Herboxidiene antibody-drug conjugates and methods of use
AssigneeEisai R&D Management Co., Ltd.
InventorsNathan Fishkin, Thiwanka Samarakoon, James Palacino, Kenzo Arai, Yoshihiko Kotake, Shinya Okubo, Norio Murai, Masayuki Miyano
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Abstract
Linker-drug compounds and antibody-drug conjugates that bind to human oncology targets are disclosed. The linker-drug compounds and antibody-drug conjugates comprise a herboxidiene splicing modulator drug moiety. The disclosure further relates to methods and compositions for use in the treatment of neoplastic disorders by administering the antibody-drug conjugates provided herein.
Claims31
1-751. (canceled)
A splicing modulator which is a compound of the following formula:
- a pharmaceutically acceptable salt thereof, wherein:
- X is NR6R7;
- R6 and R7 are each independently chosen from hydrogen, —R8, —C(═O)—R8, —C(═O)—O—R3, —(C1-C6 alkyl)-O—C(═O)—R8, and —(C1-C6 alkyl)-NH—C(═O)—R8;
- and
- R8 is chosen from C1-C6 alkyl groups, C3-C8 carbocyclyl groups, and C3-C8 heterocyclyl groups,
- wherein R6, R7, and R8 are each independently substituted with 0 to 3 groups independently chosen from halogens, hydroxyl, C1-C6 alkyl groups, —O—(C1-C6 alkyl) groups, —CO2H, —C(═O)—O—(C1-C6 alkyl) groups, —C(═O)—(C1-C6 alkyl) groups, —C(═O)—(C3-C8 carbocyclyl) groups, —C(═O)—(C3-C8 heterocyclyl) groups, —NR6R7, C3-C8 carbocyclyl groups, C1-C6 alkylhydroxy groups, C1-C6 alkylalkoxy groups, benzyl groups, and C3-C8 heterocyclyl groups, each of which may be independently substituted with 0 or 1 group chosen from halogens, hydroxyl, C1-C3 alkyl groups, C1-C3 alkoxy groups, C1-C3 haloalkyl groups, —NH—C(═O)(C1-C3 alkyl), and —NH—C(═O)—O—(C1-C3 alkyl).
A splicing modulator which is a compound of the following formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- R1, R2, and R3 are each independently chosen from hydrogen, hydroxyl, —O—(C1-C6 alkyl) groups, —O—C(═O)—(C1-C6 alkyl) groups, —C(═O)—O—(C1-C6 alkyl) groups, and C1-C6 alkyl groups;
- R6 and R7 are each independently chosen from hydrogen, —R8, —C(═O)—R8, and —C(═O)—O—R8;
- R8 is chosen from C1-C6 alkyl groups, C3-C8 carbocyclyl groups, and C3-C8 heterocyclyl groups;
- and
- R9 is chosen from H,
- wherein R1, R2, R3, R6, R7, and R8 are each independently substituted with 0 to 3 groups independently chosen from halogens, hydroxyl, C1-C6 alkyl groups, —O—(C1-C6 alkyl) groups, —CO2H, —C(═O)—(C1-C6 alkyl) groups, —C(═O)—(C3-C3 carbocyclyl) groups, —C(═O)—(C3-C3 heterocyclyl) groups, —NR6R7, C3-C3 carbocyclyl groups, C1-C6 alkylhydroxy groups, C1-C6 alkylalkoxy groups, benzyl groups, and C3-C8 heterocyclyl groups, each of which may be independently substituted with 0 or 1 group chosen from halogens, hydroxyl, C1-C3 alkyl groups, C1-C3 alkoxy groups, C1-C3 haloalkyl groups, —NH—C(═O)(C1-C3 alkyl), and —NH—C(═O)—O—(C1-C3 alkyl);
- and
- wherein * denotes the point of connectivity of R9 to the remainder of the compound.
Dependencies are inferred from the claim text.