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Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity
Timothy A Lewis1, Michelle A Young, Mark P Arrington
1UCB Research, 840 Memorial Drive, Cambridge, MA 02139, USA. timlewis1201@comcast.net
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.
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