised aryl bromides. The methodology allows access to new cereblon-based bifunctional proteolysis targeting chimeras with a reduced step count and improved yields.
(© 2020 Wiley-VCH GmbH.)
Databáze: MEDLINE
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