Structure and activity relationships leading to the discovery of ICI D2138, a selective, potent and orally active inhibitor of 5-lipoxygenase.
Structure and activity relationships of (methoxyalkyl)thiazole and 4-methoxytetrahydropyran series of 5-lipoxygenase inhibitors are reviewed. One member of the 4-methoxytetrahydropyran series, 6-([fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxy]methyl) -1- methylquinol-2-one (ICI D2138), is undergoing clinical evaluation.
Research Department 1, ICI Pharmaceuticals, Alderley Park, Macclesfield, UK.
G C
GC
Crawley
T G
TG
Bird
P
P
Bruneau
R I
RI
Dowell
P N
PN
Edwards
S J
SJ
Foster
J M
JM
Girodeau
R M
RM
McMillan
E R
ER
Walker
D
D
Waterson
D000284:Administration, Oral; D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D011714:Pyrans / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology
D016859:Lipoxygenase Inhibitors; D011714:Pyrans; D015363:Quinolones; D013844:Thiazoles; C075799:ICI D2138; D007975:Leukotriene B4