5-Lipoxygenase inhibition by N-hydroxycarbamates in dual-function compounds.

A series of N-hydroxycarbamates containing a histaminergic H(1) receptor antagonist pharmacophore was synthesized. In vitro assays determined the compounds had both histaminergic binding and 5-lipoxygenase inhibiting activities comparable to the corresponding N-hydroxyurea analog. Animal models demonstrated antihistaminergic and the 5-lipopxygenase inhibitory activity, with the N-hydroxyurea analog having a better overall profile.

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

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.

5-lipoxygenase inhibitors with histamine H(1) receptor antagonist activity.

A series of novel compounds with both 5-lipoxygenase (5-LO) inhibitory and histamine H(1) receptor antagonist activity were designed for the treatment of asthma. These dual-function compounds were made by connecting 5-LO and H(1) pharmacophores,N-hydroxyureas and benzhydryl piperazines, respectively. A range of in vitro activities was observed, with the furan analog 10 demonstrating both activities in an animal model.