INHIBITORS OF MENIN-MLL INTERACTION

摘要

FIELD: chemistry.;SUBSTANCE: invention relates to a compound of formula I or a pharmaceutically acceptable salt thereof, where ring A is a group of formulas given in the claim, where e and f denote points of attachment of the remaining part of the molecule; U is N or CRU, where RU is H; group (a) is selected from (a1), (a2), (a3), (a4) or (a5), where RY is H; X is F or Cl; L is selected from -C1-6 alkylene- and -(C1-4 alkylene)a-Q-(C1-4 alkylene)b-, where C1-6 alkylene group and any C1-4 alkylene group from -(C1-4 alkylene)a-Q-(C1-4 alkylene)b-group is optionally substituted with 1, 2 or 3 substitutes independently selected from C1-3 alkyl; Q is -O-, -NRq1-, C(=O) or -C(=O)NRq1-, where each Rq1 is independently selected from H and C1-6 alkyl; Cy is a group of formulas (given in the claim), each of which is optionally substituted with 1, 2, 3 or 4 substituents independently selected from RCy; each RCy is independently selected from halogen, C1-6 alkyl, C1-4 haloalkyl, C1-4 cyanoalkyl, CN, ORa1, C(O)NRc1Rd1, C(O)ORa1, NRc1S(O)2Rb1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1 and S(O)2Rb1, where said radicals are optionally substituted with 1 or 2 substituents independently selected from ORa1, OC(O)Rb1 and C(O)ORa1; R1 is H, ORa2, NRc2Rd2 or C1-6 alkyl; Z is ORa3 or C(O)NRc3Rd3; each R2, R3, R4 and R5 independently represents H; each Ra1, Rb1, Rc1, Rd1, Ra2, Rc2, Rd2, Ra3, Rc3 and Rd3 is independently selected from H, C1-6 alkyl and C3-10 cycloalkyl-C1-6 alkyl, where said C1-6 alkyl and C3-10 cycloalkyl-C1-6 alkyl, each optionally substituted with 1, 2, 3, 4 or 5 substitutes independently selected from Rg; each Rg is OH; n is 0 or 1; m is 0 or 1; p is 0, 1, 2 or 3; r is 0, 1 or 2; a has value of 0 or 1; and b is 0 or 1, where any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups. Invention also relates to specific compounds. Invention relates to a pharmaceutical composition which inhibits the interaction between menin and MLL, comprising a therapeutically effective amount of a compound according to the invention or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. Compounds according to the invention are intended for use in preparing a drug for inhibiting the interaction between menin and MLL.;EFFECT: inhibitors of interaction of menin with MLL and MLL fusion proteins.;47 cl, 16 tbl, 1 dwg, 142 ex;