NOVEL COMPOUND OF 2,3,5-SUBSTITUTED THIOPHENE AS A PROTEIN KINASE INHIBITOR Russian patent published in 2020 - IPC C07D333/10 C07D409/12 A61K31/381 A61K31/4436 A61P35/00 A61P35/02 

FIELD: medicine; pharmaceuticals.

SUBSTANCE: invention can be used in pharmaceutical industry and refers to a group of compounds, pharmaceutical compositions based thereon and methods for preparing them. Disclosed is a method of producing derivative 1a, comprising obtaining compound 4 by reacting compound 2 with trimethylsilylacetylene 3:

,

obtaining compound 5 by removing the protective group from compound 4:

,

obtaining compound 7 by reacting compound 5 with halogenide 6:

,

obtaining compound 9 by reacting compound 7 with trichloroacetyl isocyanate 8:

,

obtaining compound 10 by removing trichloroacetyl group from compound 9:

,

obtaining compound 1a by removing group Boc from compound of formula 10:

,

or method involves preparing compound 7 by reacting compound 2 and compound 11:

,

obtaining compound 9 by reacting compound 7 with trichloroacetyl isocyanate 8:

,

obtaining compound 10 by removing a trichloroacetyl group from compound 9:

,

obtaining a compound of formula 1a by removing a group of Boc from compound 10:

, where R₁ is 0–2 substitutes selected from halogen, nitro, cyano, C_1-6alkyl, C_1-6haloalkyl, -C(O)OC_1-6alkyl, -S(O)₂-C_1-6alkyl, -(CH₂)_m-C_1-6alkoxy, tetrahydro-2H-pyranyl, piperidinyl, 4-(acetyl)-piperidinyl, 4-(C_1-6alkylsulphonyl)-piperidinyl, pyrrolidinyl and morpholinyl, m is from 1 to 6, R₂ is a hydrogen atom, A is phenyl, thiophenyl, indazolyl, pyridinyl, pyrimidinyl, pyrazinyl or pyrazolyl, n equals 1 to 3, X is halogen, Z is O.

EFFECT: novel compounds and pharmaceutical compositions based thereon, effective for treating, preventing and relieving acute myeloid leukemia with a FLT3 point mutation, as well as efficient methods for production thereof.

8 cl, 59 ex, 2 tbl