New antihistamines: Substituted piperazine and piperidine derivatives as novel H1-antagonists

Article abstract of DOI:10.1021/jm00020a018

Structural manipulation of polycyclic piperazinyl imide serotonergic agents led to the synthesis of compound 8, 2-[4-[4-[bis(4- fluorophenyl)methyl]-1-piperazinyl]butyl]-4,4a,5,5a,6,6a-hexa-hydro-4,6- ethenocycloprop[f]isoindole-1,3(2H,3aH)-dione, which demonstrated good H₁- antagonist activity. Substitution of a xanthinyl moiety for the polycyclic imide group led to the identification of novel xanthinyl-substituted piperazinyl and piperidinyl derivatives with potent antihistamine H₁- activity without the undesirable antidopaminergic activity of 8. One compound, 24, 7-[3-[4-(diphenylmethoxy)-1-piperidinyl]propyl]-3,7-dihydro- 1,3-dimethyl-1H-pyrine-2,6-dione (WY-49051), is a potent, orally active H₁- antagonist with a long duration of action and a favorable central nervous system profile.