Synthesis of spiro[chroman-2,4'-piperidin]-4-one derivatives as acetyl-CoA carboxylase inhibitors

Bioorg Med Chem Lett. 2009 Feb 1;19(3):949-53. doi: 10.1016/j.bmcl.2008.11.099. Epub 2008 Dec 3.

Abstract

Various spiro[chroman-2,4'-piperidin]-4-one derivatives (38a-m and 43a-j) have been designed, synthesized and evaluated for in vitro acetyl-CoA carboxylase (ACC) inhibitory activity. Several compounds have shown ACC inhibitory activity in low nanomolar range. Compound 38j reduced the respiratory quotient (RQ) in C57BL/6J mice indicating increase in whole body fat oxidation even in the presence of high carbohydrate diet. Structure-activity relationship (SAR) has been discussed.

MeSH terms

  • Acetyl-CoA Carboxylase / antagonists & inhibitors*
  • Acetyl-CoA Carboxylase / chemistry
  • Adenosine Triphosphate / chemistry
  • Animals
  • Carbohydrates / chemistry
  • Chemistry, Pharmaceutical / methods*
  • Chromans / chemical synthesis*
  • Chromans / chemistry
  • Chromans / pharmacology
  • Drug Design
  • Inhibitory Concentration 50
  • Mice
  • Mice, Inbred C57BL
  • Models, Chemical
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship
  • Urea / chemistry

Substances

  • Carbohydrates
  • Chromans
  • Piperidines
  • Spiro Compounds
  • spiro(chroman-2,4'-piperidin)-4-one
  • Adenosine Triphosphate
  • Urea
  • Acetyl-CoA Carboxylase