De novo synthesis of bacteriochlorins

Patent metadata

Field	Value
Publication number	US-9822123-B2
Application number	US-201414162201-A
Country	US
Kind code	B2
Filing date	Jan 23, 2014
Priority date	Feb 18, 2005
Publication date	Nov 21, 2017
Grant date	Nov 21, 2017

Abstract

A method of making a bacteriochlorin is carried out by condensing a pair of compounds of Formula II

to produce the bacteriochlorin, wherein R is an acetal or aldehyde group. The condensing may be carried out in an organic solvent, preferably in the presence of an acid. The bacteriochlorins are useful for a variety of purposes such as active agents in photodynamic therapy, luminescent compounds in flow cytometry, solar cells, light harvesting arrays, and molecular memory devices.

First claim

That which is claimed is:

1. A compound of Formula I:

wherein:
M is a metal or is absent;
X is NH;
R 1 and R 2 are each independently selected from the group consisting of H, alkyl, aryl, alkoxy, halo, mercapto, cyano, hydroxyl, nitro, acyl, alkylthio, alkylamino, acyloxy, linking groups, and —C(O)NR a R b where R a and R b are each independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl and aryl;
R 3 and R 4 are each independently selected from the group consisting of alkyl, cycloalkyl, aryl, arylalkyl, and linking groups;
R 5 is selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, alkoxy, halo, cyano, nitro, acyl, alkylthio, alkylamino, arylalkylamino, disubstituted amino, acylamino, acyloxy, linking groups, and —C(O)NR a R b where R a and R b are each independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl and aryl;
R 6 and R 7 are each independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, halo, cyano, nitro, acyl, alkoxy, alkylthio, alkylamino, arylalkylamino, disubstituted amino, acylamino, acyloxy, linking groups, —C(O)NR a R b where R a and R b are each independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl and aryl, —C(O)OR c where R c is selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl and aryl, and C(O)OH; and
R 8 is selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, halo, cyano, nitro, acyl, alkoxy, alkylthio, alkylamino, arylalkylamino, disubstituted amino, acylamino, acyloxy, linking groups, and —C(O)NR a R b where R a and R b are each independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl and aryl;
or R 1 and R 2 together are ═O or spiroalkyl;
or R 3 and R 4 together are ═O or spiroalkyl;
subject to the proviso that (i) neither R 1 nor R 2 is H, or (ii) neither R 3 nor R 4 is H; and further
subject to the proviso that, when X is NH:
R 1 is not cycloalkyl; or
R 2 is not methyl; or
R 5 is not H; or
R 6 is not H; or
R 7 is not methyl.

2. The compound of claim 1 , wherein R 1 is not cycloalkyl.

3. The compound of claim 1 , wherein R 2 is not methyl.

4. The compound of claim 1 , wherein R 5 is not H.

5. The compound of claim 1 , wherein R 6 is not H.

6. The compound of claim 1 , wherein R 7 is not methyl.

7. The compound of claim 1 , wherein M is present and is selected from the group consisting of Pd, Pt, Mg, Zn, Al, Ga, In, Sn, Cu, Ni, and Au.

8. The compound of claim 1 , wherein at least one of R 1 through R 8 is a linking group.

9. The compound of claim 1 , wherein at least one of R 6 , R 7 , or R 8 is a linking group.

10. A compound of claim 1 coupled to a hydrophilic group.

11. A compound of claim 1 coupled to a hydrophilic group at least one of said R 6 , R 7 , or R 8 positions.

12. A compound of claim 1 coupled to a targeting agent.

13. A compound of claim 1 coupled to a targeting agent at least one of said R 6 , R 7 , or R 8 positions.

14. A compound of claim 1 coupled to an antibody.

15. A compound of claim 1 coupled to an antibody at least one of said R 6 , R 7 , or R 8 positions.

16. A compound of claim 1 coupled to a protein or peptide.

17. A compound of claim 1 coupled to a protein or peptide at least one of said R 6 , R 7 , or R 8 positions.

18. A compound of claim 1 coupled to a nucleic acid.

19. A compound of claim 1 coupled to a nucleic acid at least one of said R 6 , R 7 , or R 8 positions.

20. A composition consisting of a compound of claim 1 , wherein:
said composition has a peak molar absorption coefficient in solution of 10,000 to 300,000 M −1 cm −1 at a wavelength between 650 and 900 nanometers; and
said composition has a loss of not more than 20 percent of said compound when stored in a sealed vessel at room temperature in the absence of ambient light for at least 3 months.

21. A composition comprising a compound of claim 1 in a solvent, wherein
said composition has a peak molar absorption coefficient in solution of 10,000 to 300,000 M −1 cm −1 at a wavelength between 650 and 900 nanometers; and
said composition has a loss of not more than 20 percent of said compound when stored in a sealed vessel at room temperature in the absence of ambient light for at least 3 months.

22. A pharmaceutical composition comprising a compound of claim 1 in a pharmaceutically acceptable carrier.

23. The pharmaceutical composition of claim 22 , wherein said carrier comprises an aqueous carrier.

24. The pharmaceutical composition of claim 22 , wherein said carrier comprises an organic solvent.

25. The pharmaceutical composition of claim 22 , wherein:
said composition has a peak molar absorption coefficient in solution of 10,000 to 300,000 M −1 cm −1 at a wavelength between 650 and 900 nanometers; and
said composition has a loss of not more than 20 percent of said compound when stored in a sealed vessel at room temperature in the absence of ambient light for at least 3 months.

Assignees

• Univ North Carolina State

Inventors

• Kim Han-Je
• Lindsey Jonathan S

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P39/02

  Antidotes · CPC title

• A61P31/10

  Antimycotics · CPC title

• A61P31/04

  Antibacterial agents · CPC title