2. Academic Validation
  3. Synthesis and SAR study of a novel series of dopamine receptor agonists

Synthesis and SAR study of a novel series of dopamine receptor agonists

  • Bioorg Med Chem. 2014 Jan 1;22(1):381-92. doi: 10.1016/j.bmc.2013.11.012.
Rune Risgaard 1,  Martin Jensen 2,  Morten Jørgensen 2,  Benny Bang-Andersen 2,  Claus T Christoffersen 3,  Klaus G Jensen 3,  Jesper L Kristensen 4,  Ask Püschl 5
Affiliations

Affiliations

  • 1 Neuroscience Drug Discovery, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark; Department of Drug Design and Pharmacology, The Faculty of Health and Medical Sciences, University of Copenhagen, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
  • 2 Neuroscience Drug Discovery, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark.
  • 3 Drug ADME Research, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark.
  • 4 Department of Drug Design and Pharmacology, The Faculty of Health and Medical Sciences, University of Copenhagen, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
  • 5 Neuroscience Drug Discovery, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark. Electronic address: askp@lundbeck.com.
PMID: 24296012 DOI: 10.1016/j.bmc.2013.11.012
Abstract

The synthesis of a novel series of Dopamine Receptor agonists are described as well as their in vitro potency and efficacy on dopamine D₁ and D₂ receptors. This series was designed from pergolide and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinolin-6-ol (PHBQ) and resulted in the synthesis of (2R,4aR,10aR)-2-methylsulfanylmethyl-4-propyl-3,4,4a,5,10,10a-hexahydro-2H-naphtho[2,3-b][1,4]oxazin-9-ol (compound 27), which has a D₁ and D₂ receptor profile similar to that of the most recently approved drug for Parkinson's disease, rotigotine.

Keywords

Dopamine receptor agonist; Parkinson’s disease; Rotigotine.

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