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US-12617766-B2 - Crystal form of thiophene derivative and preparation method therefor

US12617766B2US 12617766 B2US12617766 B2US 12617766B2US-12617766-B2

Abstract

Provided are a crystal form of a compound represented by formula (I) and a preparation method therefor.

Inventors

  • Yang Zhang
  • Wentao Wu
  • Zhixiang Li
  • Wenyuan ZHU

Assignees

  • TONGHUA DONGBAO PHARMACEUTICAL CO., LTD.

Dates

Publication Date
20260505
Application Date
20220421
Priority Date
20210429

Claims (20)

  1. 1 . A crystal form C of a compound of formula (I), wherein the crystal form C has an X-ray powder diffraction pattern comprising characteristic diffraction peaks at the following 2θ angles: 13.20±0.20°, 15.26±0.20°, 18.08±0.20°, 21.99±0.20°, 25.07=0.20°, 25.38±0.20°, 26.66±0.20°, and 30.70=0.20°,
  2. 2 . The crystal form C according to claim 1 , wherein the X-ray powder diffraction pattern thereof has characteristic diffraction peaks at the following 2θ angles: 9.03±0.20°, 13.20=0.20°, 15.26=0.20°, 18.08±0.20°, 21.99-0.20°, 25.07=0.20°, 25.38=0.20°, 26.66=0.20°, 28.38±0.20°, 29.41±0.20°, 30.70±0.20°, and 38.53-0.20°.
  3. 3 . The crystal form C according to claim 1 , wherein the X-ray powder diffraction pattern thereof has characteristic diffraction peaks at the following 2θ angles: 13.20°, 15.26°, 18.08°, 21.99°, 25.07°, 25.38°, 26.66°, and 30.70°.
  4. 4 . The crystal form C according to claim 1 , wherein the X-ray powder diffraction pattern thereof has characteristic diffraction peaks at the following 2θ angles: 5.66°, 9.03°, 11.13°, 13.20°, 13.70°, 15.26°, 17.25°, 18.08°, 18.92°, 20.88°, 21.99°, 23.41°, 24.09°, 25.07°, 25.38°, 25.99°, 26.66°, 27.17°, 28.38°, 29.41°, 29.98°, 30.70°, 31.02°, 31.72°, 33.67°, 35.40°, 36.35°, 36.74°, 37.26°, 38.53°, and 39.80°.
  5. 5 . The crystal form C according to claim 1 , wherein the crystal form C has an XRPD pattern basically as shown in FIG. 5 .
  6. 6 . The crystal form C according to claim 1 , wherein the crystal form C has a thermogravimetric analysis curve with a weight loss of 1.21% at 200° C.±3° C.
  7. 7 . The crystal form C according to claim 6 , wherein the crystal form C has a TGA pattern as shown in FIG. 6 .
  8. 8 . The crystal form C according to claim 1 , wherein the crystal form C has a differential scanning calorimetry curve comprising an endothermic peak with an onset at 250.0° C.±2° C.
  9. 9 . The crystal form C according to claim 8 , wherein the crystal form C has a DSC pattern as shown in FIG. 7 .
  10. 10 . A crystal form E of a compound of formula (I), wherein the crystal form E has an X-ray powder diffraction pattern comprising characteristic diffraction peaks at the following 2θ angles: 9.11±0.20°, 12.43=0.20°, 13.28=0.20°, 15.34±0.20°, 18.16±0.20°, 22.06=0.20°, 23.15±0.20°, and 25.14±0.20°,
  11. 11 . The crystal form E according to claim 10 , wherein the X-ray powder diffraction pattern thereof has characteristic diffraction peaks at the following 2θ angles: 9.11=0.20°, 11.21±0.20°, 12.43±0.20°, 13.28±0.20°, 15.34±0.20°, 18.16=0.20°, 22.06±0.20°, 23.15±0.20°, 25.14±0.20°, 25.97±0.20°, 26.75±0.20°, and 27.25±0.20°.
  12. 12 . The crystal form E according to claim 10 , wherein the X-ray powder diffraction pattern thereof has characteristic diffraction peaks at the following 2θ angles: 9.11°, 12.43°, 13.28°, 15.34°, 18.16°, 22.06°, 23.15°, and 25.14°.
  13. 13 . The crystal form E according to claim 10 , wherein the X-ray powder diffraction pattern thereof has characteristic diffraction peaks at the following 2θ angles: 9.11°, 10.94°, 11.21°, 12.43°, 13.28°, 15.34°, 17.39°, 18.16°, 18.94°, 20.18°, 20.95°, 22.06°, 23.15°, 23.35°, 24.19°, 25.14°, 25.97°, 26.75°, 27.25°, 28.45°, 29.49°, 30.16°, 30.82°, 33.74°, 35.45°, 36.39°, 37.34°, and 38.57°.
  14. 14 . The crystal form E according to claim 10 , wherein the crystal form E has an XRPD pattern basically as shown in FIG. 11 .
  15. 15 . The crystal form E according to claim 10 , wherein the crystal form E has a thermogravimetric analysis curve with a weight loss of 0.79% at 200° C.±3° C.
  16. 16 . The crystal form E according to claim 15 , wherein the crystal form E has a TGA pattern as shown in FIG. 12 .
  17. 17 . The crystal form E according to claim 10 , wherein the crystal form E has a differential scanning calorimetry curve comprising an endothermic peak with an onset at 250.4° C.±2° C.
  18. 18 . The crystal form E according to claim 17 , wherein the crystal form E has a DSC pattern as shown in FIG. 13 .
  19. 19 . A method for treating gout and hyperuricemia in a subject in need thereof, comprising administering the crystal form C according to claim 1 to the subject.
  20. 20 . A method for treating gout and hyperuricemia in a subject in need thereof, comprising administering the crystal form E according to claim 10 to the subject.

Description

The present application is a National Stage of International Application No. PCT/CN2022/088295, filed on Apr. 21, 2022, which claims priorities of the Chinese Patent Application No. CN202110472705.3 filed on Apr. 29, 2021, the Chinese Patent Application No. CN202111112439.X filed on Sep. 18, 2021. TECHNICAL FIELD The present disclosure relates to a crystal form of a thiophene derivative and a preparation method thereof, specifically to a crystal form of formula (I) and a preparation method thereof. BACKGROUND Gouty arthritis is a common and complex type of arthritis. When the concentration of uric acid in the human blood exceeds 7 mg/dL, uric acid is deposited in the joints, cartilage, and kidneys in the form of monosodium salt, leading to an overactive (sensitive) immune system, thus causing painful inflammation. The common areas attacked are the metatarsophalangeal joint, ankle joint, knee joint, etc. Hyperuricemia is the pathological basis of gouty arthritis. Hyperuricemia refers to a disorder in the metabolism of purine substances within the human body, resulting in an increase in uric acid synthesis or a decrease in its excretion, leading to an abnormally high level of uric acid in the blood. Internationally, the standards for diagnosis of hyperuricemia (HUA) are defined as: under normal purine dietary conditions, fasting blood uric acid levels measured twice on different days exceed 400 μmol/L (6.8 mg/dL) for men and 360 μmol/L (6 mg/dL) for women. It can be categorized into three types, underexcretion of uric acid, overproduction of uric acid, or mixed type. Clinical research indicates that 90% of primary hyperuricemia falls under the category of underexcretion of uric acid. Hyperuricemia is inextricably linked with gout and is an independent risk factor for metabolic diseases [such as diabetes, metabolic syndrome (MS), hyperlipidemia], chronic kidney disease, cardiovascular disease, and stroke. Therefore, reducing the level of uric acid in the human body can be conducive not only to the treatment or prevention of hyperuricemia and gout but also to lowering the risk of other complications associated with hyperuricemia. There are two sources of purines within the human body: endogenous purines, originating from self-synthesis or nucleic acid breakdown (approximately 600 mg/d), and exogenous purines, derived from dietary intake of purines (approximately 100 mg/d). Under normal conditions, the uric acid pool in the body amounts to 1200 mg, with about 700 mg of uric acid produced daily. Of this, ⅔ is excreted through the kidneys, ⅓ through the intestines, and a very small amount is excreted through the sweat glands. Therefore, the commonly used uric acid-lowering drugs in clinical practice include xanthine oxidase (XO) inhibitors (such as allopurinol and febuxostat) that suppress uric acid production, and Urat1 inhibitors that promote uric acid excretion (such as benzbromarone and lesinurad). Xanthine oxidase is an enzyme with low specificity; it can catalyze the conversion from hypoxanthine into xanthine and subsequently into uric acid, as well as directly catalyze the conversion from xanthine to uric acid. Xanthine oxidase inhibitors are first-line options for treating hyperuricemia, with allopurinol and febuxostat being the primary marketed medications. However, such drugs do not meet the clinical needs of all patients and have noticeable side effects. Allopurinol is the only uric acid-lowering therapeutic agent available worldwide, but it can lead to serious adverse skin events. Severe hypersensitivity reactions related to allopurinol are closely associated with the human leukocyte antigen (HLA)-B*5801, with the Chinese population having a higher incidence of HLA-B*5801 positivity (6% to 8%) compared to Caucasians (about 2%), thus increasing the risk of hypersensitivity reactions. Febuxostat has a superior uric acid-lowering effect compared to allopurinol, but even at high doses of 80 mg per day, 40% to 52% of patients do not achieve the expected uric acid reduction target, and it may increase the incidence of acute gout attacks. There is still an unmet clinical need in the market for safe and effective uric acid-lowering drugs. Content of the Present Invention The present disclosure provides a crystal form A of a compound of formula (I), wherein the crystal form A has an X-ray powder diffraction pattern comprising characteristic diffraction peaks at the following 2θ angles: 12.35±0.20°, 15.05±0.20°, 18.19±0.20°, 20.10±0.20°, 23.05±0.20°, 25.05±0.20°, 25.87±0.20°, and 27.16±0.20°, In some embodiments of the present disclosure, the X-ray powder diffraction pattern of the crystal form A has characteristic diffraction peaks at the following 2θ angles: 10.89±0.20°, 12.35±0.20°, 13.42±0.20°, 15.05±0.20°, 18.19±0.20°, 20.10±0.20°, 21.82±0.20°, 23.05±0.20°, 25.05±0.20°, 25.87±0.20°, 27.16±0.20°, and 30.28±0.20°. In some embodiments of the present disclosure, the X-ray powder diffraction pattern of the cryst