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. The activities observed were compared to single-function drugs.
Lewis
Timothy A
TA
UCB Research, 840 Memorial Dr, Cambridge MA 02139, USA. timothy.lewis@ucb-group.com
Bayless
Lynn
L
Eckman
Joseph B
JB
Ellis
James L
JL
Grewal
Gurmit
G
Libertine
Lyn
L
Marie Nicolas
Jean
J
Scannell
Ralph T
RT
Wels
Bruce F
BF
Wenberg
Karen
K
Wypij
Donna M
DM
D000818:Animals; D018938:Caco-2 Cells; D006634:Histamine H1 Antagonists / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats
D006634:Histamine H1 Antagonists; D016859:Lipoxygenase Inhibitors