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

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Lewis TA, Young MA, Arrington MP, Bayless L, Cai X, Collart P, Eckman JB, Ellis JL, Ene DG, Libertine L, Nicolas JM, Scannell RT, Wels BF, Wenberg K, Wypij DM

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

Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.

PubMed ID
15482930 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CetirizineHistamine H1 receptorKi (nM)14N/AN/ADetails
DesloratadineHistamine H1 receptorKi (nM)0.97N/AN/ADetails
LoratadineHistamine H1 receptorKi (nM)414N/AN/ADetails
ZileutonArachidonate 5-lipoxygenaseIC 50 (nM)873N/AN/ADetails