Patent Evaluation: Novel Non-Steroidal Aromatase Inhibitors

Summary

Novelty: Fluoromethylphenyl derivatives bearing a heterocyclic group are disclosed as aromatase inhibitors. These compounds are potentially useful in the treatment of oestrogen-dependent illnesses such as gynaecomastia and breast cancer.

Biology: No specific data are provided, however the compounds are said to inhibit aromatase activity in vitro in placental microsomes. IC₅₀ values below 10^–9 M are reported for the conversion of [¹⁴C]-androstenedione to [¹⁴C]-oestrogen. The compounds are also said to inhibit aromatase in vivo in rats with MED values between 0.001–1.0 mg/kg sc, and to promote regression of DMBA-induced mammary tumours in rats at doses of 1.0 mg/kg po.

Chemistry: Synthesis of the compounds is outlined in a series of multistep preparative schemes, forming a subsidiary part of the claim and exemplified in eighteen cases. The compound 4-[α-(4-cyanophenyl)-α-fluoro-1-(1,2,3-triazolyl) methyl]benzonitrile is the only specifically claimed compound.

Structure: