Stabilization of hypoxia inducible factor (HIF) alpha

• US 20110166145A1
• Filed: 12/02/2010
• Published: 07/07/2011
• Est. Priority Date: 12/06/2001
• Status: Active Grant

• Current Assignee: FibroGen, Inc
• Original Assignee: FibroGen, Inc
• Inventors: Melekhov, Alex, Guenzler-Pukall, Volkmar, Neff, Thomas B., Wang, Qingjian, Flippin, Lee A., Arend, Michael P.
• Granted Patent: US 8,466,172 B2
• Time in Patent Office: Days
• US Class Current: 514/248
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• 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 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4418 having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/472 Non-condensed isoquinolines, e.g. papaverine
• CPC Class Codes: A61K 31/4738 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/63 Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
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• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
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• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
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• 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 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
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• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• 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: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07K 14/4702 : Regulators; Modulating activity
• CPC Class Codes: C07K 14/505 : Erythropoietin [EPO]
• CPC Class Codes: G01N 33/746 : Erythropoetin

Abstract

The present invention relates to methods of stabilizing the alpha subunit of hypoxia inducible factor (HIF). The invention further relates to methods of preventing, pretreating, or treating conditions associated with HIF, including ischemic and hypoxic conditions. Compounds for use in these methods are also provided.

Claims

1. A method for treating tissue damage associated with hypoxia or ischemia in a subject, the method comprising administering to the subject an effective amount of a compound that stabilizes the alpha subunit of hypoxia inducible factor (HIFα

).

2. The method of claim 1, wherein the compound is a heterocyclic carboxamide compound that inhibits HIF prolyl hydroxlase enzyme activity.

3. The method of claim 1, wherein the tissue damage is associated with an ischemic event.

4. The method of claim 3, wherein the ischemic event is acute.

5. The method of claim 3, wherein the ischemic event is associated with surgery, organ transplantation, infarction, trauma, or injury.

6. The method of claim 1, wherein the ischemia is chronic.

7. The method of claim 1, wherein the tissue damage is associated with ischemic reperfusion injury in a subject.

8. The method of claim 1, wherein the administering is oral administration.

9. A method for stabilizing the alpha subunit of hypoxia inducible factor (HIFα

) in a subject, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound that inhibits HIF prolyl hydroxylase enzyme activity.