Symmetrical approach of spiro-pyrazolidinediones as acetyl-CoA carboxylase inhibitors

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4769-72. doi: 10.1016/j.bmcl.2012.05.062. Epub 2012 May 19.


Spiro-pyrazolidinedione derivatives without quaternary chiral center were discovered by structure-based drug design and characterized as potent acetyl-CoA carboxylase (ACC) inhibitors. The high metabolic stability of the spiro-pyrazolo[1,2-a]pyridazine scaffold and enhancement of the activity by incorporation of a 7-methoxy group on the benzothiophene core successfully led to the identification of compound 4c as an orally bioavailable and highly potent ACC inhibitor. Oral administration of 4c significantly decreased the values of the respiratory quotient in rats, indicating the stimulation of fatty acid oxidation.

MeSH terms

  • Acetyl-CoA Carboxylase / antagonists & inhibitors*
  • Animals
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Microsomes / drug effects
  • Microsomes / enzymology
  • Models, Molecular
  • Molecular Structure
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology
  • Rats
  • Spiro Compounds / chemistry*
  • Spiro Compounds / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • Pyrazoles
  • Spiro Compounds
  • pyrazole
  • Acetyl-CoA Carboxylase