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Synthesis and binding studies of 2-arylapomorphines
Kåre Søndergaard1, Jesper Langgaard Kristensen, Mikael Palner
1The Danish University of Pharmaceutical Sciences, Department of Medicinal Chemistry, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
Organic & Biomolecular Chemistry
|November 4, 2005
Summary
Researchers synthesized novel 2-aryl apomorphines from codeine. The compound 2-(4-Hydroxyphenyl)-apomorphine showed high affinity for the dopamine D2 receptor, suggesting potential therapeutic applications.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Pharmacology
Background:
- Apomorphine derivatives are known to interact with various neurotransmitter receptors.
- Developing novel ligands for dopaminergic receptors is crucial for treating neurological disorders.
Purpose of the Study:
- To synthesize a library of 2-aryl substituted apomorphines.
- To evaluate the receptor binding affinities of the synthesized analogues.
Main Methods:
- Multi-step synthesis starting from codeine.
- Utilized oxidation, acid-catalyzed rearrangement, selective triflation, O-acetylation, Suzuki-Miyaura coupling, and deprotection.
- Receptor binding assays for dopaminergic, serotonergic, and adrenergic receptors.
Main Results:
- Successfully synthesized four novel 2-aryl apomorphines in six steps each.
- 2-(4-Hydroxyphenyl)-apomorphine demonstrated significant affinity for the dopamine D2 receptor.
- Initial structure-activity relationship insights were gained.
Conclusions:
- The synthetic route provides access to diverse 2-aryl apomorphine analogues.
- 2-(4-Hydroxyphenyl)-apomorphine is a promising candidate for targeting the dopamine D2 receptor.
- Further investigation into ligand-receptor interactions is warranted.