Dihydropyrene derivatives, processes for preparing the same and their uses

Patent metadata

Field	Value
Publication number	US-10501632-B2
Application number	US-201615577784-A
Country	US
Kind code	B2
Filing date	Jun 3, 2016
Priority date	Jun 4, 2015
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

Abstract

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

First claim

The invention claimed is:

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,
R 1 and R′ 1 represent independently from each other:

H,
a linear or branched (C 1 -C 18 )-alkyl,
a (C 3 -C 8 )-cycloalkyl,

—N(R) 3 + ,
R representing:
H,
a linear or branched (C 1 -C 18 )-alkyl,
a (C 3 -C 8 )-cycloalkyl,
R 2 , R 3 , R 4 and R 5 represent independently from each other:

H,
a linear or branched (C 1 -C 18 )-alkyl,
a (C 3 -C 8 )-cycloalkyl,

—N(R) 3 + ,
R representing:
H,
a linear or branched (C 1 -C 18 )-alkyl,
a (C 3 -C 8 )-cycloalkyl,
X represents one or more physiologically acceptable counter anion(s),

providing that:
at least one of R 1 , R′ 1 , R 2 , R 3 , R 4 and R 5 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.

2. The method according to claim 1 wherein:
R 1 and R′ 1 are identical;
R 1 and/or R′ 1 represent(s) a linear or branched (C 1 -C 18 )-alkyl, in particular a tert-butyl;
R 2 and/or R 4 represent(s)

R 3 and R 5 representing in particular H;
R 3 and/or R 5 represent(s)

R 2 and R 4 representing in particular H; or
X is (are) chosen from the group consisting in Cl − , PF 6 − , BF 4 − , CH 3 COO − , Br − , F − , SO 4 2− , HSO 4 − , HPO 4 2− , H 2 PO 4 − ; or
R represents a linear or branched (C 1 -C 18 )-alkyl, in particular —CH 3 .

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

4. 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.

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

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,
R 1 and R′ 1 represent independently from each other:

H,
a linear or branched (C 1 -C 18 )-alkyl,
a (C 3 -C 8 )-cycloalkyl,

—N(R) 3 + ,
R representing:
H,
a linear or branched (C 1 -C 18 )-alkyl,
a (C 3 -C 8 )-cycloalkyl,
R 2 , R 3 , R 4 and R 5 represent independently from each other:

H,
a linear or branched (C 1 -C 18 )-alkyl,
a (C 3 -C 8 )-cycloalkyl,

—N(R) 3 + ,
R representing:
H,
a linear or branched (C 1 -C 18 )-alkyl,
a (C 3 -C 8 )-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 R 1 , R′ 1 , R 2 , R 3 , R 4 and R 5 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.

7. Compound according to claim 6 , wherein:
R 1 and R′ 1 are identical;
R 1 and/or R′ 1 represent(s) a linear or branched (C 1 -C 18 )-alkyl, in particular a tert-butyl;
R 2 and/or R 4 represent(s)

R 3 and R 5 representing in particular H;
R 3 and/or R 5 represent(s)

R 2 and R 4 representing in particular H;
X is (are) chosen from the group consisting in Cl − , PF 6 − , BF 4 − , CH 3 COO − , Br − , F − , SO 4 2− , HSO 4 − , HPO 4 2− , H 2 PO 4 − ; or
R represents a linear or branched (C 1 -C 18 )-alkyl, in particular —CH 3 .

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

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

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

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

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

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

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,
R 1 and R′ 1 represent independently from each other:

H,
a linear or branched (C 1 -C 18 )-alkyl,
a (C 3 -C 8 )-cycloalkyl,

Assignees

• Univ Grenoble Alpes

Inventors

• Royal Guy
• Cobo Saioa
• Saint-Aman Eric
• Josserand Veronique
• Boturyn Didier

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61K47/545

  Heterocyclic compounds (A61K47/558 takes precedence) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K49/0015

  Phosphorescence · CPC title

• A61K47/61

  the organic macromolecular compound being a polysaccharide or a derivative thereof · CPC title