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


  • eng