Hydroxamic Acids Immobilized on Resins (HAIRs): Synthesis of Dual‐Targeting HDAC Inhibitors and HDAC Degraders (PROTACs)
Abstract: Inhibition of more than one cancer‐related pathway by multi‐target agents is an emerging approach in modern anticancer drug discovery. Here, based on the well‐established synergy between histone deacetylase inhibitors (HDACi) and alkylating agents, we present the discovery of a series of alkylating HDACi using a pharmacophore‐linking strategy. For the parallel synthesis of the target compounds, we developed an efficient solid‐phase‐supported protocol using hydroxamic acids immobilized on resins (HAIRs) as stable and versatile building blocks for the preparation of functionalized HDACi. The most promising compound, 3 n, was significantly more active in apoptosis induction, activation of caspase 3/7, and formation of DNA damage (γ‐H2AX) than the sum of the activities of either active principle alone. Furthermore, to demonstrate the utility of our preloaded resins, the HAIR approach was successfully extended to the synthesis of a proof‐of‐concept proteolysis‐targeting chimera (PROTAC), which efficiently degrades histone deacetylases.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Hydroxamic Acids Immobilized on Resins (HAIRs): Synthesis of Dual‐Targeting HDAC Inhibitors and HDAC Degraders (PROTACs) ; volume:59 ; number:50 ; year:2020 ; pages:22494-22499 ; extent:6
Angewandte Chemie / International edition. International edition ; 59, Heft 50 (2020), 22494-22499 (gesamt 6)
- Urheber
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Sinatra, Laura
Bandolik, Jan Josef
Roatsch, Martin
Sönnichsen, Melf
Schoeder, Clara T.
Hamacher, Alexandra
Schöler, Andrea
Borkhardt, Arndt
Meiler, Jens
Bhatia, Sanil
Kassack, Matthias U.
Hansen, Finn Kristian
- DOI
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10.1002/anie.202006725
- URN
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urn:nbn:de:101:1-2022061412384873743616
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:23 MESZ
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Beteiligte
- Sinatra, Laura
- Bandolik, Jan Josef
- Roatsch, Martin
- Sönnichsen, Melf
- Schoeder, Clara T.
- Hamacher, Alexandra
- Schöler, Andrea
- Borkhardt, Arndt
- Meiler, Jens
- Bhatia, Sanil
- Kassack, Matthias U.
- Hansen, Finn Kristian
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