Prolylhydroxylase/ATF4 inhibitors and methods of use for treating neural cell injury or death and conditions resulting therefrom
Methods for treating a patient suffering from neural cell injury, the method comprising administering to the patient an effective amount of a HIF prolyl-4-hydroxylase inhibiting compound having the following general formula (1) wherein R 1 is a cyclic group containing at least three and up to seven carbon atoms and optionally containing one or more heteroatoms selected from O, N, and S, and optionally attached to the shown carbon atom by a linking group; R 2 is independently selected from said cyclic groups of R 1 and acyclic hydrocarbon groups R 5 containing up to twenty carbon atoms; R 3 is selected from hydrogen atom and hydrocarbon groups containing up to six carbon atoms; R 6 and R 7 are independently selected from hydrogen atom, hydrocarbon groups containing up to three carbon atoms, halogen atom, and polar groups, as well as methylene-linked versions thereof; and t is 0 or 1.
1. A method for treating a patient suffering from mild traumatic brain injury, the method comprising administering to said patient an effective amount of a HIF prolyl-4-hydroxylase inhibiting compound having the following general formula:
wherein:
R 1 is a phenyl ring optionally substituted with a halogen atom or methyl group; and
R 2 is a pyridine ring optionally substituted with an —OR 4 group, wherein R 4 is hydrogen atom or methyl.
2. The method of claim 1 , wherein said HIF prolyl-4-hydroxylase inhibiting compound inhibits ATF-4.
3. The method of claim 1 , wherein said mild traumatic brain injury is associated with intracerebral hemorrhage.
4. The method of claim 1 , wherein said HIF prolyl-4-hydroxylase inhibiting compound decreases edema.
5. The method of claim 1 , wherein said patient exhibits somatosensory, sensorimotor, or motor improvement after treatment with said HIF prolyl-4-hydroxylase inhibiting compound.
6. The method of claim 1 , wherein said HIF prolyl-4-hydroxylase inhibiting compound has the following structure:
7. The method of claim 1 , wherein said mild traumatic brain injury is neurotoxic-induced.
8. The method of claim 1 , wherein R 1 is a phenyl ring optionally substituted with a halogen atom.
9. The method of claim 1 , wherein R 2 is a pyridine ring optionally substituted with an OH group.