Studies on hindered phenols and analogues. 1. Hypolipidemic and hypoglycemic agents with ability to inhibit lipid peroxidation

J Med Chem. 1989 Feb;32(2):421-8. doi: 10.1021/jm00122a022.


A series of hindered phenols were investigated as hypolipidemic and/or hypoglycemic agents with ability to inhibit lipid peroxidation. 1,3-Benzoxathioles (9 and 22), phenoxypentanoic acid (34), phenoxypentanol (35a), phenoxynonanol (35b), phenylchloropropionic acid having a chromanyl group (25), and a thiazolidine compound (27) derived from 25, all having a hindered phenol group, were prepared and examined. Compound 27 showed the expected biological properties in vivo and in vitro without any liver weight increase. Biological activities of the analogous thiazolidine compounds, 43-58, were compared. Thus, (+/-)-5-[4-[(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]- benzyl]-2,4-thiazolidinedione (27) (CS-045) was found to have all of our expected properties and was selected as a candidate for further development as a hypoglycemic and hypolipidemic agent.

MeSH terms

  • Animals
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / pharmacology*
  • Hypolipidemic Agents / chemical synthesis
  • Hypolipidemic Agents / pharmacology*
  • Lipid Peroxidation / drug effects*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Phenols / chemical synthesis
  • Phenols / pharmacology*
  • Rats
  • Structure-Activity Relationship


  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Phenols