QUINAZOLINONE DERIVATIVES APPLICABLE AS MODULATORS OF FGFR KINASE Russian patent published in 2019 - IPC C07D239/82 C07D403/12 C07D403/04 C07D405/14 C07D405/04 C07D401/04 C07D401/14 C07D403/14 A61K31/517 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a novel quinazolinone derivative of formula (I), including any tautomeric or stereochemically isomeric form thereof, or a pharmaceutically acceptable salt thereof. Compound possesses the properties of the FGFR kinase inhibitor, in particular FGFR1, FGFR2, FGFR3 or FGFR4 or their mutations. Compounds can be used for treating cancer mediated by FGFR kinase, where the cancer is selected from multiple myeloma, including multiple myeloma with translocation t (4; 14), myeloproliferative disorders, endometrial cancer, prostate cancer, bladder cancer, lung cancer, ovarian cancer, breast cancer, gastric cancer, colon and rectum cancer and squamous cell carcinoma of the oral cavity, squamous cell carcinoma, liver cancer, renal cancer, breast cancer. In the compound of formula (I):

(I)

W is -N(R³) - or -C(R^3aR^3b) -; each R² is independently selected from halogen and C_1-4alkoxy; D is phenyl or 5–6 membered monocyclic heterocyclyl containing 1 or 2 heteroatoms selected from N or O, where each said phenyl and heterocyclyl can optionally be substituted with 1, 2 or 3 groups R¹; R¹ is hydrogen, C_1-4alkyl or -C(=O)-OC_1-6alkyl; R^3a and R^3b are combined with formation of =O or with formation of =CH-C_0-4alkyl, which is substituted with R^3c; R^3c is cyano; R³ is hydroxyC_1-6alkyl, C_1-6alkyl, which is substituted with R⁹, or C_1-6alkyl, which is substituted with -NR¹⁰R¹¹; R⁹ is 5- or 6-member monocyclic heterocyclyl containing one or two N heteroatoms, said 5- or 6-member monocyclic heterocyclyl is optionally substituted with one -S(=O)₂-NR¹⁴R¹⁵; each R¹⁰ and R¹¹ independently represents hydrogen or C_1-6alkyl; each R¹⁴ and R¹⁵ independently represents hydrogen or C_1-4alkyl; n independently represents an integer equal to 1, 2, 3 or 4.

EFFECT: treatment of cancer.

31 cl, 3 tbl, 35 ex