Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity.

Abstract A series of compounds possessing both H 1 histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H 1 -binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N -hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observed in vivo, as was increased CYP3A4 inhibition compared to their respective single-function drugs. Selected analogs in the series were shown to be orally active in guinea pig models.