Compounds and pharmaceutical compositions that degrade swi/snf-related matrix-associated actin-dependent regulator of chromatin subfamily a

A compound of formula IA:

• or a pharmaceutically acceptable salt, solvate, stereoisomer, or tautomer thereof, wherein:
• X is hydroxy, halo, cyano, C1-4 alkoxy, or —N(R)2;
• Y is N, C, or CH;
• Y1 is N, C, or CH;
• T is —N(R)2;
• Ring A is C4-8 cycloalkyl, C6-10 aryl, 4- to 11-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each heterocycloalkyl or heteroaryl have from 1 to 3 heteroatoms selected from O, N, NR, and S, and wherein each cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is independently unsubstituted or substituted with one to four R1;
• L is a bond, —CH2—, or —O—;
• L1 is —RC=CR— or —C≡C—;
• L2 is selected from:
• wherein t is 0 or 1, p is 0, 1, 2, or 3, and wherein the dashed line (), denotes the point of attachment from L2 to L1, and the wavy line () denotes the point of attachment from L2 to Z;
• Z is C1-10 alkyl, —N(R)2, —OH, C1-10 alkoxy, C3-8 cycloalkyl, 4- to 10-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each heterocycloalkyl or heteroaryl have from 1 to 4 heteroatoms selected from NR, N, O, and S, and wherein each heterocycloalkyl or heteroaryl is independently unsubstituted or substituted with one to four R2, and wherein each alkyl, alkoxy, or cycloalkyl is independently unsubstituted or substituted with one to three R3;
• each R is independently hydrogen, C1-4 alkyl, or C3-6 cycloalkyl, wherein each alkyl or cycloalkyl is unsubstituted or substituted with one to three R4;
• or
• two R groups, when attached to the same nitrogen, form a 4- to 7-membered heterocycloalkyl, which is unsubstituted or substituted with one to four R4;
• each Rx and Ry is independently hydrogen, C1-4 alkyl, or C1-4 haloalkyl substituted with 1 to 3 halo;
• or
• Rx and Ry, together with the atoms to which they are attached, form a C3-6 cycloalkyl, which is unsubstituted or substituted with one to four R4;
• each R1 is independently cyano, halo, hydroxyl, nitro, oxo, —N(R)2, C1-4 alkyl, C1-4 haloalkyl substituted with 1 to 3 halo, C1-4 alkoxy unsubstituted or substituted with 1 to 3 halo, C5-6 heteroaryl having from 1 to 3 heteroatoms selected from O, N, NR, and/or S, 4- to 7-membered heterocycloalkyl having from 1 to 3 heteroatoms selected from oxygen, nitrogen, and/or sulfur, —C(O)OR, —OC(O)R, or —C(O)R;
• each R2 is independently oxo, hydroxy, cyano, halo, —N(R)2, —C(O)OR, —NRC(O)OR, C1-4 alkyl, C1-4 haloalkyl substituted with from 1 to 3 halo groups, C1-4 alkoxy, C1-4 alkoxy substituted with from 1 to 3 halo groups, C1-4 alkyl substituted with C1-2 alkoxy, C5-6 heteroaryl having from 1 to 3 heteroatoms selected from O, N, and NR, or C3-6 cycloalkyl;
• each R3 is independently oxo, cyano, hydroxy, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxy substituted with from 1 to 3 halo groups, C1-4 haloalkyl substituted with from 1 to 3 halo groups, C1-6 aryl, C1-4 alkyl substituted with 1 to 3 phenyl, or C3-6 cycloalkyl;
• each R4 is independently —N(R)2, cyano, halo, or hydroxyl;
• each R5 is D, halo, C1-3 haloalkyl, or C1-4 alkoxy;
• each R6 is N(R)2, SR, halo, cyano, C1-4 alkoxy unsubstituted or substituted with 1 to 3 halo, unsubstituted C1-4 alkyl, C1-4 alkyl substituted with C1-2 alkoxy, or C1-4 alkyl substituted with hydroxy;
• m is 0, 1, or 2;
• and
• n is 0, 1, 2, or 3;
• with the proviso that the compound is not 2-[6-amino-5-[8-[2-[3-(azepan-1-yl)prop-1-ynyl]pyrimidin-4-yl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol.

A compound of formula I′:

• or a pharmaceutically acceptable salt, solvate, stereoisomer, or tautomer thereof, wherein:
• X is hydroxy, halo, cyano, C1-4 alkoxy, or —N(R)2;
• Y is N, C, or CH;
• Y1 is N, C, or CH;
• T is —N(R)2;
• Ring A is C4-8 cycloalkyl, C6-10 aryl, 4- to 11-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each heterocycloalkyl or heteroaryl have from 1 to 3 heteroatoms selected from O, N, NR, and S, and wherein each cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is independently unsubstituted or substituted with one to four R1;
• L1 is —RC=CR— or —C≡C—;
• L2 is selected from:
• wherein t is 0 or 1, p is 0, 1, 2, or 3, and wherein the dashed line () denotes the point of attachment from L2 to L1, and the wavy line () denotes the point of attachment from L2 to Z;
• Z is C1-10 alkyl, —N(R)2, —OH, C1-10 alkoxy, C3-8 cycloalkyl, 4- to 10-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each heterocycloalkyl or heteroaryl have from 1 to 4 heteroatoms selected from NR, N, O, and S, and wherein each heterocycloalkyl or heteroaryl is independently unsubstituted or substituted with one to four R2, and wherein each alkyl, alkoxy, or cycloalkyl is independently unsubstituted or substituted with one to three R3;
• each R is independently hydrogen, C1-4 alkyl, or C3-6 cycloalkyl, wherein each alkyl or cycloalkyl is unsubstituted or substituted with one to three R4;
• or
• two R groups, when attached to the same nitrogen, form a 4- to 7-membered heterocycloalkyl, which is unsubstituted or substituted with one to four R4;
• each Rx and Ry is independently hydrogen, C1-4 alkyl, or C1-4 haloalkyl substituted with 1 to 3 halo;
• or
• Rx and Ry, together with the atoms to which they are attached, form a C3-6 cycloalkyl, which is unsubstituted or substituted with one to four R4;
• each R1 is independently cyano, halo, hydroxyl, nitro, oxo, —N(R)2, C1-4 alkyl, C1-4 haloalkyl substituted with 1 to 3 halo, C1-4 alkoxy unsubstituted or substituted with 1 to 3 halo, C5-6 heteroaryl having from 1 to 3 heteroatoms selected from O, N, NR, and/or S, 4- to 7-membered heterocycloalkyl having from 1 to 3 heteroatoms selected from oxygen, nitrogen, and/or sulfur, —C(O)OR, —OC(O)R, or —C(O)R;
• each R2 is independently oxo, hydroxy, cyano, halo, —N(R)2, —C(O)OR, —NRC(O)OR, C1-4 alkyl, C1-4 haloalkyl substituted with from 1 to 3 halo groups, C1-4 alkoxy, C1-4 alkoxy substituted with from 1 to 3 halo groups, C1-4 alkyl substituted with C1-2 alkoxy, C5-6 heteroaryl having from 1 to 3 heteroatoms selected from O, N, and NR, or C3-6 cycloalkyl;
• each R3 is independently oxo, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxy substituted with from 1 to 3 halo groups, C1-4 haloalkyl substituted with from 1 to 3 halo groups, or C3-6 cycloalkyl;
• each R4 is independently —N(R)2, cyano, halo, or hydroxyl;
• each R5 is D, halo, C1-3 haloalkyl, or C1-4 alkoxy;
• each R6 is N(R)2, SR, cyano, C1-4 alkoxy unsubstituted or substituted with 1 to 3 halo, C1-4 alkyl substituted with C1-2 alkoxy, or C1-4 alkyl substituted with hydroxy;
• m is 0, 1, or 2;
• and
• n is 0, 1, 2, or 3;
• with the proviso that the compound is not 2-[6-amino-5-[8-[2-[3-(azepan-1-yl)prop-1-ynyl]pyrimidin-4-yl]-3,8-diazabicyclo[3.2.1]octan-3-yl]pyridazin-3-yl]phenol.