Itraconazole analogs and use thereof

US12071430B2 · kind B2 · utility

Assignee

• THE JOHNS HOPKINS UNIVERSITY · US

Inventors

• Jun O. Liu · Clarksville, US
• Yingjun Li · Baltimore, US
• Kalyan Kumar Pasunooti · Baltimore, US
• Wukun Liu · Baltimore, US
• Wei Shi · 安丰镇, CN
• Ruojing Li · Baltimore, US
• Sarah Head · Baltimore, US

Key dates

• Filing date: Oct 3, 2019
• Grant date: Aug 27, 2024
• Expiry date: Jan 5, 2041

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K31/506
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

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.