Degradation of protein kinases by conjugation of protein kinase inhibitors with E3 ligase ligand and methods of use

US10925868B2 · kind B2 · utility

Assignee

• DANA-FARBER CANCER INSTITUTE, INC. · US

Inventors

• Nathanael S. Gray · Boston, US
• James E. Bradner · Weston, US
• Li Tan · Madison, US
• Hai-Tsang Huang · Boston, US
• Dennis Buckley · Boston, US
• Georg Winter · Brookline, US
• Mette Ishoey ROSENBAUM · Ringe, DK

Key dates

• Filing date: Nov 10, 2017
• Grant date: Feb 23, 2021
• Expiry date: Nov 10, 2037

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D487/04
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present application provides bifunctional compounds of Formula (I): or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for protein kinases (e.g., Bcr-Abl). The present application also relates to methods for the targeted degradation of one or more protein kinases through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to one or more protein kinases which can be utilized in the treatment of disorders modulated by protein kinases.