公开(公告)号：WO2020072830A1

公开(公告)日：2020-04-09

申请号：PCT/US2019/054583

申请日：2019-10-03

Applicant: THE JOHNS HOPKINS UNIVERSITY

Inventor： LIU, Jun ,  LI, Yingjun ,  PASUNOOTI, Kalyan, Kumar ,  LIU, Wukun ,  SHI, Wei ,  LI, Ruojing ,  HEAD, Sarah

IPC: A61K31/496 ,  A61K31/506 ,  C07D405/14

Abstract: Itraconazole, a widely used antifungal drug, has been found to possess potent anti-angiogenic and anti-hedgehog activities, exhibiting promising antitumor activity in several human clinical studies. The wider use of itraconazole in the treatment of cancer, however, has been limited by its potent inhibition of the drug metabolic enzyme CYP3A4 which causes drug-drug interactions. In an effort to eliminate the CYP3A4 inhibition of itraconazole while retaining its anti-angiogenic activity, we synthesized a series of itraconazole derivatives. The newly synthesized analogs of itraconazole were evaluated for their cytotoxicity against human umbilical vein endothelial cells (HUVEC) and their inhibitory activity against CYP3A4 enzyme.