PTERIDINES AS FGFR INHIBITORS Russian patent published in 2019 - IPC C07D475/08 A61K31/519 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a novel pteridine derivative of formula (I), including any stereochemically isomeric form thereof and a pharmaceutically acceptable salt thereof. In particular, the compounds can be used in treating or preventing cancer selected from prostate cancer, bladder cancer, lung cancer, such as non-small cell lung carcinoma, breast cancer, stomach cancer and liver cancer, multiple myeloma, myeloproliferative disorders, endometrial cancer, ovarian cancer, colorectal cancer and squamous cell carcinoma of the oral cavity. Compounds can be used, for example, in treating bladder cancer, with translocation of FGFR3 chromosomes and with a point mutation FGFR3. Cancer can be a tumour with mutations FGFR1, FGFR2, FGFR3 or FGFR4, in particular mutant FGFR2 or FGFR3 with the acquisition of a new function or with overexpression of FGFR1. In formula (I)

W is -N(R³) -; each R² is independently selected from halogen and C_1-4alkoxy; D is phenyl or 5-member aromatic monocyclic heterocyclyl containing two heteroatoms of nitrogen, where each said phenyl and heterocyclyl can optionally be substituted with one group R¹; R¹ is hydrogen or C_1-6alkyl; R³ is halo C_1-6alkyl, hydroxyC_1-6alkyl, C_1-6alkyl substituted with R⁹, C_1-6alkyl substituted with -NR¹⁰R¹¹; R⁹ is C_3-8cycloalkyl or 5-member monocyclic unsaturated or saturated heterocyclyl containing one or two heteroatoms of nitrogen, where each said C_3-8cycloalkyl or 5-member monocyclic heterocyclyl, and each is independently substituted with 1 substituent selected from = O, C_1-4alkyl and -S(=O)₂-NR¹⁴R¹⁵; each R¹⁰ and R¹¹ independently represents hydrogen or C_1-6alkyl; each R¹⁴ and R¹⁵ independently represent hydrogen or C_1-4alkyl; n independently represents an integer equal to 0, 1, 2, 3 or 4.

EFFECT: compounds have the properties of a FGFR kinase inhibitor and can be used to treat a disease or condition mediated by FGFR kinase, particularly cancer.

27 cl, 1 tbl, 4 ex