FIELD: medicine; pharmaceuticals.
SUBSTANCE: invention relates to a novel crystalline form of a salt (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide of formula (I-HS). Compound can be used for treating a malignant tumor mediated by Trk-kinase. Crystalline form (I-HS) has basic diffraction peaks XRPD (degrees 2θ) at 18.4±0.2; 29.7±9.2; 23.1±9.2 and 24.9±0.2 and fusion heat based on DSC-thermogram values of about 2.415 mW. Mold is non-hygroscopic and demonstrates less than 2 % weight gain at 25 °C and 89 % relative humidity after 24–48 hours when determined by dynamic steam sorption. Invention also relates to versions of a method of producing the crystalline form of I-HS and versions of the method of treating a malignant tumor described in the patent claim.
EFFECT: crystalline form (I-HS) has stability during storage and use, non-hygroscopicity, improved flow characteristics, improved profile of presence of impurities, which allows to ensure safety during treatment.
27 cl, 47 dwg, 29 tbl, 11 ex
| Title | Year | Author | Number |
|---|---|---|---|
| LIQUID COMPOSITIONS (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)PYRROLIDINE-1-YL)PYRAZOLO[1,5-A]PYRIMIDINE-3-YL)-3-HYDROXYPYRROLIDINE-1-ARBOXAMIDE | 2017 |
|
RU2751767C2 |
| METHODS FOR TREATMENT OF CHILDHOOD CANCER DISEASES | 2017 |
|
RU2751636C2 |
| POINT MUTATIONS IN TRK INHIBITOR-RESISTANT MALIGNANT TUMORS AND RELATED METHODS | 2016 |
|
RU2744852C2 |
| CONDENSED AZA-HETEROCYCLIC AMIDE COMPOUND AND ITS USE | 2021 |
|
RU2811975C1 |
| SUBSTITUTED (2-AZABICYCLO[3.1.0]HEXANE-2-YL)PYRAZOLO[1.5-A]PYRIMIDINE AND IMIDAZO[1.2-B]PYRIDAZINE COMPOUNDS AS TRK KINASE INHIBITORS | 2019 |
|
RU2781618C2 |
| 1-((3S,4R)-4-(3-FLUOROPHENYL)-1-(2-METHOXYETHYL)PYRROLIDIN-3-YL)-3-(4-METHYL-3-(2-METHYLPYRIMIDIN-5-YL)-1-PHENYL-1N-PYRAZOL-5-YL)UREA AS A TRKA KINASE INHIBITOR | 2015 |
|
RU2719489C2 |
| CHIRAL DIARYL MACROCYCLES AND USE THEREOF | 2016 |
|
RU2728579C2 |
| AMINOPYRAZOLOPYRIMIDINE COMPOUND USED AS INHIBITOR OF TYROSINE KINASE RECEPTOR OF NEUROTROPHIC FACTOR | 2017 |
|
RU2764523C2 |
| COMPOSITION OF COMPOUNDS AND WAYS OF THEIR APPLICATION | 2015 |
|
RU2659068C1 |
| SUBSTITUTED PYRAZOLO[1,5-A]PYRIMIDINE COMPOUNDS AS INHIBITORS OF TRK KINASE | 2014 |
|
RU2666367C2 |
