Selective chiral inhibitors of 5-lipoxygenase with anti-inflammatory activity.
The studies described here, using enantiomers of an optically-active methoxy alkyl thiazole ICI216800 (1-methoxy-6-(naphth-2-yl-methoxyl)-1- (thiazol-2-yl)indane), provide unequivocal evidence for a specific, chiral interaction with 5-lipoxygenase. In accordance with their biochemical efficacy these compounds also demonstrate enantio-specific anti-inflammatory activity in a leukotriene-mediated model of inflammation. This is the first class of compounds for which 5-lipoxygenase inhibition and anti-inflammatory activity have been shown to be mediated via a specific chiral interaction.
McMillan
R M
RM
Bioscience 1, ICI Pharmaceuticals, Macclesfield, Cheshire.
Girodeau
J M
JM
Foster
S J
SJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015777:Eicosanoids / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D011817:Rabbits; D051381:Rats; D013237:Stereoisomerism; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D007189:Indans; D016859:Lipoxygenase Inhibitors; D013844:Thiazoles; C067841:1-methoxy-6-(naphth-2-yl-methoxy)-1-(thiazol-2-yl)indan; D007975:Leukotriene B4