# US 8,541,476 B2 · Compounds for treatment of malignant tumors

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- Number: US 8,541,476 B2
- Document ID: US8541476B2
- Status: Granted
- Kind: B2
- Application number: 12/677,478
- Filed: 2008-09-12
- Published: 2011-08-04
- Granted: 2013-09-24
- Earliest claimed: 2007-09-14
- Assignees: The Trustees of the University of Pennsylvania; Wake Forest University Health Sciences; University of the Sciences in Philadelphia
- Applicants: Constantinos Koumenis; Brian E. Lally; Steven Kridel; Gary D. Kao; Adeboye Adejare
- Inventors: Constantinos Koumenis; Brian E. Lally; Steven Kridel; Gary D. Kao; Adeboye Adejare
- Web page: https://patentgrep.com/patent/US8541476B2

## CPC

- A61K 31/12: Ketones
- A61K 31/10: Sulfides; Sulfoxides; Sulfones
- A61K 31/275: Nitriles; Isonitriles
- A61K 31/662: Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K 41/0038: {Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10)}
- 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

The present invention comprises compounds, compositions and methods of use for sensitizing cancer cells, tumors, neoplasms, and malignancies to the effects of ionizing radiation used in the treatment of cancer. The invention further comprises a method of identifying novel radiosensitizing compounds.

## Claims

### Claim 1

A method of treating a mammal diagnosed with cancer, said method comprising administering to said mammal a therapeutically effective amount of a pharmacological composition comprising a compound of formula (I):
wherein:
Y is NO2, NR13, CN, CHO, C(O)R1 or CF3;
X is H, F, Cl, Br or I;
R is CN, CHO, C(O)R1, C(O)NH2, C(O)NHR1, C(O)NR1R2, S(O)mR1, S(O)2NH2, S(O)2NHR1, S(O)2NR1R2, P(O)(OH)R1, C(O)OH, or C(O)OR1;
R1 and R2 each independently is CH3, CH2CH3, CH2CH2CH3, CH2CH2CH2CH3, CH(CH3)2, or C(CH3)3; and
m is an integer of 0, 1 or 2;
or a pharmaceutically acceptable salt,
wherein said composition contacts a cancer cell or tumor in said mammal, thereby making said cancer cell or tumor more susceptible to the effects of ionizing radiation,
wherein said cancer is at least one selected from the group consisting of glioma, colorectal cancer and non-small cell lung cancer.

### Claim 2 (depends on 1)

The method of claim 1, wherein said composition is administered before, during, or after said mammal receives radiation therapy, or a combination thereafter.

### Claim 3 (depends on 1)

The method of claim 1, wherein said mammal is a human.

### Claim 4

A method of treating a mammal diagnosed with cancer, said method comprising administering to said mammal a therapeutically effective amount of a composition comprising Formula I,
wherein Y═NO2, R═C(O)R1, R1═CH2CH3, and X═I, or a pharmaceutically acceptable salt thereof,
wherein said composition contacts a cancer cell or tumor in said mammal, thereby making said cancer cell or tumor more susceptible to the effects of ionizing radiation,
wherein said cancer is at least one selected from the group consisting of glioma, colorectal cancer and non-small cell lung cancer.

### Claim 5 (depends on 4)

The method of claim 4, wherein said composition is administered before, during, or after said mammal receives radiation therapy, or a combination thereafter.

### Claim 6 (depends on 4)

The method of claim 4, wherein said mammal is a human.

### Claim 7

A method of treating a mammal diagnosed with cancer, said method comprising administering to said mammal a therapeutically effective amount of a composition comprising Formula I,
wherein Y═NO2, R═S(O)2R1, R1═CH2CH3, and X═F or I, or a pharmaceutically acceptable salt thereof,
wherein said composition contacts a cancer cell or tumor in said mammal, thereby making said cancer cell or tumor more susceptible to the effects of ionizing radiation
wherein said cancer is at least one selected from the group consisting of glioma, colorectal cancer and non-small cell lung cancer.

### Claim 8 (depends on 7)

The method of claim 7, wherein said composition is administered before, during, or after said mammal receives radiation therapy, or a combination thereafter.

### Claim 9 (depends on 7)

The method of claim 7, wherein said mammal is a human.

### Claim 10

A method of treating a mammal diagnosed with cancer, said method comprising administering to said mammal a therapeutically effective amount of a composition comprising Formula I,
Y═NO2, R═P(O)(OH)R1, R1═CH2CH3, and X═F, Cl, Br, H, or I, or a pharmaceutically acceptable salt thereof,
wherein said composition contacts a cancer cell or tumor in said mammal, thereby making said cancer cell or tumor more susceptible to the effects of ionizing radiation,
wherein said cancer is at least one selected from the group consisting of glioma, colorectal cancer and non-small cell lung cancer.

### Claim 11 (depends on 10)

The method of claim 10, wherein said composition is administered before, during, or after said mammal receives radiation therapy, or a combination thereafter.

### Claim 12 (depends on 10)

The method of claim 10, wherein said mammal is a human.