Patent Evaluation: The use of Tocotrienol for Cholesterol and Lipid Lowering

Summary

Novelty: Structurally novel, acyclic tocotrienol analogues, which may be useful for cholesterol/lipid lowering in cases of hypercholesterolaemia, hyperlipidaemia and atherosclerosis, are disclosed.

Biology: The in vitro cholesterol biosynthesis inhibition activity and the in vitro HMG-CoA reductase suppresion activity of the compounds in HepG2 cells were found to be 99% and 53% at 10μM, respectively. An in vivo biological evaluation of the compounds in normocholesterolaemic chickens was also carried out, the specific activity of HMGR, total serum cholesterol levels. LDL cholesterol and HDL cholesterol pools were also determined.

Chemistry: The syntheses of the compounds are outlined in three schemes and described in thirty seven examples. 3,5-Dimethyl-4-[(5,9,13-trimethyl-4(E),8(E),12-tetradecatrienyl)oxy]-phenol is one of thirty specifically claimed examples.

Structure: