# US 2019/0169215 A1 · Aryl imidazoles for treatment of cancer

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2019/0169215 A1
- Document ID: US20190169215A1
- Status: Published application
- Kind: A1
- Application number: 16/174,938
- Filed: 2018-10-30
- Published: 2019-06-06
- Earliest claimed: 2017-10-30
- Assignees: Aptose Biosciences Inc.
- Applicants: Aptose Biosciences Inc.
- Inventors: William G. RICE; Stephen H. HOWELL; Cheng-Yu TSAI
- Web page: https://patentgrep.com/patent/US20190169215A1

## CPC

- C07F 15/025: {without a metal-carbon linkage}
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- C07D 471/14: Ortho-condensed systems
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to a method of preventing, reducing, or treating cancer in a subject, comprising administering a therapeutically effective amount of or a pharmaceutically acceptable salt, free base, hydrate, complex, or chelate (including metal chelates, such as iron, zinc and others) thereof to the subject, wherein the subject has a mutation in a DNA repair gene.

## Claims

### Claim 1

A method of preventing, reducing or treating cancer in a subject, comprising administering a therapeutically effective amount of Compound I:
or a pharmaceutically acceptable salt, free base, hydrate, complex, or chelate thereof to the subject; wherein the subject has a mutation in a DNA repair gene.

### Claim 2 (depends on 1)

The method of claim 1, wherein the DNA repair gene is a homologous recombinant gene.

### Claim 3 (depends on 1)

The method of claim 1, wherein the DNA repair gene is a gene in the homologous recombination (HR) dependent deoxyribonucleic acid (DNA) double strand break (DSB) repair pathway.

### Claim 4 (depends on 1)

The method of claim 1, wherein the DNA repair gene is one or more genes selected from the group consisting of BRCA-1, BRCA-2, ATM, ATR, CHK1, CHK2, Rad51, RPA and XRCC3.

### Claim 5 (depends on 2)

The method of claim 2, wherein the DNA repair gene is BRCA-1 and/or BRCA-2.

### Claim 6 (depends on 1)

The method of claim 1, wherein the subject is heterozygous for a mutation in a DNA repair gene.

### Claim 7 (depends on 6)

The method of claim 6, wherein the subject is heterozygous for a mutation in a gene in the homologous recombination (HR) dependent deoxyribonucleic acid (DNA) double strand break (DSB) repair pathway.

### Claim 8 (depends on 6)

The method of claim 6, wherein the subject is heterozygous for a mutation in BRCA1 or BRCA2.

### Claim 9 (depends on 6)

The method of claim 6, wherein the subject is homozygous for a mutation in BRCA1 or BRCA2.

### Claim 10 (depends on 1)

The method of claim 1, wherein the cancer is selected from the group consisting of heme cancer, colorectal cancer, ovarian cancer, breast cancer, cervical cancer, lung cancer, liver cancer, pancreatic cancer, cancer of the lymph nodes, leukemia, renal cancer, colon cancer, prostate cancer, brain cancer, cancer of the head and neck, bone cancer, carcinoma of the larynx and oral cavity, Ewing's sarcoma, skin cancer, kidney cancer, and cancer of the heart.

### Claim 11 (depends on 10)

The method of claim 10, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, cancer of the lymph nodes, colon cancer, leukemia, renal cancer, and prostate cancer.

### Claim 12 (depends on 11)

The method of claim 11, wherein the cancer is breast cancer.

### Claim 13 (depends on 1)

The method of claim 1, wherein the cancer is a BRCA-associated cancer.

### Claim 14 (depends on 13)

The method of claim 13, wherein the BRCA-associated cancer has one or more mutations of the BRCA-1 and/or BRCA-2 genes.

### Claim 15 (depends on 1)

The method of claim 1, wherein the subject is human.

### Claim 16 (depends on 1)

The method of claim 1, further comprising the administering of a therapeutically effective amount of a second therapeutically active agent.

### Claim 17 (depends on 16)

The method of claim 16, wherein the second therapeutically active agent is administered before, during, or after the subject has been administered Compound I.

### Claim 18 (depends on 16)

The method of claim 16, wherein the second therapeutically active agent is selected from one or more of the group consisting of immunotherapeutic agents, anticancer agents, and angiogenic agents.

### Claim 19 (depends on 18)

The method of claim 18, wherein the second therapeutically active agent is a PARP inhibitor.

### Claim 20 (depends on 19)

The method of claim 19, wherein the PARP inhibitor is olaparib.

### Claim 21 (depends on 1)

The method of claim 1, wherein the subject experiences less than a 90% decrease in bone marrow activity relative to a subject who was not administered a therapeutically effective amount of Compound I
or a pharmaceutically acceptable salt, free base, hydrate, complex, or chelate thereof.

### Claim 22 (depends on 21)

The method of claim 21, wherein the subject experiences less than a 10% decrease in bone marrow activity.

### Claim 23 (depends on 21)

The method of claim 21, wherein the subject experiences no decrease in bone marrow activity.

### Claim 24 (depends on 1)

The method of claim 1, wherein the subject already has cancer.

### Claim 25 (depends on 24)

The method of claim 24, wherein the subject experiences a reduction or decrease in size of a tumor associated with a cancer.

### Claim 26 (depends on 25)

The method of claim 25, wherein the subject experiences complete elimination of the tumor associated with cancer.

### Claim 27 (depends on 24)

The method of claim 24, wherein the subject experiences an inhibition, decrease, or reduction of neo-vascularization or angiogenesis in a tumor associated with a cancer.

### Claim 28

A method for killing cancer cells, comprising contacting said cells with a therapeutically effective amount of Compound I
or a pharmaceutically acceptable salt, free base, hydrate, complex, or chelate thereof.

### Claim 29 (depends on 28)

The method of claim 28, wherein the cancer cells have a deficiency in one or more genes selected from the group consisting of BRCA-1, BRCA-2, ATM, ATR, CHK1, CHK2, Rad51, RPA and XRCC3.

### Claim 30

A method for inducing cell cycle arrest in cancer cells, comprising contacting said cells with a therapeutically effective amount of Compound I
or a pharmaceutically acceptable salt, free base, hydrate, complex, or chelate thereof.

### Claim 31 (depends on 30)

The method of claim 30, wherein the cancer cells have a deficiency in one or more genes selected from the group consisting of BRCA-1, BRCA-2, ATM, ATR, CHK1, CHK2, Rad51, RPA and XRCC3.

### Claim 32

A method of preventing, reducing or treating cancer in a subject, comprising administering a therapeutically effective amount of one or more molecules of
in complex with one or more metal atoms, wherein the subject has a mutation in a DNA repair gene.

### Claim 33 (depends on 32)

The method of claim 32, wherein the one or more metal atoms are selected from the group consisting of iron, zinc, aluminum, magnesium, platinum, silver, gold, chromium, nickel, titanium, copper, scandium, zirconium, vanadium, molybdenum, manganese, tungsten and cobalt.

### Claim 34 (depends on 33)

The method of claim 33, wherein the one or more metal atoms are iron.

### Claim 35 (depends on 34)

The method of claim 34, wherein the complex has the following structure: