Compositions and methods for inhibiting dihydroorotate dehydrogenase

US11230528B2 · kind B2 · utility

Assignee

• Clear Creek Bio, Inc.

Inventors

• Vikram Kumar
• David P. Hesson · Malvern, US
• Ping Huang · Mountain View, US
• Mo Jia · Shanghai, CN
• Xianjun You · Shanghai, CN

Key dates

• Filing date: Dec 4, 2020
• Grant date: Jan 25, 2022
• Expiry date: Dec 4, 2040

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D215/52
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The invention provides therapeutic compositions that contain an inhibitor of dihydroorotate dehydrogenase (DHODH) and promote sustained elevation of dihydroorotate (DHO) levels in a patient. The compositions are useful for treating disorders associated with unregulated DHODH activity, such as acute myeloid leukemia. The invention also provides methods of determining therapeutically effective doses of compositions that contain a DHODH inhibitor. The invention further provides methods of synthesis of 2-(2′-halo-1-1′-biphenyl-4-yl)-quinoline carboxylic acids, which are useful as DHODH inhibitors.