Salt of fused heterocyclic derivative and crystal thereof

Abstract

The present invention provides 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyl-oxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid choline salt having excellent solubility and storage stability.

1 . A method for preventing or treating a sex hormone-dependent disease in a subject, said method comprising administering to said subject a therapeutically effective amount of a compound represented by the formula: 
       
         
           
           
               
               
           
         
       
     
     
         2 . The method of  claim 1 , wherein said sex-hormone dependent disease is selected from the group consisting of benign prostatic hypertrophy, hysteromyoma, endometriosis, metrofibroma, precocious puberty, amenorrhea, premenstrual syndrome, dysmenorrhea, polycystic ovary syndrome, lupus erythematosis, hirsutism, short stature, sleep disorders, acne, baldness, Alzheimer's disease, infertility, and irritable bowel syndrome. 
     
     
         3 . The method of  claim 1 , wherein said sex-hormone dependent disease is a cancer. 
     
     
         4 . The method of  claim 3 , wherein said cancer is selected from the group consisting of prostate cancer, ovary cancer, uterine cancer, and breast cancer. 
     
     
         5 . The method of  claim 1 , wherein said compound is administered orally. 
     
     
         6 . The method of  claim 1 , wherein said subject is a human. 
     
     
         7 . The method of  claim 1 , wherein said compound is crystalline. 
     
     
         8 . The method of  claim 7 , wherein said compound exhibits characteristic peaks at diffraction angles (2θ(°)) of 7.1, 11.5, 19.4, 20.3, 21.5, 22.0, 22.6, 23.5, and 26.2 in a powder X-ray diffraction diagram. 
     
     
         9 . The method of  claim 7 , wherein said compound is characterized by an X-ray powder diffraction spectrum substantially as depicted in  FIG. 1 . 
     
     
         10 . The method of  claim 7 , wherein said compound exhibits characteristic peaks at chemical shift values (δ(ppm)) of 155.8, 149.8, 145.3, 118.0, 113.7, 111.6, 110.3, 98.1, 69.8, 58.7, 57.1, and 55.5 in a  13 C solid-state nuclear magnetic resonance (NMR) spectrum. 
     
     
         11 . The method of  claim 7 , wherein said compound is characterized by a  13 C solid-state NMR spectrum substantially as depicted in  FIG. 3 . 
     
     
         12 . The method of  claim 7 , wherein said compound exhibits characteristic peaks at chemical shift values (δ(ppm)) of −131.6, −145.2, and −151.8 in a  19 F solid-state NMR spectrum. 
     
     
         13 . The method of  claim 7 , wherein said compound is characterized by a  19 F solid-state NMR spectrum substantially as depicted in  FIG. 5 . 
     
     
         14 . The method of  claim 7 , wherein said compound exhibits an endotherm at about 213° C. as measured by differential thermal analysis. 
     
     
         15 . The method of  claim 7 , wherein said compound is characterized by a differential thermal analysis curve substantially as depicted in  FIG. 2 . 
     
     
         16 . The method of  claim 7 , wherein said compound is characterized by a thermogravimetric analysis curve substantially as depicted in  FIG. 2 . 
     
     
         17 . The method of  claim 1 , said method comprising administering to said subject a pharmaceutical composition comprising said therapeutically effective amount of said compound. 
     
     
         18 . The method of  claim 17 , wherein said pharmaceutical composition is a tablet or capsule.