Enhanced erythropoiesis and iron metabolism

• US 10,894,774 B2
• Filed: 04/27/2017
• Issued: 01/19/2021
• Est. Priority Date: 06/06/2003
• Status: Active Grant

• Current Assignee: FibroGen, Inc
• Original Assignee: FibroGen, Inc
• Inventors: Klaus, Stephen J., Molineaux, Christopher J, Neff, Thomas B, Guenzler-Pukall, Volkmar, Stephenson, Robert C., Seeley, Todd W., Langsetmo Parobok, Ingrid
• Primary Examiner(s): Lundgren, Jeffrey S
• Assistant Examiner(s): Schmitt, Michael J
• Application Number:
  US15/498,856
• Publication Number:
  US 20170224673A1
• Time in Patent Office: 1,363 Days
• Field of Search: None
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/395 having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• CPC Class Codes: A61K 31/472 Non-condensed isoquinolines, e.g. papaverine
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07C 275/40 being further substituted by nitrogen atoms not being part of nitro or nitroso groups
• CPC Class Codes: C07D 217/24 Oxygen atoms

Abstract

The present invention relates to methods and compounds for regulating or enhancing erthropoiesis and iron metabolism, and for treating or preventing iron deficiency and anemia of chronic disease.

Claims

1. A method for decreasing hepcidin in a subject in need thereof, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound that stabilizes the alpha subunit of hypoxia-inducible factor (HIFα

), thereby decreasing hepcidin in the subject, wherein the heterocyclic carboxamide compound is a compound of Formula 1;

2. The method of claim 1, wherein the subject is a subject having anemia.

3. The method of claim 2, wherein the anemia is anemia of chronic disease.

4. The method of claim 1, wherein the subject is a subject having a chronic disease selected from the group consisting of an inflammation, an infection, an immunodeficiency disorder, and a neoplastic disorder.

5. The method of claim 1, wherein the subject is a subject having iron deficiency.

6. The method of claim 5, when the iron deficiency is functional iron deficiency.

7. The method of claim 1, wherein the heterocyclic carboxamide compound inhibits hypoxia-inducible factor prolyl hydroxylase enzyme activity.

8. The method of claim 1, wherein the subject is a human.

9. The method of claim 8, wherein the compound is orally administered to the human.

10. A method for decreasing hepcidin expression in a subject in need thereof, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound that stabilizes the alpha subunit of hypoxia-inducible factor (HIFα

), thereby decreasing hepcidin expression in the subject, wherein the heterocyclic carboxamide compound is a compound of Formula I;

11. The method of claim 10, wherein the subject is a subject having anemia.

12. The method of claim 10, wherein the subject is a subject having iron deficiency.

13. The method of claim 12, when the iron deficiency is functional iron deficiency.

14. The method of claim 10, wherein the heterocyclic carboxamide compound inhibits hypoxia-inducible factor prolyl hydroxylase enzyme activity.

15. The method of claim 10, wherein the subject is a human.

16. The method of claim 15, wherein the compound is orally administered to the human.

17. A method for decreasing hepcidin expression in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula I:

18. The method of claim 17, wherein the subject is a subject having anemia.

19. The method of claim 17, wherein the subject is a subject having iron deficiency.

20. The method of claim 19, when the iron deficiency is functional iron deficiency.

21. The method of claim 17, wherein the heterocyclic carboxamide compound inhibits hypoxia-inducible factor prolyl hydroxylase enzyme activity.

22. The method of claim 17, wherein the subject is a human.

23. The method of claim 22, wherein the compound is orally administered to the human.