3-Aminopyridazine derivatives with atypical antidepressant, serotonergic and dopaminergic activities
作者:Camille Georges Wermuth、Gilbert Schlewer、Jean Jacques Bourguignon、Georges Maghioros、Marie Jeanne Bouchet、Claudine Moire、Jean Paul Kan、Paul Worms、Kathleen Biziere
DOI:10.1021/jm00123a004
日期:1989.3
Minaprine [3-[(beta-morpholinoethyl)amino]-4-methyl-6-phenylpyridazine dihydrochloride] is active in most animal models of depression and exhibits in vivo a dual dopaminomimetic and serotoninomimetic activity profile. In an attempt to dissociate these two effects and to characterize the responsible structural requirements, a series of 47 diversely substituted analogues of minaprine were synthesized and tested for their potential antidepressant, serotonergic, and dopaminergic activities. The structure-activity relationships show that dopaminergic and serotonergic activities can be dissociated. Serotonergic activity appears to be correlated mainly with the substituent in the 4-position of the pyridazine ring whereas the dopaminergic activity appears to be dependent on the presence, or in the formation, of a para-hydroxylated aryl ring in the 6-position of the pyridazine ring.