[摘要]：17a-hydroxylase-17,20-lyase inhibitor (CYP17), is currently undergoing phase II clin. trials as a potential drug for the treatment of androgen-dependent prostate cancer. Since steroidal compds. often show side effects attributable to their structure, we have tried to replace the sterane scaffold by nonsteroidal core structures. The design and synthesis of 20 new abiraterone mimetics are described. Their activities have been tested with recombinant human CYP17 expressed in E. coli. Promising compds. were further evaluated for selectivity against CYP11B1, CYP11B2, and the hepatic CYP3A4. Compds. I and II showed comparable activity to abiraterone (IC50 values of 144 and 64 nM vs 72 nM) and similar or even better selectivity against the other CYP enzymes. Selected compds. were also docked into our homol. model, and the same binding modes as for abiraterone were found.
