title: Synthesis and SAR study of a novel series of dopamine receptor agonists.
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.
authors.affiliation: 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.
authors.forename: Rune
authors.initials: R
authors.lastname: Risgaard
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Jensen
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Jørgensen
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark.
authors.forename: Benny
authors.initials: B
authors.lastname: Bang-Andersen
authors.affiliation: Drug ADME Research, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark.
authors.forename: Claus T
authors.initials: CT
authors.lastname: Christoffersen
authors.affiliation: Drug ADME Research, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Jensen
authors.affiliation: Department of Drug Design and Pharmacology, The Faculty of Health and Medical Sciences, University of Copenhagen, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
authors.forename: Jesper L
authors.initials: JL
authors.lastname: Kristensen
authors.affiliation: Neuroscience Drug Discovery, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark. Electronic address: askp@lundbeck.com.
authors.forename: Ask
authors.initials: A
authors.lastname: Püschl
mesh_terms: D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine
keywords: Dopamine receptor agonist; Parkinson’s disease; Rotigotine