US2005239840A1PendingUtilityA1

Benzothiophenes, formulations containing same, and methods

Individually held — no corporate assignee on recordPriority: Mar 26, 1996Filed: Mar 30, 2005Published: Oct 27, 2005
Est. expiryMar 26, 2016(expired)· nominal 20-yr term from priority
A61P 35/00A61P 19/10C07D 333/56
55
PatentIndex Score
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Claims

Abstract

This invention provides compounds of formula I and pharmaceutically acceptable salts and solvates thereof, characterized that the compound is in particulate form and having a specific size range. The present invention further provides pharmaceutical compositions containing or formulated using compounds of formula I, and the use of such compounds for alleviating human pathologies, including osteoporosis, serum lipid lowering, and breast cancer.

Claims

exact text as granted — not AI-modified
1 . A compound of formula I  
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts and solvates thereof, characterized in that the compound is in particulate form, said particles having a mean particle size of less than about 25 microns.  
   
   
       2 . The compound of  claim 1  wherein said particles have a mean particle size of between about 5 and about 20 microns.  
   
   
       3 . The compound of  claim 2  wherein at least about 90% of said particles have a size of less than about 50 microns.  
   
   
       4 . The compound of  claim 3  wherein at least 90% of said particles have a size of less than about 35 microns.  
   
   
       5 . A compound of  claim 1  which is the non-solvated crystalline 6-hydroxy-2-(4-hydroxy-phenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene hydrochloride having substantially the following X-ray diffraction pattern obtained with copper radiation:  
     
       
         
               
               
               
             
                   
                   
               
                   
                   
               
                   
                 d-line spacing 
                 I/I o   
               
                   
                 (Angstroms) 
                 (×100) 
               
                   
                   
               
                   
               
               
               
               
             
                   
                 13.3864 
                 71.31 
               
                   
                 9.3598 
                 33.16 
               
                   
                 8.4625 
                 2.08 
               
                   
                 7.3888 
                 7.57 
               
                   
                 6.9907 
                 5.80 
               
                   
                 6.6346 
                 51.04 
               
                   
                 6.1717 
                 29.57 
               
                   
                 5.9975 
                 5.67 
               
                   
                 5.9135 
                 9.87 
               
                   
                 5.6467 
                 38.47 
               
                   
                 5.4773 
                 10.54 
               
                   
                 5.2994 
                 4.74 
               
                   
                 4.8680 
                 4.03 
               
                   
                 4.7910 
                 5.98 
               
                   
                 4.6614 
                 57.50 
               
                   
                 4.5052 
                 5.75 
               
                   
                 4.3701 
                 9.03 
               
                   
                 4.2516 
                 69.99 
               
                   
                 4.2059 
                 57.64 
               
                   
                 4.1740 
                 65.07 
               
                   
                 4.0819 
                 12.44 
               
                   
                 3.9673 
                 22.53 
               
                   
                 3.9318 
                 100.00 
               
                   
                 3.8775 
                 9.07 
               
                   
                 3.7096 
                 33.38 
               
                   
                 3.6561 
                 21.65 
               
                   
                 3.5576 
                 3.36 
               
                   
                 3.5037 
                 7.97 
               
                   
                 3.4522 
                 18.02 
               
                   
                 3.4138 
                 4.65 
               
                   
                 3.2738 
                 10.23 
               
                   
                 3.1857 
                 8.90 
               
                   
                 3.1333 
                 6.24 
               
                   
                 3.0831 
                 9.43 
               
                   
                 3.0025 
                 12.13 
               
                   
                 2.9437 
                 4.96 
               
                   
                 2.8642 
                 7.70 
               
                   
                 2.7904 
                 11.95 
               
                   
                 2.7246 
                 3.05 
               
                   
                 2.6652 
                 3.32 
               
                   
                 2.5882 
                 7.30 
               
                   
                   
               
                   
                   
               
           
              
              
              
              
              
             
             
              
             
          
           
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
             
          
         
       
     
   
   
       6 . A pharmaceutical formulation comprising or formulated using the compound of  claim 5  and one or more pharmaceutically acceptable carriers, diluents, or excipients.  
   
   
       7 . A pharmaceutical composition comprising or formulated using a compound according to  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, in combination with one or more pharmaceutically acceptable carriers, diluents or excipients.  
   
   
       8 . A method of inhibiting osteoporosis comprising administering an effective amount of a compound of formula I to a person in need thereof.  
   
   
       9 . A method of lowering serum lipid levels comprising administering a compound of  claim 1 , or a pharmaceutically acceptable salt or solvate thereof, to a person in need thereof.  
   
   
       10 . A method for preventing breast cancer comprising administering to a woman in need thereof an effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt or solvate thereof.  
   
   
       11 . An article of manufacture comprising packaging material containing a pharmaceutical formulation, said packaging material further containing labelling indicating said pharmaceutical formulation is useful for inhibiting a human pathology, said pharmaceutical formulation comprising or formulated using a compound of  claim 1 .  
   
   
       12 . A compound of formula I  
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts and solvates thereof, characterized in that the compound is in particulate form, at least about 90% of said particles having a particle size of less than about 50 microns.  
   
   
       13 . The compound of  claim 12  wherein at least about 90% of said particles have a size of less than 35 microns.  
   
   
       14 . The compound of  claim 13  wherein said particles have a mean particle size of less than about 25 microns.  
   
   
       15 . The compound of  claim 14  wherein said particles have a mean particles size of between about 5 and about 20 microns.  
   
   
       16 . A compound of  claim 12  which is the non-solvated crystalline 6-hydroxy-2-(4-hydroxy-phenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene hydrochloride, having substantially the following X-ray diffraction pattern obtained with copper radiation:  
     
       
         
               
               
               
             
                   
                   
               
                   
                   
               
                   
                 d-line spacing 
                 I/I o   
               
                   
                 (Angstroms) 
                 (×100) 
               
                   
                   
               
                   
               
               
               
               
             
                   
                 13.3864 
                 71.31 
               
                   
                 9.3598 
                 33.16 
               
                   
                 8.4625 
                 2.08 
               
                   
                 7.3888 
                 7.57 
               
                   
                 6.9907 
                 5.80 
               
                   
                 6.6346 
                 51.04 
               
                   
                 6.1717 
                 29.57 
               
                   
                 5.9975 
                 5.67 
               
                   
                 5.9135 
                 9.87 
               
                   
                 5.6467 
                 38.47 
               
                   
                 5.4773 
                 10.54 
               
                   
                 5.2994 
                 4.74 
               
                   
                 4.8680 
                 4.03 
               
                   
                 4.7910 
                 5.98 
               
                   
                 4.6614 
                 57.50 
               
                   
                 4.5052 
                 5.75 
               
                   
                 4.3701 
                 9.03 
               
                   
                 4.2516 
                 69.99 
               
                   
                 4.2059 
                 57.64 
               
                   
                 4.1740 
                 65.07 
               
                   
                 4.0819 
                 12.44 
               
                   
                 3.9673 
                 22.53 
               
                   
                 3.9318 
                 100.00 
               
                   
                 3.8775 
                 9.07 
               
                   
                 3.7096 
                 33.38 
               
                   
                 3.6561 
                 21.65 
               
                   
                 3.5576 
                 3.36 
               
                   
                 3.5037 
                 7.97 
               
                   
                 3.4522 
                 18.02 
               
                   
                 3.4138 
                 4.65 
               
                   
                 3.2738 
                 10.23 
               
                   
                 3.1857 
                 8.90 
               
                   
                 3.1333 
                 6.24 
               
                   
                 3.0831 
                 9.43 
               
                   
                 3.0025 
                 12.13 
               
                   
                 2.9437 
                 4.96 
               
                   
                 2.8642 
                 7.70 
               
                   
                 2.7904 
                 11.95 
               
                   
                 2.7246 
                 3.05 
               
                   
                 2.6652 
                 3.32 
               
                   
                 2.5882 
                 7.30 
               
                   
                   
               
                   
                   
               
           
              
              
              
              
              
             
             
              
             
          
           
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
             
          
         
       
     
   
   
       17 . A pharmaceutical formulation comprising or formulated using the compound of  claim 16 , and one or more pharmaceutically acceptable carriers, diluents, or excipients.  
   
   
       18 . A pharmaceutical composition comprising or formulated using a compound according to  claim 12 , or a pharmaceutically acceptable salt or solvate thereof, with one or more pharmaceutically acceptable carriers, diluents or excipients.  
   
   
       19 . A method of inhibiting osteoporosis comprising administering to a person in need thereof an effective amount of a compound of  claim 12 , or a pharmaceutically acceptable salt or solvate thereof.  
   
   
       20 . A method of lowering serum lipid levels, comprising administering to a person in need thereof an effective amount of a compound of  claim 12 , or a pharmaceutically acceptable salt or solvate thereof.  
   
   
       21 . A method for preventing breast cancer comprising administering to a woman in need thereof an effective amount of a compound of  claim 12 , or a pharmaceutically acceptable salt or solvate thereof.  
   
   
       22 . An article of manufacture comprising packaging material containing a pharmaceutical formulation, said packaging material further containing labelling indicating said pharmaceutical formulation is useful for inhibiting a human pathology, said pharmaceutical formulation comprising or formulated using a compound of  claim 12 .  
   
   
       23 . A compound of formula I  
     
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts and solvates thereof, characterized in that the compound is in particulate form, said particles having a mean particle size of between about and about 20 microns, at least about 90% of said particles having a size of less than about 35 microns.  
   
   
       24 . A compound according to  claim 23  wherein it is the hydrochloride salt thereof.  
   
   
       25 . A compound of  claim 23  which is the non-solvated crystalline 6-hydroxy-2-(4-hydroxy-phenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b] thiophene hydrochloride, having substantially the following x-ray diffraction pattern obtained with copper radiation:  
     
       
         
               
               
               
             
                   
                   
               
                   
                   
               
                   
                 d-line spacing 
                 I/I o   
               
                   
                 (Angstroms) 
                 (×100) 
               
                   
                   
               
                   
               
               
               
               
             
                   
                 13.3864 
                 71.31 
               
                   
                 9.3598 
                 33.16 
               
                   
                 8.4625 
                 2.08 
               
                   
                 7.3888 
                 7.57 
               
                   
                 6.9907 
                 5.80 
               
                   
                 6.6346 
                 51.04 
               
                   
                 6.1717 
                 29.57 
               
                   
                 5.9975 
                 5.67 
               
                   
                 5.9135 
                 9.87 
               
                   
                 5.6467 
                 38.47 
               
                   
                 5.4773 
                 10.54 
               
                   
                 5.2994 
                 4.74 
               
                   
                 4.8680 
                 4.03 
               
                   
                 4.7910 
                 5.98 
               
                   
                 4.6614 
                 57.50 
               
                   
                 4.5052 
                 5.75 
               
                   
                 4.3701 
                 9.03 
               
                   
                 4.2516 
                 69.99 
               
                   
                 4.2059 
                 57.64 
               
                   
                 4.1740 
                 65.07 
               
                   
                 4.0819 
                 12.44 
               
                   
                 3.9673 
                 22.53 
               
                   
                 3.9318 
                 100.00 
               
                   
                 3.8775 
                 9.07 
               
                   
                 3.7096 
                 33.38 
               
                   
                 3.6561 
                 21.65 
               
                   
                 3.5576 
                 3.36 
               
                   
                 3.5037 
                 7.97 
               
                   
                 3.4522 
                 18.02 
               
                   
                 3.4138 
                 4.65 
               
                   
                 3.2738 
                 10.23 
               
                   
                 3.1857 
                 8.90 
               
                   
                 3.1333 
                 6.24 
               
                   
                 3.0831 
                 9.43 
               
                   
                 3.0025 
                 12.13 
               
                   
                 2.9437 
                 4.96 
               
                   
                 2.8642 
                 7.70 
               
                   
                 2.7904 
                 11.95 
               
                   
                 2.7246 
                 3.05 
               
                   
                 2.6652 
                 3.32 
               
                   
                 2.5882 
                 7.30 
               
                   
                   
               
                   
                   
               
           
              
              
              
              
              
             
             
              
             
          
           
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
             
          
         
       
     
   
   
       26 . A pharmaceutical formulation comprising or formulated using the compound of  claim 25  and one or more pharmaceutically-acceptable carriers, diluents, or excipients.  
   
   
       27 . A pharmaceutical composition comprising or formulated using a compound according to  claim 23 , or a pharmaceutically acceptable salt or solvate thereof, with one or more pharmaceutically acceptable carriers, diluents or excipients.  
   
   
       28 . A method for inhibiting osteoporosis comprising administering to a person in need thereof an effective amount of a compound of  claim 23 , or a pharmaceutically acceptable salt or solvate thereof.  
   
   
       29 . A method of lowering serum lipid levels, comprising administering an effective amount of a compound of  claim 23 , or a pharmaceutically acceptable salt or solvate thereof, to a person in need thereof.  
   
   
       30 . A method for preventing breast cancer comprising administering to a woman in need thereof an effective amount of a compound of  claim 23 , or a pharmaceutically acceptable salt or solvate thereof.  
   
   
       31 . An article of manufacture comprising packaging material containing a pharmaceutical formulation, said packaging material further containing labelling indicating said pharmaceutical formulation is useful for inhibiting a human pathology, said pharmaceutical formulation comprising or formulated using a compound of  claim 23.

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