Methods for treating a variety of diseases and conditions, and compounds useful therefor
In accordance with the present invention, there are provided novel compounds that have a variety of properties, i.e., antioxidant, anti-inflammatory, antiviral, antibacterial, and antifungal properties. Invention compounds, therefore, have the ability to impart a variety of beneficial physiological effects, e.g., to protect neurons and/or to promote neuroregeneration and/or to promote memory formation and/or to act as protein phosphatase or kinase inhibitors and/or to act as lipoxygenase inhibitors. Such compounds are useful for treatment of a variety of indications, including neurodegenerative diseases and conditions, diabetes, ischemia associated with heart disease, and memory deficit. In another aspect of the present invention, there are also provided formulations containing one or more of the above-described compounds, optionally further containing additional neurologically active compound(s) and/or adjuvants to facilitate delivery thereof across the blood/brain barrier. In still another aspect of the present invention, there are further provided methods for treating a wide variety of neurological indications, e.g., acute neural injuries, chronic injuries, promoting memory formation, and the like.
1. A compound having the structure of Formula (Ig):
or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof,
wherein:
R 2 is selected from the group consisting of H and methyl;
R 3 is trifluoromethyl or other fluoro substituted alkyl;
L 3 is a carbonyl; and
R 6 at each occurrence is independently selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, hydroxyl, alkoxy, substituted alkoxy, aryloxy, substituted aryloxy, mercapto, alkylthio, arylthio, carbonyl, aryl, substituted aryl, halogen, cyano, cyanoalkyl, nitro, amino, amidino, carbamate, S(O) n R 7 and C(O)R 8 ;
R 7 is H, R 9 , NH 2 , HNR 9 or NR 9 R 10 ;
R 8 is OH, OR 9 , NH 2 , NHR 9 or NR 9 R 10 ;
R 9 and R 10 at each occurrence are independently optionally substituted alkyl; and n=1 or 2.
2. The compound according to claim 1 having the structure of Formula (1):
3. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier therefor.
4. A method for treating acute neural injury, treating chronic neurodegenerative disease, protecting neurons in a subject in need thereof, or promoting neuroregeneration and/or memory formation in a subject in need thereof, said method comprising administering an effective amount of a compound according to claim 2 to said subject.
5. The method of claim 4 , wherein the chronic neurodegenerative disease is selected from the group consisting of: Alzheimer's disease, Parkinson's disease, Huntington's disease, amytrophical lateral sclerosis, and retinal degeneration.
6. The method of claim 4 , wherein the chronic neurodegenerative disease is Alzheimer's disease.
7. A composition comprising a compound according to claim 2 and a pharmaceutically acceptable carrier therefore.
8. The method of claim 4 , wherein the acute neural injury is stroke.
9. The compound according to claim 1 , wherein R 6 at each occurrence is selected from the group consisting of alkyl, substituted alkyl, hydroxyl, alkoxy, substituted alkoxy, halogen, and C(O)R 8 .
10. The compound according to claim 9 , wherein R 6 at each occurrence is selected from the group consisting of methyl, methoxy, perfluoromethyl, perfluoromethoxy, hydroxyl, Cl, F, and I.
11. A compound according to claim 1 having the structure of Formula II
or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof,
wherein:
(i) R A4 is H, R A3 is methoxy, R B2 is methyl, and R B4 is methyl; or
(ii) R A4 is methoxy, R A3 is H, R B2 is methyl, and R B4 is methyl; or
(iii)R A4 is H, R A3 is H, R B2 is H, and R B4 is H; or
(iv) R A4 is H, R A3 is H, R B2 is methyl, and R B4 is methyl; or
(v) R A4 is H, R A3 is methoxy, R B2 is H, and R B4 is H; or
(vi) R A4 is H, R A3 is H, R B2 is H, and R B4 is methyl; or
(vii) R A4 is H, R A3 is methoxy, R B2 is H, and R B4 is methyl; or
(viii) R A4 is H, R A3 is H, R B2 is methyl, and R B4 is H; or
(ix) R A4 is H, R A3 is methoxy, R B2 is methyl, and R B4 is H; or
(x) R A4 is COOH, R A3 is H, R B2 is methyl, and R B4 is methyl.
12. A composition comprising a compound according to claim 9 and a pharmaceutically acceptable carrier therefor.