Enhanced Erythropoiesis and Iron Metabolism

• US 20140142136A1
• Filed: 11/19/2013
• Published: 05/22/2014
• 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., Stephenson, Robert C., Guenzler-Pukall, Volkmar
• Granted Patent: US 9,920,011 B2
• Time in Patent Office: Days
• US Class Current: 514/309
• 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 erythropoiesis and iron metabolism, and for treating or preventing iron deficiency and anemia of chronic disease.

Claims

1-60. -60. (canceled)

61. A method for overcoming or ameliorating cytokine-induced impairment of erythropoiesis in a subject in need thereof, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound that stabilizes HIFα

, thereby overcoming or ameliorating the cytokine-induced impairment of erythropoiesis in the subject.

62. The method of claim 61, wherein the cytokine-induced impairment of erythropoiesis is suppression of EPO production.

63. The method of claim 61, wherein the cytokine-induced impairment of erythropoiesis is impairment of iron metabolism.

64. The method of claim 61, wherein the cytokine is an inflammatory cytokine.

65. The method of claim 61, wherein the cytokine is selected from the group consisting of TNF-α

, IL-1β

, and IFN-γ

.

66. A method for overcoming or ameliorating cytokine-induced increase in VCAM-1 expression in a subject in need thereof, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound that stabilizes HIFα

, thereby overcoming or ameliorating the cytokine-induced increase in VCAM-1 expression in the subject.

67. A method for overcoming or ameliorating cytokine-induced increase in E-selectin expression in a subject in need thereof, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound that stabilizes HIFα

, thereby overcoming or ameliorating the cytokine-induced increase in E-selectin expression in the subject.

68. A method for treating or preventing a disorder associated with cytokine activity in a subject in need thereof, wherein the disorder is selected from the group consisting of iron deficiency, functional iron deficiency, iron deficiency anemia, anemia of chronic disease, and microcytic anemia, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound that stabilizes HIFα

, thereby treating or preventing the disorder associated with cytokine activity.

69. A method for treating or preventing a disorder associated with cytokine activity in a subject in need thereof, wherein the disorder is associated with a condition selected from the group consisting of an inflammation, an infection, an immunodeficiency disorder, and a neoplastic disorder, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound that stabilizes HIFα

, thereby treating or preventing the disorder associated with cytokine activity.

70. A method for increasing erythropoietin (EPO) production in the presence of an inflammatory cytokine in a subject in need thereof, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound that stabilizes HIFα

, thereby increasing EPO production in the subject.

78. The method of claim 70, wherein the inflammatory cytokine is selected from the group consisting of TNF-α

, IL-1β

, and IFN-γ

.

71-77. -77. (canceled)