MENIN-MLL INTERACTION INHIBITORS Russian patent published in 2023 - IPC C07D405/14 C07D403/04 C07D403/14 C07D471/10 C07D487/10 C07D491/10 A61K31/407 A61K31/506 A61K31/4427 A61K31/5377 A61P35/00 A61P3/10 

FIELD: medicine.

SUBSTANCE: invention relates to a compound of the formula I or to its pharmaceutically acceptable salt, where each A, B, D, and E is independently selected from -C(R^A1)(R^A2)-, -C(R^A1)(R^A2)-C(R^A1)(R^A2)-, -C(R^A1)(R^A2)-O-, -C(R^A1)(R^A2)-NR^A3-, -C(=O)-, -C(R^A1)(R^A2)-C(=O)-, and -N=C(NH₂)-, where at most one of A, B, D, and E is -C(R^A1)(R^A2)-O-, -C(R^A1)(R^A2)-NR^A3-, -C(R^A1)(R^A2)-C(=O)-, -C(=O)-, or -N=C(NH₂)-; U is N or CR^U, where R^U is H; W is N or CR^W, where R^W is H; X is N or CR^X, where R^X is H, OH, or amino, wherein, if X is N, then atom L, which is directly related to X, is different from N; L is selected from -C_1-6alkylene- and -(C_1-4alkylene)_a-Q-(C_1-4alkylene)_b-, where C_1-6alkylene group and any of C_1-4alkylene groups of -(C_1-4alkylene)_a-Q-(C_1-4alkylene)_b-group is optionally substituted with 1 substitute selected from C_1-3alkyl and amino; Q is -C(=O)- or -NR^q1-, where each R^q1 is independently selected from H or C_1-6alkyl; Cy is binding C_6-10aryl, C_3-10cycloalkyl, 5-10-element heteroaryl group containing 1-3 heteroatoms, or 5-10-element heterocycloalkyl group containing 1-2 heteroatoms, each of which is optionally substituted with 1, 2, or 3 substitutes independently selected from R^Cy; each R^Cy is independently selected from halogen, C_1-6alkyl, 5-element heterocycloalkyl containing 1-2 heteroatoms selected from N and O, CN, OR^a1, C(O)NR^c1R^d1, C(O)OR^a1, NR^c1R^d1, NR^c1C(O)R^b1, NR^c1C(O)OR^a1, NR^c1C(O)NR^c1R^d1, NR^c1S(O)₂R^b1, S(O)₂R^b1, and S(O)₂NR^c1R^d1, where each specified C_1-6alkyl is optionally substituted with 1 substitute independently selected from OR^a1, NR^c1R^d1, and NR^c1C(O)R^b1; R¹ is H, C_1-6alkyl, OR^a2, C(O)OR^a2, NR^c2R^d2; Y is O, CR^Y1R^Y2, or NR^Y3, where R^Y1, R^Y2, and R^Y3 are H; Z is Cy², halogen, C_1-6alkyl, OR^a3, C(O)R^b3, C(O)NR^c3R^d3, NR^c3C(O)R^b3, NR^c3C(O)OR^a3, NR^c3S(O)₂R^b3, S(O)₂NR^c3R^d3, and P(O)R^c3R^d3, where each specified C_1-6alkyl is optionally substituted with 1 or 2 substitutes independently selected from Cy², halogen, CN, OR^a3, NR^c3R^d3, NR^c3C(O)R^b3; each R² and R³ are independently selected from H, halogen, and C_1-6alkyl; each R^A1 is independently selected from H, amino, and OH; each R^A2 is independently selected from H and OH; each R^A3 is independently selected from H and C_1-4alkyl, where the specified C_1-4alkyl is optionally substituted with OH; each Cy² is independently selected from C₆aryl, C_3-10cycloalkyl, 5-6-element heteroaryl containing 1-2 heteroatoms, and 10-element heterocycloalkyl containing 1-2 heteroatoms, each of which is optionally substituted with 1, 2, or 3 substitutes independently selected from R^Cy2; each R^Cy2 is independently selected from halogen, C_1-6alkyl, C_1-4halogenalkyl, C_1-4cyanoalkyl, C_2-6alkenyl, C_3-7cycloalkyl, CN, C(O)NR^c5R^d5, C(O)OR^a5, where each specified C_1-6alkyl is optionally substituted with 1 substitute independently selected from OR^a5; each R^a1, R^b1, R^c1, R^d1, R^a3, R^b3, R^c3, R^d3, R^a5, R^c5, and R^d5 is independently selected from H, C_1-6alkyl, C_1-4haloalkyl, C₆aryl, C_3-10cycloalkyl, 5-6-element heterocycloalkyl containing 1-2 heteroatoms, C_6-10aryl-C_1-6alkyl, C_3-6cycloalkyl-C_1-6alkyl, where each specified C_1-6alkyl is optionally substituted with 1 or 2 substitutes independently selected from R^g; each R^g is independently selected from a group consisting of OH, C_1-6alkyl, and aminocarbonyl; n is 0 or 1; m is 0 or 1; p is 0 or 1; q is 0 or 1; a is 0 or 1; and b is 0, where any cycloalkyl or heterocycloalkyl group is optionally additionally substituted with 1 oxogroup; and where cycloalkyl is a mono- or bicyclic ring system, in which one ring is cycloalkyl, which may optionally contain one unsaturated element as part of the ring structure, where bicyclic cycloalkyl includes condensed systems and spirocycles; where the condensed ring may be an aromatic ring or a non-aromatic ring; where heterocycloalkyl is a mono- or bicyclic ring system, in which one ring is a non-aromatic heterocyclic ring system, which may optionally contain one or two unsaturated elements as part of the ring structure, and which contains at least one heteroatom in the ring, independently selected from nitrogen and oxygen, where bicyclic heterocycloalkyl includes condensed systems and spirocycles; where the condensed ring may be an aromatic ring or a non-aromatic ring. The invention also relates to methods for inhibition of interaction between menin and MLL based on the specified compound of the formula I.

EFFECT: new compounds are obtained, which can be used in medicine for the treatment of malignant tumors and other diseases mediated by menin-MLL interaction.

44 cl, 23 dwg, 30 tbl, 267 ex