Substituted porphyrins

• US 20040023941A1
• Filed: 01/23/2003
• Published: 02/05/2004
• Est. Priority Date: 01/25/1999
• Status: Active Grant

• Current Assignee: Duke University, National Jewish Health
• Original Assignee: Aeolus Pharmaceuticals, Inc., Duke University, National Jewish Medical and Research Center
• Inventors: Kitchen, Douglas B., Day, Brian J., Fridovich, Irwin, Trova, Michael P., Batinic-Haberle, Ines, Crapo, James D., Gauuan, Polivina Jolicia F.
• Granted Patent: US 7,189,707 B2
• Time in Patent Office: Days
• US Class Current: 514/185
• CPC Class Codes: A61K 31/409 having four such rings, e.g. porphine derivatives, bilirubin, biliverdine hemin, hematin A61K31/555
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C09B 47/00 Porphines; Azaporphines non-dyeing compounds C07D487/22

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

2. The compound according to claim 1 wherein R₁ and Rare the same and are:

3. The compound according to claim 2 wherein X is methyl or ethyl.

4. The compound according to claim 1 wherein R₁, R₂, R₃ and R₄ are the same.

5. The compound according to claim 1 wherein R₁, R₂, R₃ and R₄ are

6. The compound according to claim 5 wherein X is methyl or ethyl.

7. The compound according to claim 5 wherein R₁, R₂, R₃ and R₄ are the same.

8. The compound according to claim 7 wherein R₁, R₂, R₃ and R₄ are

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

10. The compound according to claim 9 wherein said compound is complexed with manganese.

11. A method of protecting cells from oxidant-induced toxicity comprising contacting said cells with a protective amount of a compound of formula

12. The method according to claim 11 wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.

13. The method according to claim 12 wherein said metal is manganese.

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

15. The method according to claim 14 wherein said cells are cells of an isolated organ.

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

17. 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 a compound of formula

18. The method according to claim 17 wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.

19. The method according to claim 18 wherein said compound is complexed with manganese.

20. A method of treating a pathological condition of a patient resulting from degradation of NOor a biologically active form thereof, comprising administering to said patient an effective amount of a compound of formula

21. The method according to claim 20 wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.

22. The method according to claim 21 wherein said compound is complexed with manganese.

23. A method of treating a patient for an inflammatory disease comprising administering to said patient an effective amount of a compound of formula

24. The method according to claim 23 wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.

25. The method according to claim 24 wherein said compound is complexed with manganese.

26. The method according to claim 23 wherein said inflammatory disease is an inflammatory lung disease.

27. The method according to claim 26 wherein said inflammatory lung disease is bronchopulmonary disease.

28. The method according to claim 26 wherein said inflammatory lung disease is asthma.

29. The method according to claim 26 wherein said inflammatory lung disease is pulmonary fibrosis.

30. A method of treating a patient for an ischemic reperfusion injury comprising administering to said patient an effective amount of a compound of formula

31. The method according to claim 30 wherein said compound is complexed with a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel or zinc.

32. The method according to claim 31 wherein said compound is complexed with manganese.

33. The method according to claim 30 wherein said ischemic reperfusion injury results from a stroke.