COMBINATION OF BCL-2 INHIBITOR AND MCL-1 INHIBITOR, USE AND PHARMACEUTICAL COMPOSITIONS THEREOF Russian patent published in 2021 - IPC A61K31/5377 A61K31/496 A61K31/519 A61P35/00 

FIELD: pharmaceutics.

SUBSTANCE: invention relates to the field of medicine and pharmaceutics, namely to a combination for treatment of malignant growths, comprising: (a) BCL-2 inhibitor selected from: (i) N-(4-hydroxyphenyl)-3-{6-[((3S)-3-(4-morpholinylmethyl)-3,4-dihydro-2(1H)-isoquinolinyl)carbonyl]-1,3-benzodioxol-5-yl}-N-phenyl-5,6,7,8-tetrahydro-1-indolizine carboxamide, (ii) 5-(5-chloro-2-{[(3S)-3-(morpholine-4-ylmethyl)-3,4-dihydroisoquinoline-2(1H)-yl]carbonyl}phenyl )-N-(5-cyano-1,2-dimethyl-1H-pyrrol-3-yl)-N-(4-hydroxyphenyl)-1,2-dimethyl-1H-pyrrole-3-carboxamide or salts thereof, and (iii) 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazine-1-yl)-N-[(3-nitro-4-{[(oxan-4-yl)methyl]amino}phenyl)sulfonyl]-2-[(1H-pyrrolo[2,3-b]pyridine-5-yl)oxy]benzamide (ABT-199); and (b) an MCL1 inhibitor selected from: (iv) (2R)-2-{[(5Sa)-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazine-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy}-3-(2-{[1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]methoxy}phenyl)propionic acid, and (v) (2R)-2-{[(5Sa)-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazine-1-yl)ethoxy]phenyl}-6-(4-fluorophenyl)thieno[2,3-d]pyrimidine-4-yl]oxy}-3-(2-{[2-(2-methoxyphenyl)pyrimidine-4-yl]methoxy}phenyl)propionic acid or salts thereof; and to a medicinal product containing said combination and to use thereof for treatment of malignant growths.

EFFECT: group of inventions provides a synergetic effect of the combination.

41 cl, 17 dwg, 24 tbl, 13 ex