26,27-homologated-20-EPI-2-alkylidene-19-nor-vitamin D compounds

Abstract

This invention provides a novel class of vitamin D related compounds, namely, the 2-alkylidene-19-nor-vitamin D derivatives, as well as a general method for their chemical synthesis. The compounds have the formula: where Y 1 and Y 2 , which may be the same or different, are each selected from the group consisting of hydrogen and a hydroxy-protecting group, R 6 and R 8 , which may be the same or different, are each selected from hydrogen, alkyl, hydroxyalkyl and fluoroalkyl, or when taken together represent the group —(CH 2 ) X — where X is an integer from 2 to 5, and where the group R represents any of the typical side chains known for vitamin D type compounds. These 2-substituted compounds are characterized by relatively high intestinal calcium transport activity and relatively high bone calcium mobilization activity resulting in novel therapeutic agents for the treatment of diseases where bone formation is desired, particularly low bone turnover osteoporosis. These compounds also exhibit pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as anti-cancer agents and for the treatment of diseases such as psoriasis.

1 - 48 . (canceled) 
   
   
       49 . A method of treating acne comprising administering to a patient with acne an effective amount of 20(S)-1α,25-dihydroxy-2-methylene-26,27-dihomo-19-norvitamin D 3  having the structure 
     
       
         
         
             
             
         
       
     
   
   
       50 . The method of  claim 49  wherein the compound is administered orally. 
   
   
       51 . The method of  claim 49  wherein the compound is administered parenterally. 
   
   
       52 . The method of  claim 49  wherein the compound is administered transdermally. 
   
   
       53 . The method of  claim 49  wherein the compound is administered topically. 
   
   
       54 . The method of  claim 49  wherein said effective amount comprises about 0.01 μg/day to about 100 μg/day of 20(S)-1α,25-dihydroxy-2-methylene-26,27-dihomo-19-norvitamin D 3 . 
   
   
       55 . The method of  claim 49  wherein said effective amount comprises about 0.1 μg/day to about 50 μg/day of 20(S)-1α,25-dihydroxy-2-methylene-26,27-dihomo-19-norvitamin D 3 . 
   
   
       56 . A method of treating acne comprising administering to a patient with acne an effective amount of 20(S)-26,27-dimethylene-25-methoxy-2-methylene-19-norvitamin D 3  having the structure 
     
       
         
         
             
             
         
       
     
   
   
       57 . The method of  claim 56  wherein the compound is administered orally. 
   
   
       58 . The method of  claim 56  wherein the compound is administered parenterally. 
   
   
       59 . The method of  claim 56  wherein the compound is administered transdermally. 
   
   
       60 . The method of  claim 56  wherein the compound is administered topically. 
   
   
       61 . The method of  claim 56  wherein said effective amount comprises about 0.01 μg/day to about 100 μg/day of 20(S)-26,27-dimethylene-25-methoxy-2-methylene-19-norvitamin D 3 . 
   
   
       62 . The method of  claim 56  wherein said effective amount comprises about 0.1 μg/day to about 50 μg/day of 20(S)-26,27-dimethylene-25-methoxy-2-methylene-19-norvitamin D 3 . 
   
   
       63 . A method of treating acne comprising administering to a patient with acne an effective amount of 20(S)-1α,25-dihydroxy-26,27-dimethylene-2-methylene-19-norvitamin D 3  having the structure 
     
       
         
         
             
             
         
       
     
   
   
       64 . The method of  claim 63  wherein the compound is administered orally. 
   
   
       65 . The method of  claim 63  wherein the compound is administered parenterally. 
   
   
       66 . The method of  claim 63  wherein the compound is administered transdermally. 
   
   
       67 . The method of  claim 63  wherein the compound is administered topically. 
   
   
       68 . The method of  claim 63  wherein said effective amount comprises about 0.01 μg/day to about 100 μg/day of 20(S)-1α,25-dihydroxy-26,27-dimethylene-2-methylene-19-norvitamin D 3 . 
   
   
       69 . The method of  claim 63  wherein said effective amount comprises about 0.1 μg/day to about 50 μg/day of 20(S)-1α,25-dihydroxy-26,27-dimethylene-2-methylene-19-norvitamin D 3 . 
   
   
       70 . A method of treating acne comprising administering to a patient with acne an effective amount of 20(S)-26,27-dimethylene-1α-hydroxy-2-methylene-24-dehydro-19-norvitamin D 3  having the structure 
     
       
         
         
             
             
         
       
     
   
   
       71 . The method of  claim 70  wherein the compound is administered orally. 
   
   
       72 . The method of  claim 70  wherein the compound is administered parenterally. 
   
   
       73 . The method of  claim 70  wherein the compound is administered transdermally. 
   
   
       74 . The method of  claim 70  wherein the compound is administered topically. 
   
   
       75 . The method of  claim 70  wherein said effective amount comprises about 0.01 μg/day to about 100 μg/day of 20(S)-26,27-dimethylene-1α-hydroxy-2-methylene-24-dehydro-19-norvitamin D 3 . 
   
   
       76 . The method of  claim 70  wherein said effective amount comprises about 0.1 μg/day to about 50 μg/day of 20(S)-26,27-dimethyl-1α-hydroxy-2-methylene-24-dehydro-19-norvitamin D 3 .