β- and γ-diketones and γ-hydroxyketones as WNT/β-catenin signaling pathway activators

Patent metadata

Field	Value
Publication number	US-9884053-B2
Application number	US-201615349118-A
Country	US
Kind code	B2
Filing date	Nov 11, 2016
Priority date	Aug 18, 2010
Publication date	Feb 6, 2018
Grant date	Feb 6, 2018

Abstract

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.

First claim

What is claimed is:

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 , w

Assignees

• Samumed Llc

Inventors

• Kc Sunil Kumar
• Wallace David Mark
• Hood John
• Barroga Charlene F

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title