title: Highly potent and selective nonsteroidal dual inhibitors of CYP17/CYP11B2 for the treatment of prostate cancer to reduce risks of cardiovascular diseases.
abstract: 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 (IC50 values around 20 nM) and excellent selectivities over CYP11B1, CYP19, and CYP3A4. These compounds are considered as promising candidates for further in vivo evaluation.
authors.affiliation: Pharmaceutical and Medicinal Chemistry, Saarland University & Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Campus C2-3, D-66123 Saarbrücken, Germany.
authors.forename: Mariano A E
authors.initials: MA
authors.lastname: Pinto-Bazurco Mendieta
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Hu
authors.forename: Matthias
authors.initials: M
authors.lastname: Engel
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002460:Cell Line; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors*; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D009281:Naphthalenes; D011725:Pyridines; D051544:Cytochrome P-450 CYP3A; D013254:Steroid 17-alpha-Hydroxylase; C510163:CYP3A4 protein, human; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase