Fluorinated photosensitizers related to chlorins and bacteriochlorins for photodynamic therapy

• US RE43,274 E1
• Filed: 01/23/2009
• Issued: 03/27/2012
• Est. Priority Date: 06/27/2002
• Status: Expired due to Fees

• Current Assignee: Health Research Incorporated
• Original Assignee: Health Research Incorporated
• Inventors: Pandey, Ravindra K., Potter, William R., Dougherty, Thomas J.
• Primary Examiner(s): Wilson, James O
• Assistant Examiner(s): McDowell, Brian
• Application Number:
  US12/321,729
• Time in Patent Office: 1,159 Days
• Field of Search: 540/145
• US Class Current: 424/9.362
• CPC Class Codes: A61K 41/0071 PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• CPC Class Codes: A61K 41/0076 PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
• CPC Class Codes: C07D 471/22 in which the condensed systems contains four or more hetero rings
• CPC Class Codes: C09B 47/00 Porphines; Azaporphines non-dyeing compounds C07D487/22
• CPC Class Codes: C09B 69/108 containing a phthalocyanine dye

Abstract

Provided herein are compounds for detection, diagnosis and treatment of target tissues or target compositions, including hyperproliferative tissues such as tumors, using photodynamic methods. In particular, photosensitizer compounds that collect in hyperproliferative tissue are provided. In another embodiment, compounds that absorb light at a wavelength of from about 700 to about 850 nm are provided. In a further embodiment, compounds that are detectable by magnetic resonance imaging are provided.

Claims

1. A compound of the formula:

2. The compound of claim 1, wherein:

R₁ is methyl;

R_1a and R_2a together form a covalent bond;

R₃ is methyl;

R₄ is ethyl;

R_3a and R_4a are each independently hydrogen, or together form a covalent bond;

R₅ is methyl;

R₉ is CH₂CH₂COOH or CH₂CH₂COOMe;

R₁₀ is methyl.

3. The compound of claim 1, wherein:

R₂ is CH═

CH₂, CH(OR₂₀)CH₃, C(O)Me, C(═

NR₂₁)CH₃ or CH(NHR₂₁)CH₃;

where R₂₀ is methyl, butyl, heptyl, dodecyl or 3,5-bis(trifluoromethyl)benzyl; and

R₂₁ is 3,5-bis(trifluoromethyl)benzyl.

4. The compound of claim 1 having the formula:

5. The compound of claim 1 having the formula:

6. The compound of claim 1 having the formula:

7. The compound of claim 1 having the formula:

8. The compound of claim 1 having the formula:

9. The compound of claim 1 having the formula:

10. The compound of claim 1 having the formula:

11. The compound of claim 1 having the formula

12. The compound of claim 1 having the formula:

13. The compound of claim 1 having the formula

14. The compound of claim 1 having the formula:

15. The compound of claim 1 having the formula

16. A pharmaceutical composition, comprising a compound of claim 1 or a pharmaceutically acceptable derivative thereof in a pharmaceutically acceptable carrier.

17. The compound of claim 10 or a pharmaceutically acceptable derivative thereof when used for the detection or treatment or both of hyperproliferative tissue.

18. The compound of claim 11 or a pharmaceutically acceptable derivative thereof when used for the detection or treatment or both of hyperproliferative tissue.

19. The compound of claim 12 or a pharmaceutically acceptable derivative thereof when used for the detection or treatment or both of hyperproliferative tissue.

20. A compound of the formula:

21. The compound of claim 20 wherein:

R₁ is methyl;

R_1a and R_2a together form a covalent bond;

R₃ is methyl;

R₄ is ethyl;

R_3a and R_4a are each independently hydrogen, or together form a covalent bond;

R₅ is methyl;

R₉ is CH₂CH₂COOMe;

R₁₀ is methyl.

22. The compound of claim 20, wherein:

R₂ is CH═

CH₂, C(O)Me, C(═

NR₂₁)CH₃, CH(NHR₂₁)CH₃, and R₂₁ is 3,5-bis(trifluoromethyl)benzyl.

34. A pharmaceutical composition, comprising a compound of claim 20 in a pharmaceutically acceptable carrier.

23. A compound having the formula:

24. A compound having the formula:

25. A compound having the formula:

26. A compound having the formula:

27. A compound having the formula:

28. A compound having the formula:

29. A compound having the formula:

30. A compound having the formula:

31. A compound having the formula:

32. A compound having the formula:

33. A compound having the formula: