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Structure activity relationships of resorcinol substituted ring systems.
Archives Internationales De Pharmacodynamie Et De Therapie
|September 1, 1984
Summary
Resorcinol dopamine derivatives showed activity, particularly in aminotetralin and octahydrobenzo[f]quinoline systems. This activity mirrored catechol dopamine derivative patterns, unlike adrenoceptor activity.
Area of Science:
- Medicinal Chemistry
- Neuropharmacology
- Organic Synthesis
Background:
- Dopamine receptor agonists are crucial for treating various neurological disorders.
- Understanding structure-activity relationships (SAR) of dopamine receptor ligands is vital for drug development.
- Resorcinol derivatives offer an alternative to catechol-based dopamine analogs.
Purpose of the Study:
- To synthesize and evaluate resorcinol derivatives of various ring systems for dopamine receptor agonist activity.
- To compare the SAR of resorcinol derivatives with known catechol derivatives.
- To investigate the influence of ring system structure on dopamine receptor activity.
Main Methods:
- Synthesis of resorcinol derivatives based on dopamine, aminotetralin, indan, benzocycloheptane, octahydrobenzo(f)quinoline, and octahydrobenzo[g]quinoline scaffolds.
- In vitro binding assays to assess receptor affinity.
- In vivo studies including anesthetized cat blood pressure and heart rate, cat cardioaccelerator nerve preparation, and rat rotations following unilateral caudate nucleus denervation.
Main Results:
- Dopamine receptor agonist activity was predominantly observed in aminotetralin and octahydrobenzo[f]quinoline derivatives.
- The activity patterns of resorcinol derivatives closely resembled those of catechol derivatives, particularly concerning alpha- and beta-conformer specific binding.
- Ring systems inactive for catechol derivatives also showed inactivity for resorcinol derivatives.
- Structural requirements for dopamine receptor activity differed significantly from those for alpha- and beta-adrenoceptor activity.
Conclusions:
- Resorcinol substitution can yield dopamine receptor agonists with activity profiles similar to catechol analogs.
- The aminotetralin and octahydrobenzo[f]quinoline ring systems are favorable scaffolds for developing dopamine receptor active resorcinol derivatives.
- Distinct structural requirements exist for dopamine receptor and adrenoceptor agonist activity, highlighting the selectivity achievable through structural modification.