Compositions for activating pyruvate kinase

• US 10,208,052 B1
• Filed: 03/20/2018
• Issued: 02/19/2019
• Est. Priority Date: 03/20/2017
• Status: Active Grant

• Current Assignee: Novo Nordisk Health Care AG (Novo Nordisk A/S)
• Original Assignee: Forma Therapeutics, Inc. (Novo Nordisk A/S)
• Inventors: Zheng, Xiaozhang, Green, Neal, Gustafson, Gary, Lancia, Jr., David R., Mitchell, Lorna, Shelekhin, Tatiana
• Primary Examiner(s): Davis, Brian J
• Application Number:
  US15/926,236
• Time in Patent Office: 336 Days
• Field of Search: None
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

Compositions for the activation of PKR are provided, as well as therapeutic administration of the compositions for the treatment of pyruvate kinase-related medical conditions, such as pyruvate kinase deficiency (PKD).

Claims

1. A composition comprising compound 1, or a pharmaceutically acceptable salt thereof:

2. The composition of claim 1, comprising the compound 1-(5-((3,4-Dihydro-2H-benzo[b][1,4]oxazin-6-yl)sulfonyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-2-hydroxy-2-methylpropan-1-one as a pharmaceutically acceptable salt.

3. The composition of claim 2, formulated as an oral unit dosage form.

4. A method of treating a patient diagnosed with a pyruvate kinase-related medical condition, the method comprising administering to the patient in need thereof a therapeutically effective amount of pharmaceutical composition comprising a compound 1-(5-((3,4-Dihydro-2H-benzo[b][1,4]oxazin-6-yl)sulfonyl)-3,4,5,6-tetrahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-2-hydroxy-2-methylpropan-1-one, or a pharmaceutically acceptable salt thereof.

5. The method of claim 4, wherein the method comprises oral administration of the pharmaceutical composition.

6. The method of claim 4, wherein the condition is pyruvate kinase deficiency (PKD).

7. A composition comprising compound 1 obtained by a process comprising the step of converting compound 4 into compound 1 in a reaction described as Step 4:

8. The composition of claim 7, wherein the process further comprises first obtaining the compound 4 from a compound 3 by a process comprising Step 3:

9. The composition of claim 8, wherein the process further comprises first obtaining the compound 3 from a compound 2 by a process comprising Step 2:

10. The composition of claim 9, wherein the process further comprises first obtaining the compound 2 from a process comprising Step 1: