Substituted indoles as potent and orally active 5-lipoxygenase activating protein (FLAP) inhibitors.
Journal Article (Journal Article)
This paper reports on the SAR investigation of inhibitors of 5-lipoxygenase activating protein (FLAP) based on MK-0591. Emphasis was made on modifications to the nature of the link between the indole and the quinoline moieties, to the substitution pattern around the two heterocycles and to possible replacements of the quinoline moiety. Lead optimization culminated in (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(pyridin-2-ylmethoxy)-ind ol-2-yl]-2,2-dimethylpropanoic acid (18k), as a potent inhibitor of leukotriene biosynthesis that is well absorbed and active in functional models.
Full Text
Duke Authors
Cited Authors
- Frenette, R; Hutchinson, JH; Léger, S; Thérien, M; Brideau, C; Chan, CC; Charleson, S; Ethier, D; Guay, J; Jones, TR; McAuliffe, M; Piechuta, H; Riendeau, D; Tagari, P; Girard, Y
Published Date
- August 1999
Published In
Volume / Issue
- 9 / 16
Start / End Page
- 2391 - 2396
PubMed ID
- 10476875
Electronic International Standard Serial Number (EISSN)
- 1464-3405
International Standard Serial Number (ISSN)
- 0960-894X
Digital Object Identifier (DOI)
- 10.1016/s0960-894x(99)00399-6
Language
- eng