Tetrahydrobenzothiophene carboxamides: Beyond the kinase domain and into the fatty acid realm

Bioorg Med Chem Lett. 2017 Sep 15;27(18):4462-4466. doi: 10.1016/j.bmcl.2017.08.006. Epub 2017 Aug 5.

Abstract

A series of tetrahydrobenzothiophene carboxamides, inspired by structural features present in kinase and SCD1 inhibitors, are presented here. Prototype compound 8 (MMDD13) modulates fatty acid elongase and desaturase indexes, lipid accumulation, while preserving kinase inhibitory activity. This chemotype represents a stepping stone towards chemical probes to study the consequences of lipid metabolism modulation through non-redundant pathways.

MeSH terms

  • Acetyltransferases / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fatty Acid Desaturases / metabolism
  • Fatty Acid Elongases
  • Fatty Acids / metabolism*
  • Humans
  • Molecular Structure
  • Protein Kinases / metabolism*
  • Stearoyl-CoA Desaturase / antagonists & inhibitors*
  • Stearoyl-CoA Desaturase / metabolism
  • Structure-Activity Relationship
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry
  • Thiophenes / pharmacology*

Substances

  • Enzyme Inhibitors
  • Fatty Acids
  • Thiophenes
  • Fatty Acid Desaturases
  • SCD1 protein, human
  • Stearoyl-CoA Desaturase
  • Acetyltransferases
  • Fatty Acid Elongases
  • Protein Kinases