NEW ANTIHISTAMINES - SUBSTITUTED PIPERAZINE AND PIPERIDINE-DERIVATIVES AS NOVEL H-1-ANTAGONISTS

Structural manipulation of polycyclic piperazinyl imide serotonergic a gents led to the synthesis of compound 4,6-ethenocycloprop[f]isoindole -1,3(2H,3aH)-dione, which demonstrated good H-1-antagonist activity. S ubstitution of a xanthinyl moiety for the polycyclic imide group led t o the identification of novel xanthinyl-substituted piperazinyl and pi peridinyl derivatives with potent antihistamine H-1-activity without t he undesirable antidopaminergic activity of 8. One compound, 24, opyl] -3,7-dihydro-1,3-dimethyl-1H-pyrine-2,6-dione (WY-49051), is a potent, orally active H-1-antagonist with a long duration of action and a fav orable central nervous system profile.