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2-Haloaporphines as potent dopamine agonists
S Ramsby1, J L Neumeyer, D Grigoriadis
1Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Massachusetts 02115.
Journal of Medicinal Chemistry
|June 1, 1989
Summary
Researchers synthesized novel aporphine derivatives, including 2-fluoroapomorphine, which showed higher dopamine D-2 receptor affinity than apomorphine. Structure-activity relationships were explored for these potential therapeutics.
Area of Science:
- Medicinal Chemistry
- Neuropharmacology
Background:
- Aporphines are a class of compounds with known biological activity.
- Dopamine D-2 receptors are critical targets in the central nervous system and anterior pituitary.
Purpose of the Study:
- To synthesize novel 2-amino- and 2-halo-substituted aporphines.
- To evaluate the binding affinity of these new compounds to the dopamine D-2 receptor.
- To elucidate structure-activity relationships for dopamine D-2 receptor ligands.
Main Methods:
- Synthesis of aporphine derivatives utilizing a Smiles rearrangement.
- Evaluation of receptor binding affinity using radioligand displacement assays.
- Analysis of structure-activity relationships against a proposed dopamine D-2 receptor model.
Main Results:
- Successful synthesis of 2-amino- and 2-halo-substituted aporphines.
- 2-Fluoroapomorphine demonstrated the highest potency, exhibiting 1.5 times greater affinity than (-)-apomorphine.
- Key structural features influencing dopamine D-2 receptor interaction were identified.
Conclusions:
- Novel aporphine derivatives were synthesized and characterized.
- 2-Fluoroapomorphine represents a potent dopamine D-2 receptor ligand.
- The findings provide valuable insights into the structure-activity relationships of aporphines at the dopamine D-2 receptor.
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