Design, synthesis, and in vivo activity of novel inhibitors of delta-5 desaturase for the treatment of metabolic syndrome

Bioorg Med Chem Lett. 2015 Sep 15;25(18):3836-9. doi: 10.1016/j.bmcl.2015.07.066. Epub 2015 Jul 26.

Abstract

The synthesis, SAR, and in vivo activity of inhibitors of delta-5 desaturase are described. Ring-constraint of the initial series provided access to a variety of in vitro active chemotypes, from which the indazole was selected. Examples from the indazole series displayed in vivo activity in reducing the enzymatic activity of liver delta-5 desaturase.

Keywords: Delta-5 desaturase; In vivo efficacy; Indazole; Metabolic syndrome; Ring constraint.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Animals
  • Delta-5 Fatty Acid Desaturase
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fatty Acid Desaturases / antagonists & inhibitors*
  • Fatty Acid Desaturases / metabolism
  • Humans
  • Liver / enzymology
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / enzymology
  • Metabolic Syndrome / metabolism
  • Mice
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Amides
  • Delta-5 Fatty Acid Desaturase
  • Enzyme Inhibitors
  • Fatty Acid Desaturases