Substituted benzothiophene analogs as selective estrogen receptor degraders

A compound having a structure represented by a formula:

• wherein m is selected from 0 and 1;
• wherein n is selected from 1, 2, and 3;
• wherein p is selected from 0, 1, and 2;
• wherein q is selected from 0, 1, and 2;
• wherein each of Z1 and Z2 is independently selected from —CH— or —N—;
• provided Z1 and Z2 are not simultaneously —CH— or —N—;
• and provided when Z1 is —CH— and m is 1, that p and q are not both 0;
• wherein Z10 is selected from —O—, —CH2—, —S—, —NR17—, —CHF—, and —CF2—;
• wherein Z11 is, when present, —CH2CH2—;
• wherein Z20 is selected from —O—, —CH2—, —S—, —NR13—, —CHF—, and —CF2-;
• wherein Z30 is selected from —C(O)—, —CF2—, cyclopropyl, —CH2—, and —CHF—;
• wherein Z40 is —(CH2)n—;
• wherein each of R10a and R10b are independently selected from hydrogen, deuterium, halogen, and C1-C3 methyl;
• wherein each of R12a, R12b, R12c, and R12d is independently selected from hydrogen, hydroxyl, thiol, nitroso, —SF5, —OR15, —SR15, —N(R15)2, —CN, —NO2, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, —O(C1-C6 alkyl), —O(C1-C6 haloalkyl), —B(OH)2, —B(OR15)2, —C(O)OR15, —C(O)R16, —C(S)OR15, —C(S)R16, —OSO2OR15, —OSO2R16, —NHSO2OR15, —NHSO2R16, —N(C1-C6 alkyl)SO2OR15, —N(alkyl)SO2R16, —OP(O)(OR15)2, —OP(O)(R16)2, —P(O)(OR15)3, —P(O)(R16)3, —P(O)OR15, —P(O)R16, —SO2R16, —SO2OR15, C1-C6 alkenyl, C1-C6 alkynyl, aryl, —(C1-C6 alkyl)aryl, aryloxy, heteroaryl, and —(C1-C6 alkyl)heteroaryl;
• wherein three of R14a, R14b, R14c, and R14d are independently selected from hydrogen, hydroxyl, thiol, nitroso, —SF5, —OR15, —SR15, —N(R15)2, —CN, —NO2, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, —O(C1-C6 alkyl), —O(C1-C6 haloalkyl), —B(OH)2, —B(OR15)2, —C(O)OR15, —C(O)R16, —C(S)OR15, —C(S)R16, —OSO2OR15, —OSO2R16, —NHSO2OR15, —NHSO2R16, —N(C1-C6 alkyl)SO2OR15, —N(alkyl)SO2R16, —OP(O)(OR15)2, —OP(O)(R16)2, —P(O)(OR15)3, —P(O)(R16)3, —P(O)OR15, —P(O)R16, —SO2R16, —SO2OR15, C1-C6 alkenyl, C1-C6 alkynyl, aryl, —(C1-C6 alkyl)aryl, aryloxy, heteroaryl, and —(C1-C6 alkyl)heteroaryl;
• and
• wherein one of R14a, R14b, R14c, and R14d is selected from hydrogen, hydroxyl, sulfhydryl, halogen, amino, aminoalkyl, —O(C1-C6 alkyl), —S(C1-C6 alkyl), aryloxy, —OC(O)(C1-C6 alkyl), —OC(S)(C1-C6 alkyl), —OC(O)C6H5, —OC(S)C6H5, —OC(O)aryl, —OC(S)aryl, —OC(O)heteroaryl, —OC(S)heteroaryl, —OC(O)O(C1-C6 alkyl), —OC(S)O(C1-C6 alkyl), —OC(O)OC6H5, OC(S)OC6H5, and —OSO2(C2-C6 alkyl);
• wherein each occurrence of R15 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C3-C8 cycloalkyl, aryl, —(C1-C6 alkyl)aryl, heteroaryl, and —(C1-C6 alkyl)heteroaryl;
• wherein each occurrence of R16 is independently selected from —N(R15)2, —SR15, —OR15;
• wherein each of R17 and R18 is independently selected from hydrogen, —C(O)R15, —C(S)R15, —C(O)R16, —C(S)R16, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C3-C8 cycloalkyl, aryl, and heteroaryl;
• wherein R20 is selected from aryl, heteroaryl, thiophenyl, C3-C8 cycloalkyl, and bicyclic heterocyclyl, and wherein R20 is substituted with 0, 1, 2, 3, or 4 groups independently selected from halogen, —SF5, —CN, —NO2, —OR15, —SR15, —N(R15)2, hydroxyl, thiol, nitroso, C1-C6 alkyl, C1-C6 haloalkyl, —O(C1-C6 alkyl), —O(C1-C6 haloalkyl), —B(OH)2, —B(OR15)2, —C(O)OR15, —C(O)R16, —C(S)OR15, —C(S)R16, —OSO2OR15, —OSO2R16, —NHSO2OR15, —NHSO2R16, —N(alkyl)SO2OR15, —N(alkyl)SO2R16, —OP(O)(OR15)2, —OP(O)(R16)2, —P(O)(OR15)3, —P(O)(R16)3, —P(O)OR15, —P(O)R16, —SO2R16, —SO2OR15, C1-C6 alkenyl, C1-C6 alkynyl, aryl, —(C1-C6 alkyl)aryl, aryloxy, heteroaryl, and —(C1-C6 alkyl)heteroaryl;
• or a pharmaceutically acceptable salt thereof.