Ketone carbonyl-containing hydrophobic antitumor drug and conjugate thereof as well as nano preparation containing conjugate, preparation method therefor, and application thereof

US11833128B2 · kind B2 · utility

Assignee

• Jiangsu Jibeier Pharmaceutical Co. Ltd. · CN

Inventors

• Deyue Yan · Shanghai, CN
• Zhongyi Geng · Zhenjiang, CN
• Yao Wang · Shanghai, CN
• Xinyuan Zhu · Shanghai, CN
• Wei Huang · Stony Brook, US
• Yongfeng Zhou · Dongguan, CN

Key dates

• Filing date: Mar 5, 2019
• Grant date: Dec 5, 2023
• Expiry date: Apr 4, 2040

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D407/12
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present disclosure provides a ketone carbonyl-containing hydrophobic antitumor drug and a conjugate thereof as well as a nano preparation containing the conjugate, a preparation method therefor, and an application thereof. The conjugate is an amphipathic pH-responsive conjugate obtained by enabling a dehydration condensation reaction between a hydrazide-terminated polyethylene glycol and/or lactose hydrazide and the ketone carbonyl-introduced hydrophobic antitumor drug. The ketone carbonyl-introduced hydrophobic antitumor drug is obtained by reacting an isocyanate group in a compound containing isocyanate group and ketone carbonyl group with a hydroxyl on a hydroxyl-containing hydrophobic antitumor drug. The hydroxyl-containing hydrophobic antitumor drug includes at least one of paclitaxel, docetaxel, paclitaxel derivatives, or docetaxel derivatives. Compared with docetaxel, the ketone carbonyl-containing hydrophobic antitumor drug, the conjugate thereof and the nano preparation have higher antitumor activity.