Halogenated boldine derivatives with enhanced monoamine receptor selectivity.
(S)-(+)-Boldine (1) was brominated, chlorinated, and iodinated using molecular bromine in acetic acid or N-halosuccinimides in trifluoroacetic acid. Initial halogenation occurs at C-3, followed (in the cases of chlorine and bromine) by the less reactive C-8, to afford 3-haloboldines- and 3,8-dihaloboldines (2-5). Using a 2:1 ratio of N-iodosuccinimide to boldine, however, only the 3-iodo derivative 6 was obtained. Radioligand binding studies of these products showed that halogenation of boldine at C-3 favors affinity for D(1)- (vs D(2)-) dopaminergic receptors, attaining a low nanomolar IC(50) value in the case of 3-iodoboldine (6).
Sobarzo-Sánchez
E M
EM
Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
Arbaoui
J
J
Protais
P
P
Cassels
B K
BK
D000085:Acetates; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001060:Aporphines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017982:Receptors, Biogenic Amine / Q000037:antagonists & inhibitors*; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects
D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001060:Aporphines; D001552:Benzazepines; D002712:Chlorides; D017982:Receptors, Biogenic Amine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D020891:Raclopride; C011686:boldine