LIQUID COMPOSITIONS (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)PYRROLIDINE-1-YL)PYRAZOLO[1,5-A]PYRIMIDINE-3-YL)-3-HYDROXYPYRROLIDINE-1-ARBOXAMIDE Russian patent published in 2021 - IPC C07D487/04 A61K31/519 A61P35/00 

FIELD: biochemistry.

SUBSTANCE: invention relates to liquid formulations for the treatment of cancer associated with TRK. In one embodiment, the liquid formulation contains (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), a pharmaceutically acceptable salt thereof, or a combination thereof; hydroxypropy-β-cyclodextrin, sodium citrate and sweetener, where the pH of the specified composition is from 2.5 to 5.5, and the concentration of the compound of formula (I), its pharmaceutically acceptable salt or their combination in the liquid composition is from 20 mg/ml to 30 mg/ml. In another embodiment, the liquid formulation contains (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), a pharmaceutically acceptable salt thereof, or a combination thereof; hydroxypropyl - cyclodextrin in an amount from 13 wt % to 17 wt %; sodium citrate dihydrate in an amount from 0.7 wt % to 1.5 wt %; a sweetener that includes sucrose, glycerin, sorbitol, and a flavoring agent, the sweetener being contained in a citric acid sodium phosphate buffer; wherein the sweetener is conserved with methylparaben and potassium sorbate, and wherein the sweetener is contained in an amount from 45 wt % to 55 wt %; and a bitterness masking agent, which is contained in the liquid composition in an amount of 0.2 wt % to 0.5 wt %; while the pH of the specified composition is from 2.5 to 5.5; and the concentration of a compound of Formula (I), a pharmaceutically acceptable salt thereof, or a combination thereof in the said liquid formulation is from 20 mg/ml to 30 mg/ml. The invention also relates to the use of said liquid formulations for the treatment of TRK kinase mediated cancer in a patient in need thereof.

EFFECT: invention can be used in cancer treatment.

28 cl, 19 tbl, 6 ex, 13 dwg