Patent Evaluation: Thienopyridine Derivatives as Potent ACAT Inhibitors

Summary

Novelty: Thienopyridine derivatives which are said to show strong ACAT inhibitory activity are disclosed. These compounds may be useful for preventing or treating hypercholestrolaemia, atherosclerosis and ischaemic heart disease.

Biology: ACAT activity was calculated by measuring the amount of labelled cholesterol ester formed from [1-¹⁴C]oleoyl-CoA and endogenous cholesterol in male Sprague Dawley rats. The most effective compound had an ACAT inhibition rate of 82.3% at 0.5 μM.

Chemistry: Fifteen compounds are exemplified by synthesis. N-[4-(2-chlorophenyl)-2-ethylthieno[2,3-b]pyridin-5-yl]-N′-(2,4-diflurophenyl)urea is one of fifteen specifically claimed compounds.

Structure: