Bifunctional selective degraders of smarca2 and therapeutic uses thereof

A compound having a structure represented by Formula (II):

• or a stereoisomer, pharmaceutically acceptable salt thereof, wherein:
• t and q is independently 0 or 1;
• Z is —N— or —C(R3)—;
• R1 is hydrogen or C1-6 alkyl optionally substituted with 1 to 3 Ra;
• R2 is hydrogen, halo, hydroxyl, —O—Rc, C1-6 alkyl optionally substituted with 1 to 3 Ra;
• R3 is hydrogen, —CN, halo (preferably F), —O—Re, C1-6 alkyl, C6-12 aryl, C3-12 cycloalkyl, 5-12 membered heteroaryl, wherein each of C1-6 alkyl, C6-12 aryl, C3-12 cycloalkyl, and 5-12 membered heteroaryl is optionally substituted with 1 to 3 Rd;
• R4a and R4b are each independently hydrogen, C1-6 alkyl or C1-6 alkoxy, or
• R4a and R4b together may form a C1-3 alkylene chain;
• or
• R4a and R3 together with the carbons to which they are attached form a C3-12 cycloalkyl or 5-12 membered heterocycle,
• L comprises up to 8 linker segments represented by -L1-L2-L3-L4-L5-L6-L7-L8-, each L1, L2, L3, L4, L5, L6, L7, or L8, being independently:
• i) C3-12 cycloalkyl optionally substituted with 1-3 Rb;
• ii) C6-12 aryl optionally substituted with 1-3 Rb;
• iii) 4-12 membered heterocyclyl optionally substituted with 1-3 Rb;
• iv) 5-12 membered heteroaryl optionally substituted with 1-3 Rb;
• v) direct bond;
• vi) C1-12 alkylene chain optionally substituted with 1-3 Rb;
• vii) C1-12 alkenylene chain optionally substituted with 1-3 Rb;
• or
• viii) —(CH2)m—C(O)—, —(CH2)m—C(O)O—, —(CH2)m—O—, —(CH2)m—N(Rc)—, —(CH2)m—S—, —(CH2)m—C(S)—, —(CH2)m—C(S)—O—, —(CH2)m—S(O)2—, —(CH2)m—S(O)═N—, —(CH2)m—S(O)2NH—, —(CH2)m—C(O)—N(Rc)—, —C(O)—N(Rc)—(CH2)m—, —(CH2)m—O—C(O)—N(Rc)—, —(CH2)m—O—C(O)—O—, or —NH—(CH2)m—C(O)—, wherein m is 0, 1, 2, 3, 4, 5 or 6;
• each Ra is independently halo, or —O—Rc;
• each Rb is independently oxo, imino, sulfoximino, halo, nitro, —CN, C1-6 alkyl, C2-6 alkenyl, C3-15 cycloalkyl, C1-8 haloalkyl, C6-12 aryl, 5-12 membered heteroaryl, 4-12 membered heterocyclyl, —O—Rc, —C(O)—Rc, —C(O)O—Rc, —C(O)—N(Rc)(Rc), —N(Rc)(Rc), —N(Rc)C(O)—Rc, —N(Rc)C(O)O—Rc, —N(Rc)C(O)N(Rc)(Rc), —N(Rc)S(O)2(Rc), —NRcS(O)2N(Rc)(Rc), —N(Rc)S(O)2O(Rc), —OC(O)Rc, —OC(O)—N(Rc)(Rc), —Si(Rc)3, —S—Rc, —S(O)Rc, —S(O)(NH)Rc, —S(O)2Rc or —S(O)2N(Rc)(Rc), wherein each of C1-6 alkyl, C2-6 alkenyl, C3-15 cycloalkyl, C1-8 haloalkyl, C6-12 aryl, 5-12 membered heteroaryl, and 4-12 membered heterocyclyl may be optionally substituted with 1 to 3 Rd;
• each Rc is independently hydrogen, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl (optionally substituted with 1 or 2 halo, C1-3 alkyl or C1-3 alkoxy), C6-12 aryl, 4-12 membered heterocyclyl optionally substituted with 1 or 2 C1-3 alkyl), 5-12 membered heteroaryl optionally substituted with 1 or 2 C1-3 alkyl or C1-3 haloalkyl) or C1-6 haloalkyl, wherein C1-6 alkyl is optionally substituted with one or more substituents selected from C1-3 alkoxy, hydroxy, C3-6 cycloalkyl (optionally further substituted with 1 or 2 halo, C1-3 alkoxy or C1-3 alkyl), CN, 5-12 membered heteroaryl (optionally further substituted with 1 or 2 halo or C1-3 alkyl), C6-12 aryl and amino;
• each Rd is independently halo, —CN, —O—Rc, C1-6 alkyl, C6-12 aryl, C3-6 cycloalkyl or C1-6 haloalkyl;
• Re is C1-6 alkyl, C3-12 cycloalkyl, C6-12 aryl, 5-12 membered heteroaryl, each being optionally substituted with C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl or halo;
• W is —C(Rg)— or —N—;
• Y is direct bond, C1-4 alkylene chain, —C(O)—, —C(O)O—, —O—, —N(Rg)—, —S— —C(S)—, —C(S)—O—, —O—C(O)O—, —C(O)—N(Rg)—, or —O—C(O)—N(Rg)—;
• B ring is C6-12 aryl, 5-12 membered heteroaryl, or 4-12 membered heterocyclyl, each being optionally substituted with 1 to 3 Rj;
• Rg is hydrogen or C1-6 alkyl;
• and
• each Rj is independently halo, oxo, —CN, —O—Rc, C1-6 alkyl, or C1-6 haloalkyl.