Patent Evaluation: Azadecalin Amides as Cholesterol Biosynthesis Inhibitors

Summary

Novelty: Azadecalin amides and thioamides are disclosed. These compounds are said to inhibit cholesterol biosynthesis by virtue of their squalene epoxidase and/or oxidosqualene cyclase inhibitory activity and are potentially useful for the prevention of arteriosclerosis.

Biology: Oxidosqualene cyclase inhibition was demonstrated in vitro in HepG2 cells and against purified liver microsomal enzyme; two selected compounds showed IC₅₀ values of 0.7 and 52.0 μM.

Chemistry: Synthesis of the compounds is outlined in a multistep preparative scheme which is exemplified in seventeen cases. The compound N-[1-oxo-5-(3-methyl-butylmercapto)pentyl]-8-aza-4α,10-dimethyl-trans-decalin-3β-ol is specifically claimed.

Structure: