Menin-mll inhibitors and methods of use thereof

A composition comprising a compound having the structure of formula I:

• wherein Y is independently selected from OH, OR7, NH2, NHR7, or NR7aR7b;
• wherein R7 selected from C1-6-alkyl, monohalo-C1-6-alkyl, polyhalo-C1-6-alkyl, (C1-4-alkyloxy)-C1-6-alkyl, (C1-4-dialkylamino)-C1-6-alkyl, C1-4—(C3-6-cycloalkyl), C1-4—(C5-6-heteroaryl), C1-4—(C5-6-aryl), C1-4—OH, C1-4—NH2, and C1-4—CN;
• wherein R7a and R7b are selected from C1-6-alkyl, monohalo-C1-6-alkyl, polyhalo-C1-6-alkyl, (C1-4-alkyloxy)-C1-6-alkyl, (C1-4-dialkylamino)-C1-6-alkyl, C1-4—(C3-6-cycloalkyl), C1-4—(C5-6-heteroaryl), C1-4—(C5-6-aryl), C1-4—OH, C1-4—NH2, and C1-4—CN, or may form a ring between R7a and R7b with C3-7 carbons;
• wherein R1 is aryl or heteroaryl and substituted with 0, 1, 2, or 3 groups each independently selected from cyano, halo, hydroxyl, C1-3-alkyl, C1-3-alkyloxy, monohalo-C1-3-alkyl, polyhalo-C1-3-alkyl, and sulfonyl-C1-3-alkyl;
• wherein R2 is selected from heteroaryl, heterocycle, carbocycle containing a C3-8 ring size, or acyclic C1-6-alkyl;
• wherein R2 is substituted with 0, 1, 2, or 3 groups each independently selected from cyano, halo, hydroxyl, C1-3-alkyl, C1-3-alkyloxy, monohalo-C1-3-alkyl, polyhalo-C1-3-alkyl, and sulfonyl-C1-3-alkyl;
• wherein A is a 1,4-disubstituted aryl or heteroaryl ring substituted with X and R3 and may contain a third group R6 independently selected from cyano, halo, hydroxyl, C1-3-alkyl, C1-3 alkyloxy, monohalo-C1-3-alkyl, polyhalo-C1-3-alkyl, sulfonyl-C1-3-alkyl and sulfonamide;
• wherein X is O, NH, or NR8;
• wherein when X is NR8, R8 may be independently selected from C1-3-alkyl, C1-3-alkyloxy, monohalo-C1-3-alkyl, polyhalo-C1-3-alkyl, and sulfonyl-C1-3-alkyl
• wherein R3 is CN, SO2NH2, SO2NR9aR9b, CONR9aR9b, SO2CH3, OCF3, CF3, Cl, CH3, CH2CN, CH2NH2, CH2NHC(O)R10, CH2NHSO2R10, NO2, 4-pyridyl, 3-pyridyl, C(O)R, 1,2,3-triazole, OCH3;
• wherein R9a and R9b may be independently selected from hydrogen, C1-3-alkyl, or polyhalo-C1-3-alkyl, or may form a ring between R9a and R9b with C3-7 carbons;
• wherein R10 is C1-3-alkyl;
• or polyhalo-C1-3-alkyl;
• wherein R4 is hydrogen, or C1-3-alkyl;
• and
• wherein R5 is hydrogen, OH, or C1-3-alkyl.