Abstract
(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).
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetates
-
Animals
-
Anti-Inflammatory Agents, Non-Steroidal / chemistry*
-
Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
-
Aporphines / chemistry*
-
Aporphines / isolation & purification
-
Aporphines / pharmacology*
-
Benzazepines / pharmacology
-
Binding, Competitive / drug effects
-
Brain Chemistry / drug effects
-
Chlorides / chemistry
-
Neostriatum / drug effects
-
Neostriatum / metabolism
-
Raclopride / pharmacology
-
Radioligand Assay
-
Rats
-
Rats, Wistar
-
Receptors, Biogenic Amine / antagonists & inhibitors*
-
Receptors, Dopamine D1 / drug effects
-
Receptors, Dopamine D2 / drug effects
Substances
-
Acetates
-
Anti-Inflammatory Agents, Non-Steroidal
-
Aporphines
-
Benzazepines
-
Chlorides
-
Receptors, Biogenic Amine
-
Receptors, Dopamine D1
-
Receptors, Dopamine D2
-
Raclopride
-
boldine