1, 4-benzoxazine compounds and derivatives thereof as therapeutic drugs for the treatment of neurodegenerative conditions
The present invention includes compositions and methods for inhibiting kinase activity to protect against neurodegeneration including diseases such as Alzheimer's disease, Parkinson's disease, or Huntington's disease, and conditions such as ischemic stroke comprising the step of providing the subject with a therapeutically affective amount of 1,4-benzoxazine compounds and derivatives thereof.
1. A pharmaceutical compound for reducing neuronal cell death in a subject comprising:
an effective amount of a composition of formula (I) disposed in a pharmaceutical carrier, wherein the effective amount is sufficient to reduce neuronal cell death in a subject:
wherein Ar is a phenyl substituted with one or more bromides, chlorides, hydroxyls or acetoxy groups;
X is O; R is a H; and G is an amine containing group.
2. The compound of claim 1 , wherein Ar is 3,5-dibromo-4-hydoxyphenyl.
3. The compound of claim 1 , wherein G is a NH 2 .
4. The compound of claim 1 , wherein Ar is 3, 5, dibromo-4-acetoxyphenyl and G is a NH 2 .
5. A method of reducing neuronal cell death in a subject in need thereof, comprising:
administering a composition comprising a compound according to claim 4 in an amount effective to reduce neurodegeneration.
6. The method according to claim 5 , wherein Ar is 3,5-dibromo-4-hydoxyphenyl.
7. The method according to claim 5 , wherein G is a NH 2 group.
8. The method according to claim 5 , wherein the neuronal cell death is associated with one or more of Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotropic lateral sclerosis, traumatic brain injury, a stroke, and an ischemic stroke.
9. A method of reducing activity of a kinase in a subject in need thereof, comprising:
administering a composition comprising a compound according to claim 1 in an amount effective to reduce activity of a kinase.
10. The method of claim 9 , further comprising measuring kinase activity level in the subject.
11. The method of claim 9 , wherein the kinase is selected from the group consisting of GSK3α, GSK3β, p38β, and B-Raf.
12. The method of claim 9 , wherein the kinase is selected from the group consisting of CDK1, CDK2, ROCK1, JNK2, MLK3, and c-Raf.
13. A composition having the structure
14. A method of reducing neuronal cell death in a subject in need thereof, comprising:
administering an amount effective of a composition to reduce neurodegeneration wherein the a composition having the structure
15. The method according to claim 14 , wherein the neuronal cell death is associated with one or more of Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotropic lateral sclerosis, traumatic brain injury, a stroke, and an ischemic stroke.
16. A method of reducing activity of a kinase in a subject in need thereof, comprising:
administering an amount effective of a composition to reduce activity of a kinase wherein the composition having the structure
17. The method of claim 16 , further comprising measuring kinase activity level in the subject.
18. The method of claim 16 , wherein the kinase is selected from the group consisting of GSK3α, GSK3β, p38β, and B-Raf.
19. The method of claim 16 , wherein the kinase is selected from the group consisting of CDK1, CDK2, ROCK1, JNK2, MLK3, and c-Raf.