Synthesis and dopamine antagonist activity of 2-thioether derivatives of the ergoline ring system.
A series of 2-thioether derivatives of a number of clavine alkaloid (ergoline) ring systems have been synthesized and tested for dopamine antagonist activity. Of the compounds tested 2-(methylthio)-agroclavine (8,9-didehydro-6,8-dimethyl-2-(methylthio)ergoline) (6) was the most potent and had a profile of activity in animal models indicative of potential antipsychotic activity. The synthesis and biological activity of a number of metabolites of 6, including the 13-hydroxy derivative, are also reported.
Tupper
D E
DE
Lilly Research Centre Ltd., Eli Lilly and Co., Windlesham, Surrey, U.K.
Pullar
I A
IA
Clemens
J A
JA
Fairhurst
J
J
Risius
F C
FC
Timms
G H
GH
Wedley
S
S
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004285:Dogs; D018492:Dopamine Antagonists; D004873:Ergolines / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis* / Q000494:pharmacology
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D013440:Sulfides