# US 2023/0054854 A1 · Combinations

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- Number: US 2023/0054854 A1
- Document ID: US20230054854A1
- Status: Published application
- Kind: A1
- Application number: 17/757,530
- Filed: 2020-12-16
- Published: 2023-02-23
- Earliest claimed: 2019-12-20
- Assignees: Recurium IP Holdings, LLC
- Applicants: Recurium IP Holdings, LLC
- Inventors: Ahmed Abdi Samatar; Jiali Li; Hooman Izadi; Peter Qinhua Huang; Joseph Robert Pinchman; Brant Clayton Boren; Kevin Duane Bunker; Fernando Donate
- Web page: https://patentgrep.com/patent/US20230054854A1

## CPC

- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/635: having a heterocyclic ring, e.g. sulfadiazine
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61P 35/00: Antineoplastic agents
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed herein are combinations of compounds for treating a disease or condition, such as cancer. A combination of compounds for treating a disease or condition can include a Bcl-2 inhibitor and a WEE1 inhibitor, along with pharmaceutically acceptable salts of any of the foregoing.

## Claims

### Claim 1

Use of a combination of compounds for treating a disease or condition, wherein the combination includes an effective amount of Compound (A) and an effective amount of one or more of Compound (B), or a pharmaceutically acceptable salt thereof, wherein:
the Compound (A) has the structure:
wherein:
R1 is selected from the group consisting of hydrogen, halogen and a substituted or unsubstituted C1-C6 alkyl;
Ring A is selected from the group consisting of a substituted or unsubstituted phenyl and a substituted or unsubstituted 5-6 membered monocyclic heteroaryl;
Ring B is selected from the group consisting of a substituted or unsubstituted monocyclic 5-7 membered carbocyclyl and a substituted or unsubstituted 5-7 membered monocyclic heterocyclyl;
R2 is selected from the group consisting of
m is 0, 1, 2 or 3;
R3 is selected from the group consisting of halogen and a substituted or unsubstituted C1-C6 alkyl;
X is selected from the group consisting of hydrogen, halogen, hydroxy, cyano, a substituted or unsubstituted 4-6 membered monocyclic heterocyclyl, a substituted or unsubstituted amine(C1-C6 alkyl), a substituted or unsubstituted —NH—(CH2)1-6-amine, a mono-substituted amine, a di-substituted amine, an amino, a substituted or unsubstituted C1-C6 alkyl, a substituted or unsubstituted C1-C6 alkoxy, a substituted or unsubstituted C3-C6 cycloalkoxy, a substituted or unsubstituted (C1-C6 alkyl)acyl, a substituted or unsubstituted C-amido, a substituted or unsubstituted N-amido, a substituted or unsubstituted C-carboxy, a substituted or unsubstituted O-carboxy, a substituted or unsubstituted O-carbamyl and a substituted or unsubstituted N-carbamyl;
Y is CH or N;
Y1 is CR4A or N;
Y2 is CR4B or N;
Ring C is selected from the group consisting of a substituted or unsubstituted C6-C10 aryl, a substituted or unsubstituted monocyclic 5-10 membered heteroaryl, a substituted or unsubstituted monocyclic 5-7 membered carbocyclyl, a substituted or unsubstituted 5-7 membered monocyclic heterocyclyl and a substituted or unsubstituted 7-10 membered bicyclic heterocyclyl;
R4A and R4B are independently selected from the group consisting of hydrogen, halogen and an unsubstituted C1-4 alkyl; and
R5 is a substituted or unsubstituted 5-7 membered monocyclic heterocyclyl; and
the one or more of Compound (B) is a Bcl-2 inhibitor, or a pharmaceutically acceptable salt thereof;
wherein the Bcl-2 inhibitor is selected from the group consisting of AGP-2575, AGP-1252, venetoclax
navitoclax
S55746/BCL201, S65487, BGB-11417, FCN-338 and AZD0466, or a pharmaceutically acceptable salts of any of the foregoing.

### Claim 2 (depends on 1)

The use of claim 1, wherein the Compound (A) is selected from the group consisting of:
or a pharmaceutically acceptable salt of any of the foregoing.

### Claim 3 (depends on 1, 2)

The use of claim 1 or 2, wherein the Compound (A) is selected from the group consisting of:
or a pharmaceutically acceptable salt of any of any of the foregoing.

### Claim 4 (depends on 1, 2, 3)

The use of any one of claims 1-3, wherein the hematological malignancy is acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML).

### Claim 5 (depends on 4)

The use of claim 4, wherein the hematological malignancy is non-Hodgkin's lymphoma.

### Claim 6 (depends on 4)

The use of claim 4, wherein the hematological malignancy is Multiple Myeloma and blastic plasmacytoid dendritic cell neoplasm.

### Claim 7 (depends on 1, 2, 3)

The use of any one of claims 1-3, wherein the disease or condition is a solid tumor.

### Claim 8 (depends on 7)

The use of claim 7, wherein the disease or condition is selected from the group consisting of a bladder cancer, a brain cancer, a breast cancer, a cervical cancer, a choriocarcinoma, a cervicocerebral cancer, a colon cancer, an endometrial cancer, an esophageal cancer, a gallbladder/bile duct cancer, a head and neck cancer (including oral cancer), a hepatocellular cancer, a lung cancer, a non-small cell cancer, a mesothelioma, an ovarian cancer, an osteosarcoma, a pancreatic cancer, a penis cancer, an anal cancer, a prostate cancer, a testicular cancer, a small cell cancer, a small cell lung cancer, a stomach cancer, a rectal cancer, a renal pelvis/ureter cancer, a skin cancer, a soft tissue sarcoma, a stomach cancer, a testicular cancer, a thyroid cancer, an uterus body cancer, and an uterocervical cancer.

### Claim 9 (depends on 8)

The use of claim 8, wherein the disease or condition is breast cancer.

### Claim 10 (depends on 8)

The use of claim 8, wherein the disease or condition is small cell lung cancer.

### Claim 11 (depends on 8)

The use of claim 8, wherein the disease or condition is pancreatic cancer.