2. Academic Validation
  3. Discovery and characterization of benzyloxy piperidine based dopamine 4 receptor antagonists

Discovery and characterization of benzyloxy piperidine based dopamine 4 receptor antagonists

  • Bioorg Med Chem Lett. 2022 Apr 1;61:128615. doi: 10.1016/j.bmcl.2022.128615.
Kirsten T Tolentino 1,  Viktoriya Mashinson 1,  Anish K Vadukoot 1,  Corey R Hopkins 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
  • 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: [email protected].
PMID: 35151866 DOI: 10.1016/j.bmcl.2022.128615
Abstract

The Dopamine Receptor 4 (D4R) is highly expressed in both motor, associative and limbic subdivisions of the cortico-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.

Keywords

Antagonists; Benzyloxypiperidine; D4R; Dopamine 4 receptor; Parkinson’s disease.

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