Patent Evaluation: Pyridine Derivatives as Androgen Biosynthesis Inhibitors

Summary

Novelty: 3-Substituted pyridines are disclosed which are stated to be active as selective inhibitors of androgen biosynthesis, inhibiting the steroid 17α-hydroxylase/C_17-20lyase enzyme complex essential for androgen synthesis but having lesser activity against aromatase activity essential for oestrogen synthesis. Such selective androgen biosynthesis inhibitors are potentially useful for the treatment of androgen-dependent tumours, such as prostatic cancer.

Biology: In vitro studies of the inhibition of enzyme activity showed that selected compounds inhibited human lyase with IC₅₀ values between 0.016-0.600 μM, but inhibited human placental aromatase with greater IC₅₀ values between 21.0-35.0 μM.

Chemistry: Synthesis of the compounds was by conventional methods, fully described and exemplified in twelve cases, including (1S,2S,3S,5R)-isopinocampheyl-2-(3-pyridyl)propanoate.