β- and γ-diketones and γ-hydroxyketones as
The present application discloses a compound which is which activates Wnt/β-catenin signaling and thus treats or prevents diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries related to the differentiation and development of the central nervous system, comprising Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, comprising hair loss, hematopoiesis related diseases and tissue regeneration related diseases.
1. A method for promoting healing of bone fractures, bone defects, craniofacial defects, otosclerosis or osteogenesis imperfecta in a subject, the method comprising administering to the subject a compound of Formula I, or a pharmaceutically acceptable salt thereof:
wherein R 1 is a substituted or unsubstituted heteroaryl, wherein the heteroaryl is selected from the group consisting of
with the proviso that a carbon atom of the R 1 heteroaryl is attached to the carbonyl;
R 2 is selected from the group consisting of a substituted or unsubstituted
and a substituted or unsubstituted aryl, wherein the aryl is selected from phenyl or naphthyl; and
R 3 , R 4 , R 5 and R 6 are H.
2. The method of claim 1 , wherein R 1 is a substituted or unsubstituted
3. The method of claim 1 , wherein R 1 is a substituted or unsubstituted
4. The method of claim 1 , wherein R 1 is a substituted or unsubstituted
5. The method of claim 1 , wherein R 2 is a substituted or unsubstituted
6. The method of claim 2 , wherein R 2 is a substituted or unsubstituted phenyl.
7. The method of claim 1 having a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
8. The method of claim 7 , wherein the compound of Formula I is:
or a pharmaceutically acceptable salt thereof.
9. The method of claim 7 , wherein the compound of Formula I is:
or a pharmaceutically acceptable salt thereof.
10. The method of claim 7 , wherein the compound of Formula I is:
or a pharmaceutically acceptable salt thereof.
11. A method of treating osteoporosis in a subject, the method comprising administering to the subject a compound of Formula I, or a pharmaceutically acceptable salt thereof:
wherein R 1 is a substituted or unsubstituted heteroaryl, wherein the heteroaryl is selected from the group consisting of
with the proviso that a carbon atom of the R 1 heteroaryl is attached to the carbonyl;
R 2 is selected from the group consisting of a substituted or unsubstituted
and a substituted or unsubstituted aryl, wherein the aryl is selected from phenyl or naphthyl; and
R 3 , R 4 , R 5 and R 6 are H.
12. The method of claim 11 , wherein R 1 is a substituted or unsubstituted
13. The method of claim 11 , wherein R 1 is a substituted or unsubstituted
14. The method of claim 11 , wherein R 1 is a substituted or unsubstituted
15. The method of claim 12 , wherein R 2 is a substituted or unsubstituted
16. The method of claim 12 , wherein R 2 is a substituted or unsubstituted phenyl.
17. The method of claim 11 having a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
18. The method of claim 17 , wherein the compound of Formula I is:
or a pharmaceutically acceptable salt thereof.
19. The method of claim 17 , wherein the compound of Formula I is:
or a pharmaceutically acceptable salt thereof.
20. The method of claim 17 , wherein the compound of Formula I is:
or a pharmaceutically acceptable salt thereof.
21. The method of claim 11 , wherein the osteoporosis is glucocorticoid-induced osteoporosis.
22. The method of claim 11 , wherein the osteoporosis is hyperthyroidism-induced osteoporosis.
23. The method of claim 11 , wherein the osteoporosis is immobilization-induced osteoporosis.
24. The method of claim 11 , wherein the osteoporosis is heparin-induced osteoporosis.
25. The method of claim 11 , wherein the osteoporosis is immunosuppressive-induced osteoporosis.
26. A method for treating a bone condition in a subject, wherein the bone condition is selected from the group consisting of childhood idiopathic bone loss, alveolar bone loss, mandibular bone loss, osteotomy, and bone loss associated with periodontitis, the method comprising administering to the subject a compound of Formula I, or a pharmaceutically acceptable salt thereof:
wherein R 1 is a substituted or unsubstituted heteroaryl, wherein the heteroaryl is selected from the group consisting of
with the proviso that a carbon atom of the R 1 heteroaryl is attached to the carbonyl;
R 2 is selected from the group consisting of a substituted or unsubstituted
and a substituted or unsubstituted aryl, wherein the aryl is selected from phenyl or naphthyl; and
R 3 , R 4 , R 5 and R 6 are H.
27. The method of claim 26 , wherein R 1 is a substituted or unsubstituted
28. The method of claim 26 , wherein R 1 is a substituted or unsubstituted
29. The method of claim 26 , wherein R 1 is a substituted or unsubstituted
30. The method of claim 27 , wherein R 2 is a substituted or unsubstituted
31. The method of claim 27 , wherein R 2 is a substituted or unsubstituted phenyl.
32. The method of claim 26 having a structure selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
33. The method of claim 32 , wherein the compound of Formula I is:
or a pharmaceutically acceptable salt thereof.
34. The method of claim 32 , wherein the compound of Formula I is:
or a pharmaceutically acceptable salt thereof.
35. The method of claim 32 , wherein the compound of Formula I is:
or a pharmaceutically acceptable salt thereof.
36. The method of claim 1 , wherein the subject is a human.
37. The method of claim 11 , wherein the subject is a human.
38. The method of claim 26 , wherein the subject is a human.
39. The method of claim 26 , wherein the bone condition is treated by reducing loss of bone mass or bone density.
40. The method of claim 26 , wherein the bone condition is treated by increasing bone mass or bone density.
41. The method of claim 26 , wherein the bone condition is treated by maintaining bone mass or bone density.
42. The method of claim 26 , wherein the bone condition is treated by reducing loss of calcium from bone.