INHIBITOR OF EGFR AND PRODUCTION AND USE THEREOF Russian patent published in 2019 - IPC C07D403/04 C07D405/14 C07D491/107 C07D487/10 C07D403/14 C07D413/14 C07D239/48 C07D471/06 C07F9/53 C07D405/12 A61K31/505 A61K31/506 A61K31/5377 A61K31/662 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a novel derivative of 4-substituted-2- (N- (5-substituted-allylamide) phenyl) -amino) pyrimidine represented by formula (I). In formula (I)

ring A is selected from a group consisting of

where Q is a bond; R is selected from a group consisting of hydrogen; X₁, X₂ and X₃ each is independently selected from a group consisting of NR₇ and CR₈, where one or two of X₁, X₂ and X₃ are NR₇, wherein, when X₂ is NR₇, other groups are CR₈, and a ring with said group X₂ is joined by a carbon atom to a pyrimidine ring, or when two of X₁, X₂ and X₃ are NR₇, ring is joined by nitrogen atom of said group to pyrimidine ring; R₁ is selected from the group consisting of:

wherein three R₆ in are optionally identical or different substitutes; R₂ is selected from a group consisting of C_1-8 alkyl, where C_1-8 alkyl is optionally substituted with one or more groups selected from a group consisting of halogen; R₃ is selected from a group consisting of hydrogen, halogen, trifluoromethyl, trifluoromethoxy and P(O)R₁₁R₁₂, where R₁₁R₁₂ are C_1-6 alkyl; R₄ are independently selected from a group consisting of hydrogen, halogen, cyano, C_1-8 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, C_3-8 cycloalkyl, 4-membered saturated heterocyclyl containing an oxygen atom in the cycle, -P(O)R₁₁R₁₂, where R₁₁R₁₂ are represented by C_1-6 alkyl, -S(O)rR₉, -OR₁₀, -C(O)R₁₀, where C_1-8 alkyl is optionally substituted with one or more groups selected from a group consisting of halogen, hydroxy and -OR₁₀; R₆ is selected from a group consisting of hydrogen and C_1-8 alkyl; R₇ is selected from a group consisting of C_1-8 alkyl, C_2-8 alkenyl, C_3-6 cycloalkyl, -S(O)rR₉, -OR₁₀, -C(O)R₁₀ and 4-member saturated heterocyclyl containing an oxygen atom in a cycle; where C_1-8 alkyl is substituted with one or more groups selected from a group consisting of hydroxy, C_2-8 alkenyl and C_2-8 alkynyl; R₈ is selected from a group consisting of hydrogen, C_1-8 alkyl, C_3-8 cycloalkyl and -OR₁₀; R₉ is selected from a group consisting of bis-C_1-8 alkylamino; R₁₀ is selected from a group consisting of C_1-8 alkyl and C_3-8 cycloalkyl; m equals 0, 1, 2; r is equal to 2; o equals 0; p equals 1; q equals 1. Method of producing compound I is carried out according to the following scheme

where ring A, Q, X₁, X₂, X₃, R, R₁, R₂, R₃, R₄, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, m, r, o, p and q are as defined above.

EFFECT: compounds have the properties of an EGFR inhibitor of a mutant type, in particular a mutant EGFR-T790M, and can be used to treat a cell proliferation-mediated disease mediated by EGFR-T790M mutant activity; such disease can be cancer, which can be selected from a group consisting of ovarian cancer, cervical cancer, colorectal cancer, breast cancer, pancreatic cancer, glioma, glioblastoma, melanoma, prostate cancer, leukemia, lymphoma, non-Hodgkin lymphoma, stomach cancer, lung cancer, hepatocellular carcinoma, gastric cancer, gastrointestinal stromal tumor (GIST), thyroid cancer, cholangiocarcinoma, endometrial cancer, kidney cancer, anaplastic large cell lymphoma, acute myeloid leukemia (AML), multiple myeloma, melanoma and mesothelioma; preferably non-small cell lung cancer.

36 cl, 6 tbl, 143 ex