SUBSTITUTED COMPOUNDS OF PYRAZOLE[1,5-a]PYRIMIDINE AS TRK KINASE INHIBITORS Russian patent published in 2016 - IPC C07D487/04 C07D519/00 A61K31/519 A61P35/00 A61P29/00 A61P17/00 A61P31/00 

FIELD: biotechnology.

SUBSTANCE: invention relates to a compound having the general formula

,

or its pharmaceutically acceptable salt, where R¹ is H or (1-6C alkyl); R² is H, (1-6C)alkyl, -(1-6C) fluoroalkyl, -(1-6C)difluoroalkyl, -(1-6C)trifluoroalkyl, -(1-6C)chloralkyl, -(2-6C)chlorfluoroalkyl, -(2-6C)chlorhydroxyalkyl, -(1-6C)hydroxyalkyl, -(2-6C)dihydroxyalkyl, -(1-6C alkyl)CN, -(1-6C alkyl) SO₂NH₂, -(1-6C alkyl)NHSO₂(1-3C alkyl), -(1-6C alkyl)NH₂, -(1-6C alkyl)NHC(= O)O(1-4C alkyl), -(1-6C alkyl) getSus¹, -(1- 6C alkyl)getAr¹, getAr², getSus², -O(1-6C alkyl), which is optionally substituted by halogen, OH or (1-4C)alkoxy, Sus¹, -(1-6C alkyl)(3-6C cycloalkyl), -(1-6C alkyl)(1-4C alkoxy), -(1-6C hydroxyalkyl)(1-4C alkoxy) with bridged 7-membered cycloalkyl ring optionally substituted with (1-6C)hydroxyalkyl, or bridged 7-8-membered heterocyclic ring having 1-2 ring nitrogen atoms; or NR¹R² forms a 4-6-membered azacyclic ring optionally substituted with one or more substituents independently selected from (1-6C)alkyl, OH, CO₂H, (1-3C alkyl)CO₂H, -O(1-6C alkyl) and (1-6C)hydroxyalkyl; Y is (i) phenyl optionally substituted with one or more substituents independently selected from halogen, (1-4C)alkoxy, -CF₃ -O(1-4C alkyl)getSus³, -(1-4C alkyl)getSus³, -O(1-4C alkyl)O(1-3C alkyl) and -O(3-6C dihydroxyalkyl), or (ii) pyridyl, where the said pyridyl is optionally substituted with one or more substituents independently selected from halogen, -O(1-4C alkyl), (1-4C) alkyl and NH₂, or (iii) pyrid-2-on-3-yl ring optionally substituted by one or more substituents independently selected from halogen and (1-4C)alkyl; X is -CH₂-; R³ is H; each of R⁴ is independently selected from halogen, -(1-4C)alkyl, -OH and -CH₂OH; and n is equal to 0, 1 or 2. The invention also relates to variants of methods of preparing compounds of formula I. The invention relates to specific compounds of the formula I. The compounds are intended for use in treating pain, cancer, inflammation, neurodegenerative disease, infection of Trypanosoma cruzi or atopic dermatitis.

EFFECT: said compounds are used as inhibitors of protein tyrosine kinase of Trk family.

65 cl, 9 tbl