# US 2019/0169134 A1 · Novel class of quinolone heterocyclic aromatic molecules for cancer treatment

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- Number: US 2019/0169134 A1
- Document ID: US20190169134A1
- Status: Published application
- Kind: A1
- Application number: 16/272,576
- Filed: 2019-02-11
- Published: 2019-06-06
- Earliest claimed: 2016-11-09
- Assignees: RenoTarget Therapeutics, Inc.
- Applicants: RenoTarget Therapeutics, Inc.
- Inventors: Jujun Wang; Allen Tsao
- Web page: https://patentgrep.com/patent/US20190169134A1

## CPC

- C07D 239/94: Nitrogen atoms
- A61K 31/282: Platinum compounds
- A61K 31/337: having four-membered rings, e.g. taxol
- 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
- A61P 35/00: Antineoplastic agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

The invention is directed to new class of quinolone heterocyclic aromatic molecules (Renotinibs) and their use in the treatment of cancer, in particular, cancer that harbor abnormal human epidermal growth factor receptors (EGFRs) and or cancer that has abnormal DNA repair system.

## Claims

### Claim 1

A compound having the structure of Formula I:
wherein: R1 is selected from the group consisting of:
where n is 0, 1, 2, 3, or 4;
R2 is selected from the group consisting of: —H, —CH3, —OCH3, —NO2 and a halogen,
R3 is selected from the group consisting of: —H, —CH3, —OCH3, and a halogen,
R4 is selected from the group consisting of: —H, —CH3, —OCH3, —NO2, and a halogen,
R5 is selected from the group consisting of: —H, —CH3, —OCH3, and a halogen,
R6 is selected from the group consisting of: —H, and a halogen,
R7 is selected from the group consisting of: —H, and a halogen,
R8 is a halogen, and
R9 is selected from the group consisting of: —H, and a halogen,
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R8 consists of Cl.

### Claim 3 (depends on 1)

The compound of claim 1, wherein R8 consists of F.

### Claim 4 (depends on 1)

The compound of claim 1, wherein R8 consists of Br.

### Claim 5 (depends on 1)

A method of synthesizing the compound of claim 1, having the structure of Formula II:
comprising the following reaction steps:

### Claim 6 (depends on 1)

The compound of claim 1, further comprising a pharmaceutically acceptable carrier.

### Claim 7 (depends on 6)

The compound of claim 6, further comprising at least one additional anti-cancer agent selected from the group consisting of: a conventional chemotherapeutic agent, a protein kinase inhibitor, a topoisomerase inhibitor, a mitotic kinesin inhibitor, a histone deacetylase inhibitor, a mTOR inhibitor, a growth factor inhibitor, a growth factor receptor inhibitor, a transcriptional factor inhibitor, an anticancer monoclonal antibody, and glucocorticoid hormones for the simultaneous, separate, or sequential treatment of cancer.

### Claim 8 (depends on 7)

The compound of claim 7, wherein the conventional chemotherapeutic agent is selected from the group consisting of: an alkylating agent, an anti-metabolitic agent, an antibiotic, an anti-tubule agent, and an anti-hormonal agent.

### Claim 9 (depends on 7)

The compound of claim 7, wherein the conventional chemotherapeutic agent is selected from the group consisting of: mechlorethamine, cyclophosphamide, Busulfan, chlorambucil, leukeran, paraplatin, cisplatin, carboplatin, platinol, Methotrexate (MTX), 6-mercaptopurine (6-MP), cytarabine (Ara-C), floxuridine (FUDR), fluorouracil, hydroxyurea (Hydrea), etoposide (VP16), actinomycin D, bleomycin, mithramycin, daunorubicin, paclitaxel, and its derivatives, vinca and its derivatives, bicalutamide, Flutamide, Tamoxifen, and Megestrol.

### Claim 10 (depends on 7)

The compound of claim 7, wherein the protein kinase inhibitor is selected from the group consisting of: inhibitors of cyclin-dependent kinases, tyrosine kinases, phosphoinositide 3-kinase PI3K/AKT, protein kinase C, casein kinases, MAP kinases, and Src kinases.

### Claim 11 (depends on 7)

The compound of claim 7, wherein the protein kinase inhibitor is selected from the group consisting of: midostaurin, 7-hydroxystaurosporine, bryostatin 1, perifosine, ilmofosine, Ro 31-8220, Ro 32-0432, GO 6976, ISIS-3521, macrocyclic bis (indolyl) maleimides, AZD9291, and erlotinib.

### Claim 12 (depends on 7)

The compound of claim 7, wherein the anticancer monoclonal antibody is selected from the group consisting of: Cetuximab, Herceptin, and Bevacizumab.

### Claim 13 (depends on 7)

The compound of claim 7, wherein the glucocorticoid hormone is selected from the group consisting of: dexamethasone, prednisone, prednisolone, metyylprednisolone, and hydrocoritisone.

### Claim 14 (depends on 7)

The compound of claim 7, wherein the at least one additional anti-cancer agent is paclitaxel, or its derivative.

### Claim 15 (depends on 1)

A method for inhibiting proliferation of a cell having abnormal epidermal growth factor receptor (EGFR) activity, abnormal DNA repair system, or both, comprising: administering to the cell having abnormal epidermal growth factor receptor (EGFR) activity a therapeutically effective amount of the compound of claim 1.

### Claim 16 (depends on 15)

The method of claim 15, further comprising administering at least one additional anti-cancer agent selected from the group consisting of: a conventional chemotherapeutic agent, a protein kinase inhibitor, a topoisomerase inhibitor, a mitotic kinesin inhibitor, a histone deacetylase inhibitor, a mTOR inhibitor, a growth factor inhibitor, a growth factor receptor inhibitor, a transcriptional factor inhibitor, an anticancer monoclonal antibody, and glucocorticoid hormones.

### Claim 17 (depends on 15)

The method of claim 15, wherein the cell having abnormal epidermal growth factor receptor (EGFR), abnormal DNA repair system, or both is a human cancer cell.

### Claim 18 (depends on 17)

The use of claim 17, wherein the cancer is selected from the group consisting of: breast cancer, ovarian cancer, epithelial ovarian cancer, lung adenocarcinoma, and prostate cancer.

### Claim 19 (depends on 15)

The method of claim 15, wherein step of administering to the cell having abnormal epidermal growth factor receptor (EGFR) or abnormal DNA repair system is done by administering to a subject having abnormal epidermal growth factor receptor (EGFR) cells or having abnormal DNA repair system.

### Claim 20 (depends on 19)

The method of claim 19, wherein the subject is human and the compound is administered orally, topically, or parenterally to the subject in need thereof.