Tetrapyrroles

• US 20030069281A1
• Filed: 06/14/2001
• Published: 04/10/2003
• Est. Priority Date: 06/14/2000
• Status: Abandoned Application

• Current Assignee: Duke University, Goodnow Capital, L.L.C., National Jewish Medical and Research Center
• Original Assignee: Goodnow Capital, L.L.C.
• Inventors: Day, Brian J., Fridovich, Irwin, Batinic-Haberle, Ines, Crapo, James D., Spasojevic, Ivan
• Application Number:
  US09/880,075
• Publication Number:
  US 20030069281A1
• Time in Patent Office: Days
• US Class Current: 514/340
• CPC Class Codes: C07D 207/456 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more hetero rings

Abstract

The present invention relates, in general, to a method of modulating physiological and pathological processes and, in particular, to a method of modulating cellular levels of oxidants and thereby processes in which such oxidants are a participant. The invention also relates to compounds and compositions suitable for use in such methods.

Claims

1. A compound of formula

3. The compound according to claim 1 or 2 wherein R₁ through R₈ are, independently, —

962 H, C₁-C₅ alkyl, 2-hydroxy C₁-C₅ alkyl, C₁-C₅alkyl ester of C₁-C₅carboxylic acid, C₁-C₅carboxylic acid, glucuronyl or glyceryl ester of C₁-C₅carboxylic acid, 1,2-dihydroxy C₁-C₅ alkyl, acetyl, vinyl, glycosyl, taurate, chloro, fluoro, bromo, nitro, cyano, trimethylammonium, or formyl, and

β

, γ

and δ

are, independently, —

H, acetyl, glycyl, benzoato, phenylsulfonato, 2-, 3- or 4—

N—

C₁-C₅ alkyl-pyridyl, nitrophenyl, bromo-, chloro- or fluorophenyl or 2-, 3- or 4—

N—

C₁-C₅alkylsulfonatopyridyl.

4. The compound according to claim 1 or 2 wherein said compound is complexed with a metal selected from the group consisting of zinc, iron, nickel, cobalt, copper, manganese.

5. The compound according to claim 4 wherein said compound is complexed with manganese.

6. A dimeric form of the compound according to claim 4.

7. The dimer according to claim 6 wherein said metal is manganese.

8. The dimer according to claim 7 wherein said dimer is of the formula:

9. A method of protecting cells from oxidant-induced toxicity comprising contacting said cells with a protective amount of the compound according to claim 1 or 2 so that said protection is effected.

10. The method according to claim 9 wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.

11. The method according to claim 10 wherein said metal is manganese.

12. The method according to claim 11 wherein said cells are mammalian cells.

13. The method according to claim 12 wherein said cells are cells of an isolated organ.

14. The method according to claim 13 wherein said cells are cells of an organ transplant.

15. A method of treating a patient suffering from a condition that results from or that is exacerbated by oxidant-induced toxicity comprising administering to said patient an effective amount of the compound according to claim 1 or 2 so that said treatment is effected.

16. The method according to claim 15 wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.

17. The method according to claim 16 wherein said compound is complexed with manganese.

18. A method of treating a pathological condition of a patient resulting from the production or accumulation of a degradation product of NO or a biologically active form thereof, comprising administering to said patient an effective amount of the compound according to claim 1 or 2 so that said treatment is effected.

19. The method according to claim 18 wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.

20. The method according to claim 19 wherein said compound is complexed with manganese.

21. A method of treating a patient for an inflammatory disease comprising administering to said patient an effective amount of the compound according to claim 1 or 2 so that said treatment is effected.

22. The method according to claim 21 wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.

23. The method according to claim 22 wherein said compound is complexed with manganese.

24. A method of treating a patient for an ischemic reperfusion injury comprising administering to said patient an effective amount of the compound according to claim 1 or 2 so that said treatment is effected.

25. The method according to claim 24 wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.

26. The method according to claim 25 wherein said compound is complexed with manganese.

27. The method according to claim 24 wherein said ischemic reperfusion injury results from a stroke.

2. A compound of formula