D-1 agonist and/or D-2 antagonist dopamine receptor properties of a seriesof ergoline derivatives: a structure-activity study

A series of (3,5-dioxopiperazin-1-yl)ergoline derivatives has been synthesi sed and evaluated in vitro and in vivo for their dopaminergic D-1 and D-2 c omponents. The structural contributions to the pharmacological profile of t he ergoline skeleton, its substituents on positions 1, 2, 6, 9, and the 3,5 -dioxopiperazin-1-yl portion of the molecule were examined. Structure-activ ity relationships within this series suggested that substitution on the erg oline skeleton in position 1 or 2 and on the 3,5-dioxopiperazin-4-nitrogen generated compounds with a spectrum of dopamine agonistic/antagonistic acti vity sensitive to both the nature and position of substituents. (C) Elsevie r, Paris.