Synthesis of 2-fluoro-11-hydroxy-N-propylnoraporphine: a potential dopamine D2 agonist.
[structure: see text]. 2-Fluoro-11-hydroxy-N-propylnoraporphine 4 (2-F-11-OH-NPa) was synthesized from thebaine in 13 steps with an overall yield of 1.35%. The key steps included the Pd-catalyzed 3-dehydroxylation of 14-hydroxymorphine, S(N)2 substitution of Ts(-) by F(-), and CH(3)SO(2)OH-promoted rearrangement of the substituted morphinandiene. The dopamine binding affinity of this compound was also investigated on rat brain membranes, and as expected, this compound displayed high affinity and selectivity at the D(2) receptor.
Zhang
Ao
A
Medicinal Chemistry Laboratory, Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA.
Csutoras
Csaba
C
Zong
Rushi
R
Neumeyer
John L
JL
D000818:Animals; D001060:Aporphines / Q000138:chemical synthesis*; D001921:Brain / Q000166:cytology / Q000187:drug effects; D018491:Dopamine Agonists / Q000138:chemical synthesis*; D010165:Palladium / Q000737:chemistry*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013797:Thebaine / Q000737:chemistry
C509885:2-fluoro-11-hydroxy-N-propylnoraporphine; D001060:Aporphines; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D013797:Thebaine; D010165:Palladium