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.
Lewis
Timothy A
TA
UCB Research, 840 Memorial Dr., Cambridge, MA 02139, USA. timlewis1201@comcast.net
Bayless
Lynn
L
DiPesa
Alan J
AJ
Eckman
Joseph B
JB
Gillard
Michel
M
Libertine
Lyn
L
Scannell
Ralph T
RT
Wypij
Donna M
DM
Young
Michelle A
MA
D000818:Animals; D001769:Blood; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D011485:Protein Binding; D013329:Structure-Activity Relationship
D006634:Histamine H1 Antagonists; D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4