Synthesis and binding studies of 2-arylapomorphines.
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.
Søndergaard
Kåre
K
The Danish University of Pharmaceutical Sciences, Department of Medicinal Chemistry, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
Kristensen
Jesper Langgaard
JL
Palner
Mikael
M
Gillings
Nic
N
Knudsen
Gitte Moos
GM
Roth
Bryan L
BL
Begtrup
Mikael
M
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
D008024:Ligands; D017982:Receptors, Biogenic Amine; D017448:Receptors, Dopamine D2; D001058:Apomorphine