Methods for inhibiting bone loss

Abstract

The current invention provides methods and pharmaceutical formulations that are useful for inhibiting the loss of bone. These methods and formulations can be used without the associated adverse effects of estrogen therapy, and thus serve as an effective and acceptable treatment for osteoporosis.

1. A method of inhibiting post- menopausal  bone loss in a postmenopausal woman in need of treatment to prevent or to treat post- menopausal osteoporosis  comprising administering to a human said woman in need of said treatment an amount of a compound of Formula I 
                 
 
       wherein
 X is a bond, CH 2 , or CH 2 CH 2 ;  
 R and R 1 , independently, are hydrogen, hydroxyl, C 1 -C 6 -alkoxy, C 1 -C 6 -acyloxy, C 1 -C 6 -akoxy-C 2 -C 6 -acyloxy, R 3 -substituted aryloxy, R 3 -substituted aroyloxy, R 4 -substituted carbonyloxy, chloro, or bromo;  
 R 2  is a heterocyclic ring selected from the group consisting of pyrrolidino, piperidino, and hexamethyleneimino;  
 R 3  is C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, hydrogen, or halo; and  
 R 4  is C 1 -C 6 -alkoxy or aryloxy; or a pharmaceutically acceptable salt thereof, that is effective to inhibit post- menopausal  bone loss in a human said woman.  
 
     
     
       2. A method of  claim 1  wherein the human woman has been diagnosed as suffering from post- menopausal  osteoporosis. 
     
     
       3. A method of  claim 1  wherein the human is a post-menopausal female. 
     
     
       4. A method of  claim 1  wherein the human is a male. 
     
     
       5. A method of  claim 1  wherein the compound is administered prophylactically. 
     
     
       6. A method of  claim 1  wherein X is a bond. 
     
     
       7. A method of  claim 1  wherein R 2  is piperidino or pyrrolidino. 
     
     
       8. A method of  claim 6  wherein R 2  is piperidino or pyrrolidino. 
     
     
       9. A method of  claim 6  wherein R 2  is piperidino. 
     
     
       10. A method of  claim 6  wherein R 2  is pyrrolidino. 
     
     
       11. A method of  claim 1  wherein R and R 1  are both hydroxyl, C 1 -C 6 -acyloxy, C 1 -C 6 -alkoxy-C 2 -C 6 -acyloxy, R 3 -substituted aroyloxy, or R 4 -substituted carbonyloxy. 
     
     
       12. A method of  claim 11  wherein R and R 1  are both hydroxyl. 
     
     
       13. A method of  claim 11  wherein R and R 1  are both C 1 -C 6 -acyloxy. 
     
     
       14. A method of  claim 13  wherein R and R 1  are both n-butanoyloxy, 2,2-dimethylpropanoyloxy, or 3,3-dimethylbutanoyloxy. 
     
     
       15. A method of  claim 11  wherein R and R 1  are both R 4 -substituted carbonyloxy. 
     
     
       16. A method of  claim 15  wherein R and R 1  are both methoxycarbonyloxy or phenyloxycarbonyloxy. 
     
     
       17. A method of  claim 11  wherein R and R 1  are both R 3 -substituted aroyloxy. 
     
     
       18. A method of  claim 17  wherein R and R 1  are both benzoyloxy, methylbenzoyloxy, or naphthoyloxy. 
     
     
       19. A method of  claim 8  wherein R and R 1  are both hydroxyl, C 1 -C 6 -acyloxy, C 1 -C 6 -alkoxy-C 2 -C 6 -acyloxy, R 3 -substituted aroyloxy, or R 4 -substituted carbonyloxy. 
     
     
       20. A method of  claim 9  wherein R and R 1  are both hydroxyl. 
     
     
       21. A method of  claim 10  wherein R and R 1  are both hyroxyl. 
     
     
       22. A method of  claim 8  wherein R and R 1  are both C 1 -C 6 -acyloxy. 
     
     
       23. A method of  claim 22  wherein R and R 1  are both n-butanoyloxy, 2,2-dimethylpropanoyloxy, or 3,3-dimethylbutanoyloxy. 
     
     
       24. A method of  claim 8  wherein R and R 1  are both R 4 -substituted carbonyloxy. 
     
     
       25. A method of  claim 24  wherein R and R 1  are both methoxycarbonyloxy or phenyloxycarbonyloxy. 
     
     
       26. A method of  claim 8  wherein R and R 1  are both R 3 -substituted aroyloxy. 
     
     
       27. A method of  claim 26  wherein R and R 1  are both benzoyloxy, methylbenzoyloxy, or naphthoyloxy. 
     
     
       28. A method of  claim 1  wherein the compound of formula I is administered in an amount of 0.1 to 1000 mg. 
     
     
       29. A method of  claim 1  wherein the compound of formula I is administered in an amount of 200 to 600 mg. 
     
     
       30. A method of  claim 1  wherein the compound of formula I is administered in an amount of 600 to 1000 mg. 
     
     
       31. A method of  claim 20  wherein the human woman has been diagnosed as suffering from post- menopausal  osteoporosis. 
     
     
       32. A method of  claim 20  wherein the human is a post-menopausal woman. 
     
     
       33. A method of  claim 20  wherein the compound is administered prophylactically. 
     
     
       34. A method of  claim 1  wherein the administration of a compound of formula I does not significantly affect the primary six target tissues. 
     
     
       35. A method of  claim 1  wherein a compound of formula I is administered in combination with estrogen.