Evaluation of endo- and exo-aryl-substitutions and central scaffold modifications on diphenyl substituted alkanes as 5-lipoxygenase activating protein inhibitors

Bioorg Med Chem Lett. 2012 Jun 15;22(12):4133-8. doi: 10.1016/j.bmcl.2012.04.064. Epub 2012 Apr 20.

Abstract

A search for a suitable replacement for the central norbornyl scaffold presented in the recently disclosed novel FLAP inhibitors is herein described, as well as the SAR study performed on the endo and exo-aryl groups.

MeSH terms

  • 5-Lipoxygenase-Activating Protein Inhibitors / chemical synthesis*
  • 5-Lipoxygenase-Activating Protein Inhibitors / pharmacokinetics
  • 5-Lipoxygenase-Activating Protein Inhibitors / pharmacology
  • 5-Lipoxygenase-Activating Proteins / chemistry*
  • 5-Lipoxygenase-Activating Proteins / metabolism
  • Alkanes / chemical synthesis*
  • Alkanes / pharmacokinetics
  • Alkanes / pharmacology
  • Animals
  • Anti-Allergic Agents / chemical synthesis*
  • Anti-Allergic Agents / pharmacokinetics
  • Anti-Allergic Agents / pharmacology
  • Benzene Derivatives / chemical synthesis*
  • Benzene Derivatives / pharmacokinetics
  • Benzene Derivatives / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Injections, Intravenous
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 5-Lipoxygenase-Activating Protein Inhibitors
  • 5-Lipoxygenase-Activating Proteins
  • ALOX5AP protein, human
  • Alkanes
  • Anti-Allergic Agents
  • Benzene Derivatives