Claims
- 1. A compound represented by Formula (I):
- 2. The compound of claim 1 wherein R3 is alkyl.
- 3. The compound of claim 2 wherein R3 is methyl.
- 4. The compound of claim 1 wherein R6 group is at the 3-position of the phenyl ring and is heteroalkyl, heterocyclylalkyl, —OR8 (wherein R8 is heteroalkyl or heterocyclylalkyl), —NHR10 (wherein R10 is heteroalkyl, heterosubstituted cycloalkyl, heterocyclyl, or heterocyclylalkyl), or —X-(alkylene) -Y-heteroalkyl (wherein X is a covalent bond, —O— or —NH— and Y is —O— or —NH).
- 5. The compound of claim 4 wherein R6 is (RS), (R) or (S) 2-hydroxy-2-hydroxymethyl-ethyloxy, 3-hydroxypropyloxy, 2-aminoethyloxy, 3-aminopropyloxy, 2-morpholin-4-ylethyloxy, or (RS), (-R) or (S) 2,2-dimethyl-1,3-dioxolan-4-ylmethyloxy.
- 6. The compound of claim 4 wherein R6 is (RS), (R) or (S) 2-hydroxy-2-hydroxymethylethylamino, 2-hydroxyethylamino, 3-hydroxypropylamino, (RS), (R) or (S) 2,2-dimethyl -1,3-dioxolan-4-ylmethylamino, 2-hydroxy-1-hydroxymethylethylamino, 3-hydroxybutylamino, or tetrahydropyran-4-ylamino.
- 7. The compound of claim 1 wherein R1 and R2 are hydrogen; R4 and R5 are at the 2 and the 6 positions of the phenyl ring and are independently of each other hydrogen or halogen; and R6 is at the 3-position of the phenyl ring.
- 8. The compound of claim 7 wherein R3 is alkyl or hydrogen, , R6 is —OR8 (wherein R8 is heteroalkyl or heterocyclylalkyl), —NHR10 (wherein R10 is heteroalkyl, heterosubstituted cycloalkyl, heterocyclyl, or heterocyclylalkyl), or —X-(alkylene)-Y-heteroalkyl (wherein X is a covalent bond, —O— or —NH— and Y is —O— or —NH).
- 9. The compound of claim 8 wherein R3 is methyl and R4 and R5 are independently of each other hydrogen, chloro, or fluoro.
- 10. The compound of claim 9 wherein R4 and R5 are hydrogen.
- 11. The compound of claim 10 wherein R6 is (RS), (R) or (S) 2-hydroxy-2-hydroxymethyl-ethyloxy, 3-hydroxypropyloxy, 2-aminoethyloxy, 3-aminopropyloxy, 2-morpholin-4-ylethyloxy, or (RS), (R) or (S) 2,2-dimethyl-1,3-dioxolan-4-ylmethyloxy.
- 12. The compound of claim 10 wherein R6 is (RS), (R) or (S) 2-hydroxy-2-hydroxymethylethylamino, 2-hydroxyethylamino, 3-hydroxypropylamino, (RS), (R) or (S) 2,2-dimethyl -1,3-dioxolan-4-ylmethylamino, 2-hydroxy-1-hydroxymethylethylamino, 3-hydroxybutylamino, or tetrahydropyran-4-ylamino.
- 13. The compound of claim 1 wherein R1 is at the 5-position of the indole ring and is halo; R2 is hydrogen; R4 and R5 are at the 2 and the 6 positions of the phenyl ring and are independently of each other hydrogen or halogen; and R6 is at the 3-position of the phenyl ring.
- 14. The compound of claim 13 wherein R3 is alkyl or hydrogen,, R6 is —OR8 (wherein R8 is heteroalkyl or heterocyclylalkyl), —NHR10 (wherein R10 is heteroalkyl, heterocyclyl, or heterocyclylalkyl), or -X-(alkylene)-Y-heteroalkyl (wherein X is a covalent bond, —O— or —NH— and Y is —O— or —NH).
- 15. The compound of claim 14 wherein R1 is chloro or fluoro; R3 is methyl; and R4 and R5 are independently of each other hydrogen, chloro, or fluoro.
- 16. The compound of claim 15 wherein R6 is (RS), (R) or (S) 2-hydroxy-2-hydroxymethyl-ethyloxy, 3-hydroxypropyloxy, 2-aminoethyloxy, 3-aminopropyloxy, 2-morpholin-4-ylethyloxy, or (RS), (R) or (S) 2,2-dimethyl-1,3-dioxolan-4-ylmethyloxy.
- 17. The compound of claim 14 wherein R6 is (RS), (R) or (S) 2-hydroxy-2-hydroxymethylethylamino, 2-hydroxyethylamino, 3-hydroxypropylamino, (RS), (R) or (S) 2,2-dimethyl -1,3-dioxolan-4-ylmethylamino, 2-hydroxy-1-hydroxymethylethylamino, 3-hydroxybutylamino, or tetrahydropyran-4-ylamino.
- 18. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable excipient.
- 19. A method of treating GSK-3β mediated diseases selected from Alzheimer's disease, obesity, diabetes, atherosclerotic cardiovascular disease, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency, cancer, allergy, and asthma in a mammal which method comprises administration to the mammal a therapeutically effective amount of a compound of claim 1.
- 20. The method of claim 19 wherein the disease is asthma.
- 21. A method of treating a patient having a disease characterized by an excess of CD4+ Th2 cytokines, comprising administering to the patient a therapeutically effective amount of an inhibitor of GSK-3β.
- 22. The method of claim 21, wherein the GSK-3β inhibitor is a compound of claim 1.
- 23. The method of claim 21, wherein the disease is asthma, allergy or allergic rhinitis.
- 24. The method of claim 21, wherein the disease is asthma.
- 25. The method of claim 21, wherein the GSK-3β inhibitor is at least 10 fold more selective for GSK-3β relative to PKC.
- 26. A method of treating a patient having a disease characterized by an excess IgE production, comprising administering to the patient a therapeutically effective amount of an inhibitor of GSK-3β.
- 27. The method of claim 26, wherein the GSK-3β inhibitor is a compound of claim 1.
- 28. The method of claim 26, wherein the disease is asthma.
- 29. The method of claim 26, wherein the GSK-3β inhibitor is at least 10 fold more selective for GSK-3β relative to PKC.
- 30. A method for preparing a compound of Formula (I) which comprises: reacting a 3-indol-3-yl-4-phenylfuran-2,5-dione of formula:
CROSS REFERENCE TO RELATED APPLICATION
[0001] Pursuant to 35 U.S.C. §119(e), this application claims priority to the filing date of the U.S. Provisional Patent Application Serial No. 60/221,058 filed on Jul. 27, 2000, the disclosure of which is herein incorporated by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60221058 |
Jul 2000 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
09916706 |
Jul 2001 |
US |
Child |
10139410 |
May 2002 |
US |