Scaffold Hopping from Amodiaquine to Novel Nurr1 Agonist Chemotypes via Microscale Analogue Libraries
Abstract: Several lines of evidence suggest the ligand‐sensing transcription factor Nurr1 as a promising target to treat neurodegenerative diseases. Nurr1 modulators to validate and exploit this therapeutic potential are rare, however. To identify novel Nurr1 agonist chemotypes, we have employed the Nurr1 activator amodiaquine as template for microscale analogue library synthesis. The first set of analogues was based on the 7‐chloroquiolin‐4‐amine core fragment of amodiaquine and revealed superior N‐substituents compared to diethylaminomethylphenol contained in the template. A second library of analogues was subsequently prepared to replace the chloroquinolineamine scaffold. The two sets of analogues enabled a full scaffold hop from amodiaquine to a novel Nurr1 agonist sharing no structural features with the lead but comprising superior potency on Nurr1. Additionally, pharmacophore modeling based on the entire set of active and inactive analogues suggested key features for Nurr1 agonists.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Scaffold Hopping from Amodiaquine to Novel Nurr1 Agonist Chemotypes via Microscale Analogue Libraries ; day:21 ; month:02 ; year:2022 ; extent:1
ChemMedChem ; (21.02.2022) (gesamt 1)
- Creator
- DOI
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10.1002/cmdc.202200026
- URN
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urn:nbn:de:101:1-2022022214133073480728
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:35 AM CEST
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Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Willems, Sabine
- Müller, Marcel
- Ohrndorf, Julia
- Heering, Jan
- Proschak, Ewgenij
- Merk, Daniel
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Scaffold hopping from amodiaquine to novel Nurr1 agonist chemotypes via microscale analogue libraries
Development of Nurr1 agonists from amodiaquine by scaffold hopping and fragment growing
Scaffold hopping in medicinal chemistry
Deep scaffold hopping with multimodal transformer neural networks
In silico work flow for scaffold hopping in Leishmania
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Polymeric fibrous scaffold on macro/microscale towards tissue regeneration
Ligand scaffold hopping combining 3D maximal substructure search and molecular similarity
Scaffold hopping from natural products to synthetic mimetics by holistic molecular similarity
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ScaffoldGVAE: scaffold generation and hopping of drug molecules via a variational autoencoder based on multi-view graph neural networks
Scaffold-Hopping-Strategie zur Entwicklung neuer kovalenter Januskinase 3 Inhibitoren mit hoher Isoform Selektivität
Scaffold hopping from amodiaquine to novel Nurr1 agonist chemotypes via microscale analogue libraries
Development of Nurr1 agonists from amodiaquine by scaffold hopping and fragment growing
Scaffold hopping in medicinal chemistry
Deep scaffold hopping with multimodal transformer neural networks
In silico work flow for scaffold hopping in Leishmania
Scaffold-Hopping from Synthetic Drugs by Holistic Molecular Representation
Polymeric fibrous scaffold on macro/microscale towards tissue regeneration
Ligand scaffold hopping combining 3D maximal substructure search and molecular similarity
Scaffold hopping from natural products to synthetic mimetics by holistic molecular similarity
Combining structural and bioactivity-based fingerprints improves prediction performance and scaffold hopping capability
ScaffoldGVAE: scaffold generation and hopping of drug molecules via a variational autoencoder based on multi-view graph neural networks