Salt of fused heterocyclic derivative and crystal thereof

Abstract

The present invention provides 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-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 for treating a sex hormone-dependent disease selected from the group consisting of benign prostatic hypertrophy, hysteromyoma, endometriosis, metrofibroma, precocious puberty, amenorrhea, premenstrual syndrome, dysmenorrhea, polycystic ovary syndrome, hirsutism, short stature, infertility, irritable bowel syndrome and prostate cancer, comprising administering an effective amount of a compound represented by the formula: ##STR00003##

2. The method of claim 1, wherein said sex-hormone dependent disease is endometriosis.

3. The method of claim 1, wherein said sex-hormone dependent disease is hysteromyoma.

4. The method of claim 1, wherein said sex-hormone dependent disease is prostate cancer.

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

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

7. The method of claim 1, wherein said compound has 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.

8. The method of claim 1, wherein said compound has 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 .sup.13C solid-state NMR spectrum.

9. The method of claim 1, wherein said compound has characteristic peaks at chemical shift values (δ (ppm)) of −131.6, −145.2, and −151.8 in a .sup.19F solid-state NMR spectrum.

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 (2θ(°)).

(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 (μv) 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 (δ(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 (2θ(°)).

(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 (δ(ppm)).