title: Synthesis and binding studies of 2-arylapomorphines.
abstract: From codeine, four different 2-aryl substituted apomorphines were synthesised in 6 steps each. Oxidation of codeine with IBX followed by acid catalysed rearrangement gave morphothebaine, which was selectively triflylated at the 2-position and subsequently O-acetylated at the 11-position. The resulting triflate was coupled in a Suzuki-Miyaura type reaction with a series of 4-substituted arylboronic esters which, after deprotection, gave the desired 2-aryl apomorphines. The analogues were tested for affinity towards a range of dopaminergic, serotonergic and adrenergic receptors. 2-(4-Hydroxyphenyl)-apomorphine exhibited high affinity for the dopamine D2 receptor. A putative ligand-receptor interaction was put forward.
authors.affiliation: The Danish University of Pharmaceutical Sciences, Department of Medicinal Chemistry, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
authors.forename: Kåre
authors.initials: K
authors.lastname: Søndergaard
authors.forename: Jesper Langgaard
authors.initials: JL
authors.lastname: Kristensen
authors.forename: Mikael
authors.initials: M
authors.lastname: Palner
authors.forename: Nic
authors.initials: N
authors.lastname: Gillings
authors.forename: Gitte Moos
authors.initials: GM
authors.lastname: Knudsen
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.forename: Mikael
authors.initials: M
authors.lastname: Begtrup
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017982:Receptors, Biogenic Amine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D008024:Ligands; D017982:Receptors, Biogenic Amine; D017448:Receptors, Dopamine D2; D001058:Apomorphine