Benzazepine compounds, conjugates, and uses thereof

A method of treating breast cancer, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising a conjugate having the following formula:

• wherein Antibody is an antibody construct, L3 is a linker, and D is a compound represented by the structure of Formula (IIIA):
• or a pharmaceutically acceptable salt thereof, wherein:
• represents an optional double bond;
• L11 is selected from —C(O)— and —C(O)N(R10)—*, wherein * represents where L11 is bound to R6;
• L2 is selected from a bond and —C(O)—;
• R1 and R2 are independently selected from hydrogen, C1-10 alkyl, C2-10 alkenyl and C1-10 alkynyl;
• R4 is selected from:
• —OR10, —N(R10)2, —C(O)N(R10)2, —C(O)R10, —C(O)OR10, —S(O)R10, —S(O)2R10, C1-10 alkyl, C2-10 alkenyl, and C2-10 alkynyl;
• R6 is selected from phenyl and 5- or 6-membered heteroaryl, any one of which is substituted with one or more substituents selected from R7 and R6 is further optionally substituted by one or more additional substituents independently selected from R12;
• R7 is selected from —C(O)NHNH2, —C(O)NH—C1-3alkylene-NH(R10), —C(O)CH3, —C1-3alkylene-NHC(O)OR11, —C1-3alkylene-NHC(O)R10, —C1-3alkylene-NHC(O)NHR10, —C1-3alkylene-NHC(O)—C1-3alkylene-R10, and a 3- to 12-membered heterocycle optionally substituted with one or more substituents independently selected from R12;
• R10 is independently selected at each occurrence from hydrogen, —NH2, and —C(O)OCH2C6H5;
• and C1-10alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OH, —CN, —NO2, —NH2, ═O, ═S, —C(O)OCH2C6H5, —NHC(O)OCH2C6H5, —C1-10 alkyl, —C1-10 haloalkyl, —O—C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle;
• R11 is selected from C3-12 carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from R12;
• and
• R12 is independently selected at each occurrence from halogen, —OR10, —SR10, —N(R10)2, —C(O)R10, —C(O)N(R10)2, —N(R10)C(O)R10, —C(O)OR10, —OC(O)R10, —S(O)R10, —S(O)2R10, —P(O)(OR10)2, —OP(O)(OR10)2, —NO2, ═O, ═S, ═N(R10), and —CN;
• C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10, —SR10, —N(R10)2, —C(O)R10, —C(O)N(R10)2, —N(R10)C(O)R10, —C(O)OR10, —OC(O)R10, —S(O)R10, —S(O)2R10, —P(O)(OR10)2, —OP(O)(OR10)2, —NO2, ═O, ═S, ═N(R10), —CN, C3-10 carbocycle and 3- to 10-membered heterocycle;
• and C3-10 carbocycle and 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from halogen, —OR10, —SR10, —N(R10)2, —C(O)R10, —C(O)N(R10)2, —N(R10)C(O)R10, —C(O)OR10, —OC(O)R10, —S(O)R10, —S(O)2R10, —P(O)(OR10)2, —OP(O)(OR10)2, —NO2, ═O, ═S, ═N(R10), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, and
• wherein the antibody construct specifically binds to human HER2, TROP2 or Liv-1,
• and wherein L3 is bound to a substitutable nitrogen or oxygen of the compound or salt of Formula (IIIA).