Synthesis and in vitro dopaminergic activity of (2-aminoethyl)-1-hydroxy-2-pyridone type dopamine analogs.
Two isoteric/isoelectronic dopamine analogs based of (2'-aminoethyl)-1-hydroxy-2-pyridone without having the COMT vulnerable m-hydroxy group were synthesized via ten synthetic steps. Their dopaminergic activities were evaluated by measuring the inhibitory effects of prolactin secretion from the anterior pituitary in rats. The compounds 1 and 2 caused a reduction of prolactin secretion at the 10(-6) M concentration. Semiempirical MO calculations (at the AM-1 level) were performed on 1 and 2 in order to understand the structural and electronic features as compared to dopamine.
Yoon
S H
SH
Center for Drug Discovery, College of Pharmacy, University of Florida, Gainesville 32610.
Bodor
N S
NS
Simpkins
J W
JW
D000818:Animals; D004298:Dopamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats
D015259:Dopamine Agents; D011388:Prolactin; D004298:Dopamine