Methods for increasing the stabilization of hypoxia inducible factor-1 alpha
AssigneeAerpio Therapeutics Inc.
InventorsRobert Shalwitz, Joseph H. Gardner
Life of this patent
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Abstract
Disclosed herein are methods for controlling the activity of hypoxia-inducible transcription factor 1-alpha (HIF-1α) and diseases, conditions, or syndromes related thereto, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, and anemia. Further disclosed are pharmaceutical compositions comprising HIF-1α prolyl hydroxylase inhibitors useful in treating diseases, conditions, and/or syndromes related thereto the activity of HIF-1α.
Claims20
A method for inhibiting hypoxia-inducible factor-1alpha (HIF-1α) 4-prolyl hydroxylase activity in a subject, comprising administering to a subject a HIF-1α prolyl hydroxylase inhibitor having the formula:
- wherein L is chosen from CH2 or SO2;
- Z has the formula:
- R represents from 0 to 5 substitutions for hydrogen;
- the index n is an integer from 0 to 5;
- R1 and R2 are each independently chosen from:
- i) hydrogen;
- ii) substituted or unsubstituted C1-C10 linear, C3-C10 branched, or C3-C10 cyclic alkyl;
- iii) substituted or unsubstituted C2-C10 linear, C3-C10 branched, or C3-C10 cyclic alkenyl;
- iv) substituted or unsubstituted C2-C10 linear or C3-C10 branched alkynyl;
- v) substituted or unsubstituted C6 or C10 aryl;
- vi) substituted or unsubstituted C1-C9 heterocyclic;
- vii) substituted or unsubstituted C1-C9 heteroaryl;
- or
- viii) R1 and R2 can be taken together to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring having from form 2 to 20 carbon atoms and from 1 to 7 heteroatoms;
- or
- a pharmaceutically acceptable salt thereof.
A method for increasing the cellular immune response of a subject having an inflammatory disease, comprising administering to a subject an effective amount of a HIF-1α prolyl hydroxylase inhibitor having the formula:
- wherein Z is phenyl substituted with from 1 to 5 halogens chosen from fluorine and chlorine;
- R4 is C1-C4 linear alkyl or C3-C4 branched alkyl;
- or a pharmaceutically acceptable salt thereof.
A method of controlling the immune response in a subject having an inflammatory disease, comprising administering to the subject a HIF-1α prolyl hydroxylase inhibitor having the formula:
- wherein Z is phenyl substituted with from 1 to 5 halogens chosen from fluorine and chlorine;
- R4 is C1-C4 linear alkyl or C3-C4 branched alkyl;
- or
- a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.