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.

Claims

1. A method of treating dysmenorrhea in a subject, said method comprising administering to said subject a therapeutically effective amount of a compound represented by the formula: ##STR00003##

2. The method of claim 1, wherein said compound is administered orally.

3. The method of claim 1, wherein said subject is a human.

4. The method of claim 1, wherein said compound is crystalline.

5. The method of claim 4, wherein said compound exhibits characteristic peaks at diffraction angles (2()) 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.

6. The method of claim 4, wherein said compound is characterized by an X-ray powder diffraction spectrum substantially as depicted in FIG. 1.

7. The method of claim 4, wherein said compound exhibits characteristic peaks at chemical shift values ((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 .sup.13C solid-state nuclear magnetic resonance (NMR) spectrum.

8. The method of claim 4, wherein said compound is characterized by a .sup.13C solid-state NMR spectrum substantially as depicted in FIG. 3.

9. The method of claim 4, wherein said compound exhibits characteristic peaks at chemical shift values ((ppm)) of 131.6, 145.2, and 151.8 in a .sup.19F solid-state NMR spectrum.

10. The method of claim 4, wherein said compound is characterized by a .sup.19F solid-state NMR spectrum substantially as depicted in FIG. 5.

11. The method of claim 4, wherein said compound exhibits an endotherm at about 213 C. as measured by differential thermal analysis.

12. The method of claim 4, wherein said compound is characterized by a differential thermal analysis curve substantially as depicted in FIG. 2.

13. The method of claim 4, wherein said compound is characterized by a thermogravimetric analysis curve substantially as depicted in FIG. 2.

14. The method of claim 1, said method comprising administering to said subject a pharmaceutical composition comprising said therapeutically effective amount of said compound.

15. The method of claim 14, wherein said pharmaceutical composition is a tablet or capsule.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a powder X-ray diffraction diagram of compound (A) obtained in Example 1. The vertical axis shows X-ray diffraction intensity (Counts); and the horizontal axis shows diffraction angle(2()).

(2) FIG. 2 is a diagram representing the TG-DTA measurement of compound (A) obtained in Example 1. The vertical axis (left) shows weight (%) in a thermogravimetric (TG) curve; the vertical axis (right) shows heat flux (v) in a differential thermal analysis (DTA) curve; and the horizontal axis shows temperature ( C.).

(3) FIG. 3 is a .sup.13C solid-state NMR spectrum chart of compound (A) obtained in Example 1. The vertical axis shows intensity; and the horizontal axis shows chemical shift value ((ppm)).

(4) FIG. 4 is a powder X-ray diffraction diagram of compound (B) obtained in Comparative Example 1. The vertical axis shows X-ray diffraction intensity (Counts); and the horizontal axis shows diffraction angle (2()).

(5) FIG. 5 is a .sup.19F solid-state NMR spectrum chart of compound (A) obtained in Example 1. The vertical axis shows intensity; and the horizontal axis shows chemical shift value ((ppm)).