Inhibitors of phosphoglycerate dehydrogenase (PHGDH) and uses thereof

US11225469B2 · kind B2 · utility

Assignees

• Whitehead Institute For Biomedical Research · US
• DANA-FARBER CANCER INSTITUTE, INC. · US
• The United States of America, as represented by the Secretary, Department of Health and Human Services · US

Inventors

• David M. Sabatini · Cambridge, US
• Michael Pacold · Boston, US
• Matthew B. Boxer · Point of Rocks, US
• Jason Rohde · Poolesville, US
• Kyle Ryan Brimacombe · Bethesda, US
• Min-Jui Richard Shen · Boyds, US
• Ganesha Rai Bantukallu · Falls Church, US
• Li Liu · Doylestown, US

Key dates

• Filing date: Jan 15, 2016
• Grant date: Jan 18, 2022
• Expiry date: Jan 15, 2036

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D249/14
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention provides compounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.