Dot1l degraders and uses thereof

A compound of Formula (I):

• or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein:
• R8 is hydrogen, optionally substituted acyl, optionally substituted alkyl, or a nitrogen protecting group;
• R9 is hydrogen, optionally substituted acyl, optionally substituted alkyl, or a nitrogen protecting group;
• R10 is hydrogen, optionally substituted acyl, optionally substituted alkyl, or a nitrogen protecting group;
• R11 is halogen, optionally substituted acyl, or optionally substituted alkyl;
• each instance of R12 is independently hydrogen, optionally substituted acyl, or an oxygen protecting group;
• L is
• and
• lR indicates the point of attachment to D, and lA indicates the point of attachment to the moiety of formula
• X is —CH2— or —O—;
• ring B is an optionally substituted 5-10 membered heterocyclyl or optionally substituted 5-14 membered heteroaryl group;
• n1 is 1, 2, 3, 4, 5, or 6;
• n2 is 1, 2, 3, 4, 5, or 6;
• n3 is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12;
• g is 1, 2, 3, 4, 5, or 6;
• and
• g1 is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
• and
• D is of the formula IA or IB:
• wherein:
• for each set of two moieties A bound to the same carbon atom, one A is hydrogen, and the other A is one of:
• (i) phenyl, optionally substituted with 1-5 substituents selected from the group consisting of —R1, —OR1, —NR1R2, —S(O)qR1, —SO2R1R2, —NR1SO2R2, —C(O)R1, —C(O)OR1, —C(O)NR1R2, —NRIC(O)R2, —NRIC(O)OR2, —CHF2, —CH2F, —CF3, and —OCF3;
• (ii) naphthyl, optionally substituted with 1-5 substituents selected from the group consisting of —R1, —OR1, —NR1R2, —S(O)qR1, —SO2R1R2, —NR1SO2R2, —C(O)R1, —C(O)OR1, —C(O)NR1R2, —NRIC(O)R2, —NRIC(O)OR2, —CHF2, —CH2F, —CF3, and —OCF3;
• (iii) a 5- or 6-membered monocyclic heteroaryl group, having 1-3 heteroatoms selected from the group consisting of O, N, and S, optionally substituted with 1-3 substituents selected from the group consisting of —R1, —OR1, —NR1R2, —S(O)qR1, —SO2R1R2, —NR1SO2R2, —C(O)R1, —C(O)OR1, —C(O)NR1R2, —NR1C(O)R2, —NRIC(O)OR2, —CHF2, —CH2F, —CF3, and —OCF3;
• and
• (iv) an 8- to 10-membered bicyclic heteroaryl group containing 1-3 heteroatoms selected from the group consisting of O, N, and S, and having a first ring fused to a second ring through 3 to 4 carbon atoms, wherein the bicyclic heteroaryl group is optionally substituted with 1-3 substituents selected from the group consisting
• of —R1, —OR1, —NR1R2, —S(O)qR1, —SO2R1R2, —NR1SO2R2, —C(O)R1, —C(O)OR1, —C(O)NR1R2, —NR1C(O)R2, —NR1C(O)OR2, —CHF2, —CH2F, —CF3, and —OCF3;
• Y is ═O, ═S, ═NR1, or ═CR1R2,
• R1 and R2 are each independently selected from the group consisting of hydrogen, nitro, hydroxyl, —COOH, —NH2, halogen, cyano, and C1-C14 alkyl optionally substituted with 1-3 substituents selected from the group consisting of C1-C14 alkyl, C1-C14haloalkyl, C1—C14 alkoxy, nitro, hydroxyl, —COOH, —NH2, C1-C14 alkylamino, C1-C14 dialkylamino, halogen, and cyano;
• R7 is hydrogen, optionally substituted C1-6 alkyl, or a nitrogen protecting group;
• Z is selected from the group consisting of hydrogen, optionally substituted C1-C14 alkyl, optionally substituted C3-C10 cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted alkyl-aryl, and —(CH2)p—K;
• K is a 5- or 6-membered monocyclic heterocyclic or heteroaryl group containing 1-4 heteroatoms selected from the group consisting of O, N, and S, or an 8- to 10-membered bicyclic heteroaryl group containing 1-4 heteroatoms selected from the group consisting of 0, N, and S;
• p is an integer selected from the group consisting of 0, 1, 2, 3, and 4;
• and
• q is an integer selected from the group consisting of 0, 1, and 2.