Highly potent and selective nonsteroidal dual inhibitors of CYP17/CYP11B2 for the treatment of prostate cancer to reduce risks of cardiovascular diseases

摘要

Dual CYP17/CYP11B2 inhibitors are proposed as a novel strategy for the treatment of prostate cancer to reduce risks of cardiovascular diseases. Via a combination of ligand- and structure-based approaches, a series of dual inhibitors were designed leading to the 2-(3-pyridyl)naphthalenes 10 and 11 with strong inhibition of both enzymes (IC_(50) values around 20 nM) and excellent selectivities over CYP11B1, CYP19, and CYP3A4. These compounds are considered as promising candidates for further in vivo evaluation.