Discovery and characterization of benzyloxy piperidine based dopamine 4 receptor antagonists
| Autor: | Anish K. Vadukoot, Viktoriya Mashinson, Kirsten Tolentino, Corey R. Hopkins |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Parkinson's disease
Clinical Biochemistry Pharmaceutical Science Biochemistry Article chemistry.chemical_compound Structure-Activity Relationship Piperidines In vivo Dopamine Drug Discovery medicine Humans Receptor Molecular Biology Dose-Response Relationship Drug Molecular Structure Organic Chemistry Receptors Dopamine D4 medicine.disease In vitro chemistry Dopamine receptor Molecular Medicine Dopamine Antagonists Piperidine Neuroscience medicine.drug |
| Zdroj: | Bioorg Med Chem Lett |
| ISSN: | 1464-3405 |
| Popis: | The dopamine receptor 4 (D4R) is highly expressed in both motor, associative and limbic subdivisions of the coritico-basal ganglia network. Due to the distribution in the brain, there is mounting evidence pointing to a role for the D4R in the modulation of this network and its subsequent involvement in L-DOPA induced dyskinesias in Parkinson’s disease. As part of our continued effort in the discovery of novel D4R antagonists, we report the discovery and characterization of a new 3- or 4-benzyloxypiperidine scaffold as D4R antagonists. We report several D4R selective compounds (>30-fold vs. other dopamine receptor subtypes) with improved in vitro and in vivo stability over previously reported D4R antagonists. |
| Databáze: | OpenAIRE |
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