# US 10,501,632 B2 · Dihydropyrene derivatives, processes for preparing the same and their uses

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- Number: US 10,501,632 B2
- Document ID: US10501632B2
- Status: Granted
- Kind: B2
- Application number: 15/577,784
- Filed: 2016-06-03
- Published: 2018-05-10
- Granted: 2019-12-10
- Earliest claimed: 2015-06-04
- Assignees: Universite Grenoble Alpes
- Applicants: Universite Grenoble Alpes
- Inventors: Guy Royal; Saioa Cobo; Eric Saint-Aman; Veronique Josserand; Didier Boturyn
- Web page: https://patentgrep.com/patent/US10501632B2

## CPC

- C09B 57/001: {Pyrene dyes}
- 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}
- A61K 47/545: {Heterocyclic compounds (A61K47/558 takes precedence)}
- A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61K 49/0015: {Phosphorescence}
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- C07D 213/06: containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D 213/20: Quaternary compounds thereof
- C07D 493/08: Bridged systems
- C09B: ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES {, e.g. PIGMENTS}; MORDANTS; LAKES (fermentation or enzyme using processes to synthesise a desired chemical compound C12P)
- 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

Disclosed are dihydropyrene derivatives, processes for preparing the same and their uses.

## Claims

### Claim 1

A method for treating pathologies sensitive to singlet oxygen, in particular for phototherapy and/or for treating cancers comprising administering to a subject in need thereof a compound of the following formula I
wherein:
n represents 0 or 1,
represents a single bond or no bond,
represents a single or a double bond,
R1 and R′1 represent independently from each other:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
—N(R)3+,
R representing:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
R2, R3, R4 and R5 represent independently from each other:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
—N(R)3+,
R representing:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
X represents one or more physiologically acceptable counter anion(s),
providing that:
at least one of R1, R′1, R2, R3, R4 and R5 represents one of the following groups:
or
—N(R)3+,
n, and the bonds 1 to 7 are such as:
n=0, represents a single bond, bonds 1, 4 and 6 represent a double bond, and bonds 2, 3, 5 and 7 represent a single bond, or
n=0, represents no bond, bonds 1, 3, 5 and 7 represent a double bond, and bonds 2, 4 and 6 represent a single bond, or
n=1, represents no bond, bonds 2, 5 and 7 represent a double bond, and bonds 1, 3, 4 and 6 represent a single bond.

### Claim 2 (depends on 1)

The method according to claim 1 wherein:
R1 and R′1 are identical;
R1 and/or R′1 represent(s) a linear or branched (C1-C18)-alkyl, in particular a tert-butyl;
R2 and/or R4 represent(s)
R3 and R5 representing in particular H;
R3 and/or R5 represent(s)
R2 and R4 representing in particular H; or
X is (are) chosen from the group consisting in Cl−, PF6−, BF4−, CH3COO−, Br−, F−, SO42−, HSO4−, HPO42−, H2PO4−; or
R represents a linear or branched (C1-C18)-alkyl, in particular —CH3.

### Claim 3 (depends on 1)

The method according to claim 1 wherein the compound is one of the compound of the following formulae:

### Claim 4 (depends on 1)

The method according to claim 1, wherein the compound of formula I forms a complex of the following formula II
B group being chosen from a peptide or an acid residue selected from a hyaluronic acid or a folic acid.

### Claim 5 (depends on 1)

A pharmaceutical or diagnostic composition comprising a compound of formula I according to claim 1 as active agent and a pharmaceutically acceptable vehicle.

### Claim 6

Compound of the following formula I (bis)
wherein:
n is 1,
represents a single bond or no bond,
represents a single or a double bond,
R1 and R′1 represent independently from each other:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
—N(R)3+,
R representing:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
R2, R3, R4 and R5 represent independently from each other:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
—N(R)3+,
R representing:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
X represents one or more counter anion(s), in particular one or more physiologically acceptable counter anion(s),
providing that:
at least one of R1, R′1, R2, R3, R4 and R5 represents one of the following groups:
or
—N(R)3+f
n, and the bonds 1 to 7 are such as:
n=1, represents no bond, bonds 2, 5 and 7 represent a double bond, and bonds 1, 3, 4 and 6 represent a single bond.

### Claim 7 (depends on 6)

Compound according to claim 6, wherein:
R1 and R′1 are identical;
R1 and/or R′1 represent(s) a linear or branched (C1-C18)-alkyl, in particular a tert-butyl;
R2 and/or R4 represent(s)
R3 and R5 representing in particular H;
R3 and/or R5 represent(s)
R2 and R4 representing in particular H;
X is (are) chosen from the group consisting in Cl−, PF6−, BF4−, CH3COO−, Br−, F−, SO42−, HSO4−, HPO42−, H2PO4−; or
R represents a linear or branched (C1-C18)-alkyl, in particular —CH3.

### Claim 8 (depends on 7)

Compound according to claim 7, of one of the following formulae:

### Claim 9 (depends on 1)

A pharmaceutical or diagnostic composition comprising a compound of formula I according to claim 1 as active agent and a pharmaceutically acceptable vehicle.

### Claim 10 (depends on 2)

A pharmaceutical or diagnostic composition comprising a compound of formula I according to claim 2 as active agent and a pharmaceutically acceptable vehicle.

### Claim 11 (depends on 3)

A pharmaceutical or diagnostic composition comprising a compound of formula I according to claim 3 as active agent and a pharmaceutically acceptable vehicle.

### Claim 12 (depends on 4)

A pharmaceutical or diagnostic composition comprising a complex of formula II according to claim 4 as active agent and a pharmaceutically acceptable vehicle.

### Claim 13 (depends on 4)

The method according to claim 4, wherein the B group is a peptide of the following formula:

### Claim 14

A compound of the following formula I (bis)
wherein:
n represents 0 or 1,
represents a single bond or no bond,
represents a single or a double bond,
R1 and R′1 represent independently from each other:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
—N(R)3+,
R representing:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
R2, R3, R4 and R5 represent independently from each other:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
—N(R)3+,
R representing:
H,
a linear or branched (C1-C18)-alkyl,
a (C3-C8)-cycloalkyl,
X represents one or more counter anion(s), in particular one or more physiologically acceptable counter anion(s),
providing that:
at least one of R1, R′1, R2, R3, R4 and R5 represents one of the following groups:
or
—N(R)3+,
n, and the bonds 1 to 7 are such as:
n=0, represents a single bond, bonds 1, 4 and 6 represent a double bond, and bonds 2, 3, 5 and 7 represent a single bond, or
n=0, represents no bond, bonds 1, 3, 5 and 7 represent a double bond, and bonds 2, 4 and 6 represent a single bond, or
n=1, represents no bond, bonds 2, 5 and 7 represent a double bond, and bonds 1, 3, 4 and 6 represent a single bond,
when n=0, R1 and/or R′1 are different from one of the following groups:
or
—N(R)3+,
wherein the compound of formula I(bis) forms a complex of the following formula II(bis)
II (bis)
B group being chosen from a peptide or an acid residue selected from a hyaluronic acid or a folic acid.

### Claim 15 (depends on 14)

The compound according to claim 14, wherein:
R1 and R′1 are identical;
R1 and/or R′1 represent(s) a linear or branched (C1-C18)-alkyl, in particular a tert-butyl;
R2 and/or R4 represent(s)
R3 and R5 representing in particular H;
R3 and/or R5 represent(s)
R2 and R4 representing in particular H;
X is (are) chosen from the group consisting in Cl−, PF6−, BF4−, CH3COO−, Br−, F−, SO42−, HSO4−, HPO42−, H2PO4−; or
R represents a linear or branched (C1-C18)-alkyl, in particular —CH3.

### Claim 16 (depends on 14)

The compound according to claim 14, of one of the following formulae:

### Claim 17 (depends on 14)

The compound according to claim 14, wherein the B group is a peptide of the following formula: