Substituted 5-amino-4,5,6,7-tetrahydroindazoles as partial ergoline structures with dopaminergic activity.
Two series of tetrahydroindazoles were synthesized and evaluated for dopaminergic activity. A number of these partial ergoline analogues possess substituents that could mimic the C-8 substituent of the dopaminergic ergolines. Of the unsymmetrically substituted amine series 7a-k, the (monopropylamino)tetrahydroindazole 7b was most interesting as it was found to selectively activate the dopamine (DA) autoreceptor at a dose of 5 mg/kg in rats. The disubstituted amines 7g-k had significant DA postsynaptic activity as measured by increases of serum corticosterone levels in rats. The 6-substituted-5-aminotetrahydroindazoles 10a-d were found to possess only marginal dopaminergic activity.
McQuaid
L A
LA
Lilly Research Laboratory, Eli Lilly and Company, Indianapolis, Indiana 46285.
Latz
J E
JE
Clemens
J A
JA
Fuller
R W
RW
Wong
D T
DT
Mason
N R
NR
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004873:Ergolines / Q000138:chemical synthesis* / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis*; D051381:Rats; D013329:Structure-Activity Relationship
D015259:Dopamine Agents; D004873:Ergolines; D007191:Indazoles; D011720:Pyrazoles; D015102:3,4-Dihydroxyphenylacetic Acid; D011388:Prolactin; D004298:Dopamine; D006719:Homovanillic Acid