Ethanol Solvate of (-)-cis-2-(2-chlorophenyl)-5,7-dihydroxy-8-[4R-(3S-hydroxy-1-methyl)piperidinyl]-4H-1-benzopyran-4-one

Abstract

An ethanol solvate form of (−)-cis-2-(2-chlorophenyl)-5,7-dihydroxy-8-[4R-(3S-hydroxy-1-methyl)piperidinyl]-4H-1-benzopyran-4-one hydrochloride (Form II), a method of making Form II and a composition comprising Form II.

1 . A method for treating a cancer in a patient comprising administering to said patient a therapeutically effective amount of anhydrous Form II of (−)-cis-2-(2-chlorophenyl)-5,7-dihydroxy-8-[4R-(3S-hydroxy-1-methyl)piperidinyl]-4H-1-benzopyran-4-one hydrochloride ethanol solvate having an X-ray powder diffraction pattern,  
       
         
           
                 
               
                     
                 
                     
                 
                   D Space- Å 
                 
                     
                 
                     
                 
                 
               
                   12.763 
                 
                   6.389 
                 
                   3.194 
                 
                   13.244 
                 
                   4.259 
                 
                     
                 
                     
                 
             
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
               
            
           
         
       
       expressed in terms of D-spacing wherein the cancer is selected from the group consisting of leukemia, mesothelioma, lung cancer, colorectal cancer, breast cancer, ovarian cancer, prostate cancer, melanoma, cancer of the uterine body and cancer of the central nervous system.  
     
     
         2 . A method for treating a cancer in a patient comprising administering to said patient a therapeutically effective amount of anhydrous Form II of (−)-cis-2-(2-chlorophenyl)-5,7-dihydroxy-8-[4R-(3S-hydroxy-1-methyl)piperidinyl]-4H-1-benzopyran-4-one hydrochloride ethanol solvate having an X-ray powder diffraction pattern,  
       
         
           
                 
                 
               
                     
                 
                     
                 
                   D Space- Å 
                   Relative Intensity 
                 
                     
                 
                     
                 
                 
                 
               
                   12.763 
                   Strong 
                 
                   6.389 
                   Medium 
                 
                   3.194 
                   Weak 
                 
                   13.244 
                   Weak 
                 
                   4.259 
                   Weak 
                 
                   12.036 
                   Weak 
                 
                   2.824 
                   Weak 
                 
                   8.659 
                   Weak 
                 
                   6.012 
                   Weak 
                 
                   5.397 
                   Weak 
                 
                   3.447 
                   Weak 
                 
                     
                 
                     
                 
             
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       expressed in terms of D-spacing and relative intensity wherein the cancer is selected from the group consisting of leukemia, mesothelioma, lung cancer, colorectal cancer, breast cancer, ovarian cancer, prostate cancer, melanoma, cancer of the uterine body and cancer of the central nervous system.  
     
     
         3 . A method for treating a cancer in a patient comprising administering to said patient a therapeutically effective amount of anhydrous Form I of (−)-cis-2-(2-chlorophenyl)-5,7-dihydroxy-8-[4R-(3S-hydroxy-1-methyl)piperidinyl]-4H-1-benzopyran-4-one hydrochloride ethanol solvate having an X-ray powder diffraction pattern,  
       
         
           
                 
                 
                 
                 
               
                     
                 
                     
                 
                     
                     
                   Relative 
                   Relative Intensity 
                 
                   2 Theta Angle (°) 
                   D Space- Å 
                   Intensity 
                   (%) 
                 
                     
                 
                     
                 
                 
                 
                 
                 
               
                   6.920 
                   12.763 
                   Strong 
                   100.0 
                 
                   13.850 
                   6.389 
                   Medium 
                   35.7 
                 
                   27.908 
                   3.194 
                   Weak 
                   22.2 
                 
                   6.669 
                   13.244 
                   Weak 
                   18.0 
                 
                   20.838 
                   4.259 
                   Weak 
                   13.8 
                 
                   7.339 
                   12.036 
                   Weak 
                   13.8 
                 
                   31.660 
                   2.824 
                   Weak 
                   9.5 
                 
                   10.208 
                   8.659 
                   Weak 
                   8.3 
                 
                   14.722 
                   6.012 
                   Weak 
                   7.2 
                 
                   16.413 
                   5.397 
                   Weak 
                   6.9 
                 
                   25.829 
                   3.447 
                   Weak 
                   6.5 
                 
                     
                 
                     
                 
             
                
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       expressed in terms of 2 theta angle, D-spacing, relative intensity and % relative intensity wherein the cancer is selected from the group consisting of leukemia, mesothelioma, lung cancer, colorectal cancer, breast cancer, ovarian cancer, prostate cancer, melanoma, cancer of the uterine body and cancer of the central nervous system.