Irreversible inhibitors of menin-mll interaction

Disclosed herein are heterocyclic compounds of formula (I) that inhibit the binding of menin and MLL or MLL fusion proteins; and wherein: A is N; Cy is a bicyclic heteroaryl group which is further substituted with a 4- to 7-membered heterocycloalkyl ring, phenyl, an 8- to -10-membered bicyclic aryl ring, or 5- or 6-membered heteroaryl ring; X is -C(R3b)2-, -NR3a-, or -O-; W is -C(O)-, -S(O)-, or -S(O)2-; Y is a single bond, -C(R3b)2-, -NR3a-, or -O-; one of R1 or R2 is selected from the group CH2-Cy2-NHC(O)-C(R6a)=C(R6b)(R6c) or Cy2-NHC(O)-C(R6a)=C(R6b)(R6c); and where in the remaining substituents are as defined herein. Representative compounds of formula (I) include compounds such as N-[4-[4-(morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-4-[[3(R)-[(1-oxo-2-propen-1-yl)amino]-piperidin-1-yl]methyl]-pyridine-2-carboxamide. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the menin-MLL irreversible inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, leukemia and other diseases or conditions dependent on menin-MLL interaction.