RU2021134261A - SOLID FORM OF DIAMINOPYRIMIDINE OR ITS HYDRATE, METHOD FOR ITS OBTAINING AND ITS APPLICATION - Google Patents

Claims (31)

1. Crystal form I of compound A anhydrate:

crystalline form I has XRD (powder x-ray diffraction) containing characteristic peaks located at diffraction angles (2θ) equal to about 11.9±0.2°, 12.3±0.2°, 13.9±0.2° , 19.8±0.2° and 20.3±0.2°, preferably containing characteristic peaks located at diffraction angles (2θ) of about 10.1±0.2°, 11.9±0.2 °, 12.3±0.2°, 13.9±0.2°, 17.8±0.2°, 18.6±0.2°, 19.8±0.2° and 20.3 ±0.2°, and most preferably containing characteristic peaks located at diffraction angles (2θ) of about 6.2±0.2°, 10.1±0.2°, 11.9±0.2°, 12.3±0.2°, 13.9±0.2°, 16.9±0.2°, 17.8±0.2°, 18.6±0.2°, 19.8±0 .2°, 20.3±0.2°, 21.8±0.2°, 23.0±0.2°, 23.6±0.2°, 24.1±0.2°, 26 .2±0.2°, 26.5±0.2°, 27.8±0.2°, 28.5±0.2°, 29.3±0.2° and 30.6±0, 2°. 2. A method for obtaining crystalline form I of an anhydrate of compound A according to claim 1, including the following stages: 1) adding compound A to water, then adding acid, stirring to dissolve compound A and obtaining a solution, which is optionally filtered and a filtrate is obtained; 2) adding base to the solution or filtrate obtained in step 1), and collecting the precipitated solid by filtration; And 3) adding the resulting solid to water and mixing, filtering to collect the solid, which is optionally dried to give crystalline Form I; alternatively, the method comprises dissolving Compound A in a good solvent to form a solution, then adding an anti-solvent to the solution, and stirring to allow a solid to precipitate, which is filtered and a crystalline form is obtained. 3. Crystal form II of compound A monohydrate:

crystalline Form II has an XXRD containing characteristic peaks located at diffraction angles (2θ) of about 13.0±0.2°, 19.5±0.2°, and 19.9±0.2°, preferably containing characteristic peaks located at diffraction angles (2θ) of about 9.6±0.2°, 13.0±0.2°, 19.5±0.2°, 19.9±0.2° and 22, 7±0.2°, and most preferably containing characteristic peaks located at diffraction angles (2θ) of about 9.6±0.2°, 10.9±0.2°, 13.0±0.2° , 14.9±0.2°, 15.8±0.2°, 16.8±0.2°, 19.5±0.2°, 19.9±0.2°, 22.7± 0.2°, 23.7±0.2°, 25.2±0.2°, 26.0±0.2°, 28.5±0.2°, 29.0±0.2°, 30.0±0.2° and 32.5±0.2°. 4. Crystal form III of compound A hemihydrate:

crystalline Form III has an XXRD containing characteristic peaks located at diffraction angles (2θ) of about 10.8±0.2° and 20.5±0.2°, preferably containing characteristic peaks located at diffraction angles (2θ) equal to approximately 10.8±0.2°, 19.3±0.2°, 20.5±0.2°, 21.7±0.2° and 26.9±0.2°, and most preferably containing characteristic peaks located at diffraction angles (2θ) of about 10.8±0.2°, 13.0±0.2°, 15.0±0.2°, 15.4±0.2° , 16.5±0.2°, 17.3±0.2°, 19.3±0.2°, 19.9±0.2°, 20.5±0.2°, 21.7± 0.2°, 23.3±0.2°, 25.1±0.2°, 26.5±0.2°, 26.9±0.2°, 28.7±0.2° and 32.2±0.2°. 5. Crystal form IV of compound A sesquihydrate:

crystalline Form IV has an XXRD containing characteristic peaks located at diffraction angles (2θ) of about 12.3±0.2°, 21.3±0.2°, and 24.1±0.2°, preferably containing characteristic peaks located at diffraction angles (2θ) equal to about 12.3±0.2°, 12.6±0.2°, 17.2±0.2°, 20.0±0.2°, 20, 6±0.2°, 21.3±0.2°, 23.8±0.2°, 24.1±0.2°, 25.0±0.2° and 27.9±0.2 °, and most preferably containing characteristic peaks located at diffraction angles (2θ) equal to about 12.3±0.2°, 12.6±0.2°, 14.3±0.2°, 17.2± 0.2°, 20.0±0.2°, 20.6±0.2°, 21.3±0.2°, 23.2±0.2°, 23.8±0.2°, 24.1±0.2°, 25.0±0.2°, 25.7±0.2°, 27.9±0.2°, 31.2±0.2° and 31.7±0 .2°. 6. Crystal form V of compound A monohydrate:

crystalline Form V has an XXRD containing characteristic peaks located at diffraction angles (2θ) of about 14.1±0.2°, 21.0±0.2°, and 29.6±0.2°, preferably containing characteristic peaks located at diffraction angles (2θ) equal to about 8.7±0.2°, 9.4±0.2°, 11.9±0.2°, 14.1±0.2°, 15, 8±0.2°, 16.8±0.2°, 18.9±0.2°, 19.9±0.2°, 20.6±0.2°, 21.0±0.2 °, 22.5 ± 0.2 ° and 29.6 ± 0.2 °, and most preferably containing characteristic peaks located at diffraction angles (2θ) equal to approximately 8.7 ± 0.2 °, 9.4 ± 0.2°, 11.6±0.2°, 11.9±0.2°, 12.4±0.2°, 14.1±0.2°, 14.5±0.2°, 15.8±0.2°, 16.2±0.2°, 16.8±0.2°, 17.6±0.2°, 18.2±0.2°, 18.9±0 .2°, 19.9±0.2°, 20.6±0.2°, 21.0±0.2°, 22.5±0.2°, 23.0±0.2°, 23 .6±0.2°, 24.4±0.2°, 25.2±0.2°, 27.0±0.2° and 29.6±0.2°. 7. Crystal form VI of compound A monohydrate:

crystalline form VI has an XXRD containing characteristic peaks located at diffraction angles (2θ) of about 10.4±0.2°, 12.1±0.2°, 16.6±0.2°, 20.7 ±0.2°, 22.8±0.2° and 27.3±0.2°, preferably containing characteristic peaks located at diffraction angles (2θ) of about 8.7±0.2°, 10, 4±0.2°, 12.1±0.2°, 15.4±0.2°, 16.6±0.2°, 19.5±0.2°, 20.7±0.2 °, 21.2±0.2°, 22.8±0.2°, and 27.3±0.2°, and most preferably containing characteristic peaks located at diffraction angles (2θ) of about 8.7± 0.2°, 10.4±0.2°, 12.1±0.2°, 13.4±0.2°, 14.7±0.2°, 15.4±0.2°, 16.6±0.2°, 17.4±0.2°, 19.5±0.2°, 20.7±0.2°, 21.2±0.2°, 22.1±0 .2°, 22.8±0.2°, 23.6±0.2°, 26.0±0.2°, 27.3±0.2°, 28.0±0.2° and 30 .4±0.2°. 8. Crystalline form VII of compound A sesquihydrate:

crystalline Form VII has an XXRD containing characteristic peaks located at diffraction angles (2θ) of about 13.1±0.2°, 19.9±0.2°, and 20.2±0.2°, preferably containing characteristic peaks located at diffraction angles (2θ) equal to about 13.1±0.2°, 16.9±0.2°, 19.9±0.2°, 20.2±0.2°, 24, 9±0.2° and 28.8±0.2°, and most preferably containing characteristic peaks located at diffraction angles (2θ) of about 9.4±0.2°, 10.8±0.2° , 13.1±0.2°, 15.4±0.2°, 16.9±0.2°, 18.8±0.2°, 19.9±0.2°, 20.2± 0.2°, 22.2±0.2°, 23.2±0.2°, 24.9±0.2°, 26.4±0.2° and 28.8±0.2°. 9. Crystal form VIII hemihydrate compound A:

crystalline Form VIII has an XXRD containing characteristic peaks located at diffraction angles (2θ) of about 13.0±0.2°, 16.8±0.2°, 19.4±0.2°, 21.7 ±0.2°, 22.9±0.2° and 27.4±0.2°, preferably containing characteristic peaks located at diffraction angles (2θ) of about 10.3±0.2°, 13, 0±0.2°, 16.8±0.2°, 19.1±0.2°, 19.4±0.2°, 21.1±0.2°, 21.7±0.2 °, 22.9±0.2°, 25.8±0.2°, and 27.4±0.2°, and most preferably containing characteristic peaks located at diffraction angles (2θ) of about 8.7± 0.2°, 10.3±0.2°, 10.8±0.2°, 13.0±0.2°, 14.1±0.2°, 14.8±0.2°, 16.8±0.2°, 17.5±0.2°, 19.1±0.2°, 19.4±0.2°, 21.1±0.2°, 21.7±0 .2°, 22.3±0.2°, 22.9±0.2°, 25.8±0.2°, 27.4±0.2°, 27.8±0.2°, 30 .4±0.2° and 31.6±0.2°. 10. Pharmaceutical composition containing crystalline form I according to claim 1, crystalline form II according to item 3, crystalline form III according to item 4, crystalline form IV according to item 5, crystalline form V according to item 6, crystalline form VI according to claim 7, crystalline form VII according to claim 8 or crystalline form VIII according to claim 9, and one or more pharmaceutically acceptable carriers. 11. The use of crystal form I according to claim 1, crystal form II according to claim 3, crystal form III according to claim 4, crystal form IV according to claim 5, crystal form V according to claim 6, to crystal form VI according to claim 7, crystalline form VII according to claim 8 or crystalline form VIII according to claim 9 for the preparation of a medicament for the prevention or treatment of a disease mediated by a P2X3 and/or P2X2/3 receptor antagonist; preferably a disease selected from the group consisting of the following urinary tract disease selected from the following: decreased bladder capacity, frequent urination, urge incontinence, stress incontinence, overactive bladder, benign prostatic hypertrophy, prostatitis, detrusor hyperreflexia , nocturia, urinary urgency, pelvic hypersensitivity, urethritis, pelvic pain syndrome, prostatodynia, cystitis, and idiopathic bladder hypersensitivity; pain selected from the following: inflammatory pain, surgical pain, visceral pain, toothache, premenstrual pain, central pain, pain caused by burns, migraine and severe paroxysmal headache with periodic recurrences, pain with nerve damage; pain with neuritis; neuralgia; pain in case of poisoning; pain in ischemic lesions; pain with interstitial cystitis; cancer pain; pain due to a viral, parasitic or bacterial infection; post-traumatic pain and pain associated with irritable bowel syndrome; cardiovascular disease, preferably hypertension; a respiratory disease selected from among the following: chronic obstructive pulmonary disease, asthma and bronchospasm; a gastrointestinal disease selected from among the following: irritable bowel syndrome (preferably diarrhea-dominant irritable bowel syndrome), inflammatory bowel disease, hepatic colic, renal colic, and pain associated with gastrointestinal distension.