Salts and solid forms of a compound that modulates irak4
Salts and solid forms of IRAK4 inhibitors address the inadequacies of existing treatments by specifically targeting IRAK4 kinase activity, providing therapeutic benefits for IRAK4-regulated diseases like IBD, SLE, and psoriasis.
Patent Information
- Application Number
- HK62026124992
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-06-30
- Filing Date
- 2026-06-18
- Publication Date
- 2026-07-31
AI Technical Summary
Current treatments for diseases regulated by IRAK4, such as inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and psoriasis, are inadequate in effectively targeting IRAK4 kinase activity.
Development of salts and solid forms of IRAK4 inhibitors to specifically target and regulate IRAK4 kinase activity, providing therapeutic benefits for these diseases.
The salts and solid forms of IRAK4 inhibitors effectively modulate IRAK4 kinase activity, offering potential therapeutic benefits for inflammatory bowel disease, systemic lupus erythematosus, and psoriasis.
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Abstract
Description
(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202480037587.5 (22) Application Date 2024.06.28 (30) Priority Data 63 / 511,597 2023.06.30 US (85) PCT International Application Entering National Phase Date 2025.12.04 (86) PCT International Application Application Data PCT / US2024 / 036172 2024.06.28 (87) PCT International Application Publication Data WO2025 / 006998 EN 2025.01.02 (71) Applicant Gilead Sciences, Inc. Address: California, USA (72) Inventors S.E. Ammann, P.C. Fung, B.T. Huang, E.M. Horstman, S. Liu, H.G. Morrison, D.A. Mundar, M.G. Yang, CY. Yu (74) Patent Agency: Beijing Liu Shen Law Firm, 11105 Patent Attorney: Qin Jian (51) Int.Cl. C07D 487 / 04 (2006.01) A61P 19 / 02 (2006.01) A61P 29 / 00 (2006.01) A61K 31 / 5025 (2006.01) (54) Invention Title: Salts and Solid Forms of Compounds Regulating IRAK4 (57) Abstract: This disclosure relates to salts and solid forms of compounds that are inhibitors of the kinase IRAK4, and their use as therapeutic agents for treating diseases, conditions, or illnesses regulated by IRAK4, such as inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), psoriasis, or rheumatoid arthritis. Claims: 5 pages Description: 59 pages Drawings: 54 pages CN 121358738 A 2026.01.16 CN 1 21 35 87 38 A
Claims
1. A crystalline form of Compound I: I， (Compound I Form I), wherein Compound I Form I is characterized by an X-ray powder diffraction pattern comprising peaks at 7.5°, 12.3° and 7.2° 2Q (±0.2°) as determined on a diffractometer using Cu-Ka radiation.
2. The crystalline form of claim 1, further characterized by: i) one or more peaks at 19.1° 2Q ± 0.2°, 22.7° ± 0.2° or 15.1° ± 0.2°; ii) a diffractogram substantially as shown in FIG. 1; iii) a differential scanning calorimetry (DSC) curve comprising an endothermic peak at about 155.3 °C (onset temperature) and an endothermic peak at about 174.7 °C (onset temperature); iv) a differential scanning calorimetry (DSC) curve substantially as shown in FIG. 2; v) a thermogravimetric analysis (TGA) showing a weight loss of about 1.0 wt% up to about 150 °C; or vi) a thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.
3.
3. A crystalline form of Compound I: I， (Compound I Form II), wherein Compound I Form II is characterized by an X-ray powder diffraction pattern comprising peaks at 7.5°, 14.6° and 17.8° 2Q (±0.2°) as determined on a diffractometer using Cu-Ka radiation.
4. The crystalline form of claim 3, further characterized by: i) one or more peaks at 22.8° 2Q ± 0.2°, 26.7° ± 0.2° or 22.0° ± 0.2°; ii) a diffractogram substantially as shown in FIG. 4; iii) a differential scanning calorimetry (DSC) curve comprising an endothermic peak at about 190.7 °C (onset temperature); iv) a differential scanning calorimetry (DSC) curve substantially as shown in FIG. 5; v) a thermogravimetric analysis (TGA) showing a weight loss of about 1.0 wt% up to about 200 °C; or vi) a thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.
6.
5. A crystalline form of Compound I: I， (Compound I Form IV), wherein Compound I Form IV is characterized by an X-ray powder diffraction pattern comprising peaks at 10.1°, 10.7° and 17.9° 2Q (±0.2°) as determined on a diffractometer using Cu-Ka radiation.
6. The crystalline form of claim 5, further characterized by: i) one or more peaks at 17.3° 2Q ± 0.2°, 11.7° ± 0.2° or 21.7° ± 0.2°; ii) a diffractogram substantially as shown in FIG. 8; iii) a differential scanning calorimetry (DSC) curve comprising an endothermic peak at about 192.0 °C (onset temperature); iv) a differential scanning calorimetry (DSC) curve substantially as shown in FIG. 9; v) a thermogravimetric analysis (TGA) showing a weight loss of about 0.8 wt% up to about 200 °C; vi) a thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG. 10; or vii) a dynamic vapor sorption (DVS) profile substantially as shown in Figure 15.
7. A crystalline form of Compound I: I， (Form V of Compound I), wherein Form V of Compound I is a monohydrate and is characterized by an X-ray powder diffraction pattern comprising peaks at 11.8°, 25.9° and 20.7° 2Q (±0.2°) determined on a diffractometer using Cu-Ka radiation.
8. The crystalline form of claim 7, further characterized by: i) one or more peaks at 16.8° 2Q ± 0.2°, 23.1° ± 0.2° or 18.5° ± 0.2°; ii) a diffractogram substantially as shown in Figure 12; iii) a differential scanning calorimetry (DSC) profile comprising an endothermic peak at about 70.5 °C (onset temperature), an endothermic peak at about 151.6 °C (onset temperature) and an endothermic peak at about 189.1 °C (onset temperature); iv) a differential scanning calorimetry (DSC) profile substantially as shown in Figure 13; v) a thermogravimetric analysis (TGA) showing a weight loss of about 3.6 wt% up to about 100 °C; vi) a thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in Figure 14; or vii) a dynamic vapor sorption (DVS) profile substantially as shown in Figure 15.
9. The crystalline form of claim 7, comprising about 1 molar equivalent of water.
10. A crystalline form of Compound I: I， (Form VI of Compound I), wherein Form VI of Compound I is a monohydrate and is characterized by an X-ray powder diffraction pattern comprising peaks at 4.9°, 5.6° and 7.4° 2Q (±0.2°) determined on a diffractometer using Cu-Ka radiation.
11. The crystalline form of claim 10, further characterized by: i) one or more peaks at 8.4° 2Q ± 0.2°, 12.3° ± 0.2° or 27.2° ± 0.2°; ii) a diffractogram substantially as shown in Figure 16; iii) a differential scanning calorimetry (DSC) profile comprising an endothermic peak at about 47.0 °C (onset temperature), an endothermic peak at about 111.1 °C (onset temperature) and an endothermic peak at about 122.9 °C (onset temperature); iii) a differential scanning calorimetry (DSC) profile substantially as shown in Figure 17; v) a thermogravimetric analysis (TGA) showing a weight loss of about 5.2 wt% up to about 140 °C; vi) a thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in Figure 18; or vii) a dynamic vapor sorption (DVS) profile substantially as shown in Figure 19.
12. The crystalline form of claim 10, comprising about 1.25 molar equivalents of water.
13. A crystalline form of Compound I monolactate: I， Compound I monolactate Form I, wherein Compound I monolactate Form I is characterized by an X-ray powder diffraction pattern comprising peaks at 5.7°, 7.0° and 22.7° 2Q (±0.2°) determined on a diffractometer using Cu-Ka radiation.
14. The crystalline form of claim 13, further characterized by: i) one or more peaks at 19.6° 2Q ± 0.2°, 15.6° ± 0.2°, or 8.1° ± 0.2°; ii) a diffractogram substantially as shown in Figure 39; iii) a differential scanning calorimetry (DSC) curve comprising an endothermic peak at about 145.2 °C (onset temperature) and an endothermic peak at about 186.6 °C (onset temperature); iv) a differential scanning calorimetry (DSC) curve substantially as shown in Figure 40; v) a thermogravimetric analysis (TGA) showing a weight loss of about 0.6 wt% up to about 150 °C; vi) a thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in Figure 41 ; vii) a dynamic vapor sorption (DVS) curve substantially as shown in Figure 42.
15. The crystalline form of claim 13, comprising about 1 molar equivalent of citric acid.
16. A crystalline form of Compound I: I， Compound I Form III, wherein Compound I Form III is characterized by an X-ray powder diffraction pattern comprising peaks (± 0.2°) at 21.2°, 12.3°, and 10.7° 2Q, as determined on a diffractometer using Cu-Ka radiation; or (Form VII of Compound I), wherein Form VII of Compound I is a water: tetrahydrofuran (THF) solvate, and which is characterized by an X-ray powder diffraction pattern comprising peaks (± 0.2°) at 4.0°, 25.8°, and 6.9° 2Q, as determined on a diffractometer using Cu-Ka radiation; or Compound I Form VIII, wherein Compound I Form VIII is a water:acetonitrile (ACN) solvate, and is characterized by an X-ray powder diffraction pattern comprising peaks (± 0.2°) at 8.0°, 25.8°, and 6.1° 2Q, as determined on a diffractometer using Cu-Ka radiation; or Compound I Form IX, wherein Compound I Form IX is a water:2-methyltetrahydrofuran (Me-THF) solvate, and is characterized by an X-ray powder diffraction pattern comprising peaks (± 0.2°) at 9.4°, 4.5°, and 18.3° 2Q, as determined on a diffractometer using Cu-Ka radiation; or Compound I Form X, wherein Compound I Form X is an isopropanol (IPA) solvate, and is characterized by an X-ray powder diffraction pattern comprising peaks (± 0.2°) at 4.0°, 7.0°, and 8.2° 2Q, as determined on a diffractometer using Cu-Ka radiation; or Compound I Form XI, wherein Compound I Form XI is a methyl isobutyl ketone (MIBK) solvate, and is characterized by an X-ray powder diffraction pattern comprising peaks (± 0.2°) at 4.0°, 6.9°, and 14.5° 2Q, as determined on a diffractometer using Cu-Ka radiation; or Compound I Form XII, wherein Compound I Form XII is characterized by an X-ray powder diffraction pattern comprising peaks (± 0.2°) at 7.7°, 11.7°, and 26.1° 2Q, as determined on a diffractometer using Cu-Ka radiation; or (Form XIII of Compound I), wherein Form XIII of Compound I is characterized by an X-ray powder diffraction pattern comprising peaks at 7.6°, 14.6° and 17.9° 2Q (+ 0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form II of Compound I monolactate), wherein Form II of Compound I monolactate is a monolactate salt, and is characterized by an X-ray powder diffraction pattern comprising peaks at 5.6°, 7.0° and 24.2° 2Q (+ 0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form III of Compound I monolactate), wherein Form III of Compound I monolactate is a monolactate salt, and is characterized by an X-ray powder diffraction pattern comprising peaks at 6.3°, 18.8° and 7.7° 2Q (+ 0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form IV of Compound I monolactate), wherein Form IV of Compound I monolactate is a monolactate salt, and is characterized by an X-ray powder diffraction pattern comprising peaks at 26.8°, 25.7° and 25.1° 2Q (+ 0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I hemilactate), wherein Form I of Compound I hemilactate is a hemilactate salt, and is characterized by an X-ray powder diffraction pattern comprising peaks at 6.1°, 7.4° and 17.1° 2Q (+ 0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I monohydrochloride), wherein Form I of Compound I monohydrochloride is a monohydrochloride (HC1) salt, and is characterized by an X-ray powder diffraction pattern comprising peaks at 6.9°, 20.7° and 16.9° 2Q (+ 0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I monomaleate), wherein Form I of Compound I monomaleate is a monomaleate salt, and is characterized by an X-ray powder diffraction pattern comprising peaks at 7.4°, 6.1° and 23.2° 2Q (+ 0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I hemifumarate), wherein Form I of Compound I hemifumarate is a hemifumarate salt, and is characterized by an X-ray powder diffraction pattern comprising peaks at 7.7°, 6.8° and 13.0° 2Q (+ 0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I monofumarate), wherein Form I of Compound I monofumarate is a monofumarate salt, and is characterized by an X-ray powder diffraction pattern comprising peaks at 6.1°, 7.8° and 18.7° 2Q (+ 0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I hemi-L-tartrate), wherein Form I of Compound I hemi-L-tartrate is a hemi-L-tartrate salt and is characterized by an X-ray powder diffraction pattern comprising peaks at 8.5°, 5.2° and 18.6° 2Q (±0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I mono-ESA), wherein Form I of Compound I mono-ethanesulfonic acid (ESA) is a mono-ESA salt and is characterized by an X-ray powder diffraction pattern comprising peaks at 6.4°, 10.9° and 19.0° 2Q (±0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I hemi-glycolate), wherein Form I of Compound I hemi-glycolate is a hemi-glycolate salt and is characterized by an X-ray powder diffraction pattern comprising peaks at 6.2°, 8.0° and 22.9° 2Q (±0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I sulfate), wherein Form I of Compound I sulfate is a sulfate salt and is characterized by an X-ray powder diffraction pattern comprising peaks at 5.5°, 4.9° and 11.1° 2Q (±0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I phosphate), wherein Form I of Compound I phosphate is a phosphate salt and is characterized by an X-ray powder diffraction pattern comprising peaks at 4.8°, 9.7° and 16.9° 2Q (±0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I hemi-HCl), wherein Form I of Compound I hemi-hydrochloric acid (HCl) is a hemi-HCl salt and is characterized by an X-ray powder diffraction pattern comprising peaks at 5.6°, 9.2° and 11.2° 2Q (±0.2°) as determined on a diffractometer using Cu-Ka radiation; or (Form I of Compound I co-crystal), wherein Form I of Compound I co-crystal is a co-crystal of Compound I and 4-(((S)-1-cyanoethyl)amino)-6-(3-cyanopyrrolo[l,2-b]pyridazin-7-yl)-N-((R)-2-fluoro-3-hydroxy-3-methylbutyl)nicotinamide and is characterized by an X-ray powder diffraction pattern comprising peaks at 19.1°, 10.3° and 9.4° 2Q (±0.2°) as determined on a diffractometer using Cu-Ka radiation.
17. A pharmaceutical composition comprising a crystalline form according to any one of claims 1 to 16 and a pharmaceutically acceptable carrier.
18. A method of treating an inflammatory condition in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a crystalline form according to any one of claims 1 to 16 or a pharmaceutical composition according to claim 17.
19. The method of claim 18, wherein the inflammatory condition is selected from inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis.
20. The method of claim 19, wherein the inflammatory condition is IBD.
21. The method of claim 19, wherein the inflammatory condition is rheumatoid arthritis.