# US 10,864,273 B2 · Thiobase compounds for photodynamic therapy

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- Number: US 10,864,273 B2
- Document ID: US10864273B2
- Status: Granted
- Kind: B2
- Application number: 16/573,682
- Filed: 2019-09-17
- Published: 2020-01-09
- Granted: 2020-12-15
- Earliest claimed: 2015-01-21
- Assignees: Case Western Reserve University
- Applicants: Case Western Reserve University
- Inventors: Carlos E. Crespo-Hernandez; Marvin Pollum
- Web page: https://patentgrep.com/patent/US10864273B2

## CPC

- A61K 41/0057: {Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent}
- A61N 5/062: {Photodynamic therapy, i.e. excitation of an agent}
- A61N 2005/0659: {infrared}
- A61N 2005/0661: {ultraviolet}
- A61N 2005/0662: {Visible light}
- 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)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)

## Abstract

A method of using a compound in a phototherapy procedure includes administering to a subject in need of treatment a therapeutically effective amount of a thio-substituted nucleobase, nucleoside, nucleotide, and/or analogs thereof; and exposing the administered compound to electromagnetic radiation.

## Claims

### Claim 1

A method of using a compound in a phototherapy procedure, the method comprising:
administering to a subject in need of treatment a therapeutically effective amount of compound having the formula:
or pharmaceutically acceptable salts thereof;
wherein R1 is H, OH, ribose, deoxyribose, amino acid residue(s), fatty acid residue(s), ORa, where Ra comprises at least one of a straight chain, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, arylsulfonyl, or aralkylsulfonyl, or a mono, di, or triphosphate thereof,
R2 and R3 are independently the same or different and are each selected from the group consisting of a H, F, Cl, Br, I, a lower alkyl group, (CH2)n1OR′ (wherein n1=1, 2, or 3), CF3, CH2—CH2X, O—CH2—CH2X, CH2—CH2—CH2X, O—CH2—CH2X (wherein X═F, Cl, Br, or I), CN, (C═O)—R′, N(R′)2, NO2, (C═O)N(R′)2, O(CO)R′, OR′, SR′, COOR′ (wherein R′ is H or a lower alkyl group), or a substituted or unsubstituted aryl, heteroaryl, cycloalkyl, or heterocyclyl, and wherein R2 and R3 if present may be linked to form a cyclic or polycyclic ring, wherein the ring is a substituted or unsubstituted aryl, heteroaryl, cycloalkyl, or heterocyclyl; and
exposing the administered compound to electromagnetic radiation.

### Claim 2 (depends on 1)

The method of claim 1 wherein the compound absorbs electromagnetic radiation having wavelengths from about 300 nm to about 1400 nm.

### Claim 3 (depends on 1)

The method of claim 1, wherein the compound is exposed to ultraviolet radiation to cause localized cell death or injury.

### Claim 4 (depends on 1)

The method of claim 1, wherein the compound is selected from the group consisting of:
and pharmaceutically acceptable salts thereof,
wherein R1 is H, OH, ribose, deoxyribose, amino acid residue(s), fatty acid residue(s), ORa, where Ra comprises at least one of a straight chain, branched or cylclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, arylsulfonyl, or aralkylsulfonyl, or a mono, di, or triphosphate thereof.

### Claim 5 (depends on 1)

The method of claim 1, wherein exposing the administered compound to electromagnetic radiation generates a therapeutically effective amount of reactive intermediates causing localized cell death or injury.

### Claim 6 (depends on 1)

The method of claim 1, wherein the procedure comprises contacting a target tissue of the subject with the administered compound.

### Claim 7 (depends on 6)

The method of claim 6, wherein the target tissue is a colon, prostate, gastric, esophageal, uterine, endometrial, pancreatic, breast, cervical, brain, skin, gallbladder, lung, throat, kidney, testicular, prostrate, gastric, or ovary tissue.

### Claim 8 (depends on 6)

The method of claim 6, wherein the target tissue is cancerous tissue.

### Claim 9 (depends on 6)

The method of claim 6, wherein the target tissue is a tumor.

### Claim 10 (depends on 1)

The method of claim 1, for use in treatment of cancer or a cancer-associated disorder, wherein the cancer or cancer-associated disorder is colon cancer, prostate cancer, gastric cancer, esophageal cancer, uterine cancer, endometrial cancer, pancreatic cancer, breast cancer, cervical cancer, brain cancer, skin cancer, gall bladder cancer, lung cancer, or ovarian cancer.

### Claim 11 (depends on 1)

The method of claim 1, for use in treatment of an inflammation-associated disorder.

### Claim 12

A method of treating cancer or a cancer-associated disorder in a subject in need thereof, the method comprising:
administering to a subject in need of treatment a therapeutically effective amount of compound having the formula:
or pharmaceutically acceptable salts thereof;
wherein R1 is H, OH, ribose, deoxyribose, amino acid residue(s), fatty acid residue(s), ORa, where Ra comprises at least one of a straight chain, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, arylsulfonyl, or aralkylsulfonyl, or a mono, di, or triphosphate thereof,
R2 and R3 are independently the same or different and are each selected from the group consisting of a H, F, Cl, Br, I, a lower alkyl group, (CH2)n1OR′ (wherein n1=1, 2, or 3), CF3, CH2—CH2X, O—CH2—CH2X, CH2—CH2—CH2X, O—CH2—CH2X (wherein X═F, Cl, Br, or I), CN, (C═O)—R′, N(R′)2, NO2, (C═O)N(R′)2, O(CO)R′, OR′, SR′, COOR′ (wherein R′ is H or a lower alkyl group), or a substituted or unsubstituted aryl, heteroaryl, cycloalkyl, or heterocyclyl, and wherein R2 and R3 if present may be linked to form a cyclic or polycyclic ring, wherein the ring is a substituted or unsubstituted aryl, heteroaryl, cycloalkyl, or a heterocyclyl; and
exposing the administered compound to electromagnetic radiation effective to treat the cancer or cancer-associated disorder.

### Claim 13 (depends on 12)

The method of claim 12 wherein the compound absorbs electromagnetic radiation having wavelengths from about 300 nm to about 1400 nm.

### Claim 14 (depends on 12)

The method of claim 12, wherein the compound is exposed to ultraviolet radiation to cause localized cell death or injury.

### Claim 15 (depends on 12)

The method of claim 12, wherein the compound is selected from the group consisting of:
and pharmaceutically acceptable salts thereof;
wherein R1 is H, OH, ribose, deoxyribose, amino acid residue(s), fatty acid residue(s), ORa, where Ra comprises at least one of a straight chain, branched or cylclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, arylsulfonyl, or aralkylsulfonyl, or a mono, di, or triphosphate thereof.

### Claim 16 (depends on 12)

The method of claim 12, wherein exposing the administered compound to electromagnetic radiation generates a therapeutically effective amount of reactive intermediates causing localized cell death or injury.

### Claim 17 (depends on 12)

The method of claim 12, for use in treatment of cancer or a cancer-associated disorder, wherein the cancer or cancer-associated disorder is colon cancer, prostate cancer, gastric cancer, esophageal cancer, uterine cancer, endometrial cancer, pancreatic cancer, breast cancer, cervical cancer, brain cancer, skin cancer, gall bladder cancer, lung cancer, or ovarian cancer.