Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-04-23
2002-11-12
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S410000, C540S145000
Reexamination Certificate
active
06479477
ABSTRACT:
TECHNICAL FIELD
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.
BACKGROUND
Oxidants are produced as part of the normal metabolism of all cells but also are an important component of the pathogenesis of many disease processes. Reactive oxygen species, for example, are critical elements of the pathogenesis of diseases of the lung, the central nervous system and skeletal muscle. Oxygen free radicals also play a role in modulating the effects of nitric oxide (NO.). In this context, they contribute to the pathogenesis of vascular disorders, inflammatory diseases and the aging process.
A critical balance of defensive enzymes against oxidants is required to maintain normal cell and organ function. Superoxide dismutases (SODs) are a family of metalloenzymes that catalyze the intra- and extracellular conversion of O
2
−
into H
2
O
2
plus O
2
, and represent the first line of defense against the detrimental effects of superoxide radicals. Mammals produce three distinct SODs. One is a dimeric copper- and zinc-containing enzyme (CuZn SOD) found in the cytosol of all cells. A second is a tetrameric manganese-containing SOD (Mn SOD) found within mitochondria, and the third is a tetrameric, glycosylated, copper- and zinc-containing enzyme (EC-SOD) found in the extracellular fluids and bound to the extracellular matrix. Several other important antioxidant enzymes are known to exist within cells, including catalase and glutathione peroxidase. While extracellular fluids and the extracellular matrix contain only small amounts of these enzymes, other extracellular antioxidants are also known to be present, including radical scavengers and inhibitors of lipid peroxidation, such as ascorbic acid, uric acid, and &agr;-tocopherol (Halliwell et al, Arch. Biochem. Biophys. 280:1 (1990)).
The present invention relates generally to low molecular weight porphyrin compounds suitable for use in modulating intra- and extracellular processes in which superoxide radicals, or other oxidants such as hydrogen peroxide or peroxynitrite, are a participant. The compounds and methods of the invention find application in various physiologic and pathologic processes in which oxidative stress plays a role.
SUMMARY OF THE INVENTION
The present invention relates to a method of modulating intra- or extracellular levels of oxidants such as superoxide radicals, hydrogen peroxide, peroxynitrite, lipid peroxides, hydroxyl radicals and thiyl radicals. More particularly, the invention relates to a method of modulating normal or pathological processes involving superoxide radicals, hydrogen peroxide, nitric oxide or peroxynitrite using low molecular weight antioxidants, and to methine (ie, meso) substituted porphyrins suitable for use in such a method.
Objects and advantages of the present invention will be clear from the description that follows.
REFERENCES:
patent: 2951799 (1960-09-01), Sharp
patent: 4614723 (1986-09-01), Schmidt
patent: 4746735 (1988-05-01), Kruper, Jr. et al.
patent: 4758422 (1988-07-01), Quay
patent: 4837221 (1989-06-01), Bonnett
patent: 4851403 (1989-07-01), Picker et al.
patent: 4885114 (1989-12-01), Gordon et al.
patent: 4892941 (1990-01-01), Dolphin et al.
patent: 4895719 (1990-01-01), Radhakrishnam
patent: 5171680 (1990-08-01), Mullenbach et al.
patent: 4963367 (1990-10-01), Ecanow
patent: 5051337 (1991-09-01), Sakoda et al.
patent: 5130245 (1992-07-01), Marklund et al.
patent: 5162519 (1992-11-01), Bonnett
patent: 5169630 (1992-12-01), Okaya et al.
patent: 5202317 (1993-04-01), Bruice
patent: 5217966 (1993-06-01), Bruice
patent: 5223538 (1993-06-01), Fridovich
patent: 5227405 (1993-07-01), Fridovich
patent: 5236914 (1993-08-01), Meunier
patent: 5236915 (1993-08-01), Fiel
patent: 5248603 (1993-09-01), Marklund et al.
patent: 5262532 (1993-11-01), Tweedle et al.
patent: 5281616 (1994-01-01), Dixon et al.
patent: 5284647 (1994-02-01), Niedballa
patent: 5366729 (1994-11-01), Marklund et al.
patent: 5472691 (1995-12-01), Marklund et al.
patent: 5493017 (1996-02-01), Therien et al.
patent: 5599924 (1997-02-01), Therien et al.
patent: 5674467 (1997-10-01), Maier et al.
patent: 5747026 (1998-05-01), Crapo
patent: 5994339 (1999-11-01), Crapo et al.
patent: 6046188 (2000-04-01), Malfroy-Camine et al.
patent: 6084093 (2000-07-01), Riley et al.
patent: 6103714 (2000-08-01), Fridovich et al.
patent: 6127356 (2000-10-01), Crapo et al.
patent: 0 127 797 (1984-12-01), None
patent: 0 186 962 (1986-07-01), None
patent: 0 282 899 (1988-09-01), None
patent: 0 336 879 (1989-10-01), None
patent: 0 337 601 (1989-10-01), None
patent: 0 345 171 (1989-12-01), None
patent: 0 414 915 (1991-03-01), None
patent: 0 462 836 (1991-12-01), None
patent: 0 524 161 (1993-01-01), None
patent: 0 532 327 (1993-03-01), None
patent: 2 676 738 (1992-11-01), None
patent: WO 91/04315 (1991-04-01), None
patent: WO 92/07935 (1992-05-01), None
patent: WO 92/15099 (1992-09-01), None
patent: WO 93/02090 (1993-02-01), None
patent: WO 94/04614 (1994-03-01), None
patent: WO 95/10185 (1995-04-01), None
patent: WO 95/31197 (1995-11-01), None
patent: WO 9609038 (1996-03-01), None
patent: WO 96/09053 (1996-03-01), None
patent: WO 96/40223 (1996-12-01), None
patent: WO 98/33503 (1998-06-01), None
patent: WO 99/23097 (1999-05-01), None
patent: WO 99/55388 (1999-11-01), None
patent: WO 00/43395 (2000-07-01), None
patent: WO 01/26655 (2001-04-01), None
patent: WO 01/96345 (2001-12-01), None
Collman et al. J. Am. Chem. Soc. 103(3) (1981) 516-533.*
Batinić -Haberle Arch. Biochem. Biophys. 343(2) (1997) 225-233.*
Comhair et al. Lancet 355(9204) (2000) 624 (Medline abstract).*
Rosenfeld et al. Pediatrics 6 (1996) 811-817 (Medline abstract).*
Lee et al. J. Chem. Soc., Perkin Trans. 1 (1997) 1215.*
Freeman and Crapo, “Biology of disease: free radicals and tissue injury”, Lab. Invest. 47(5):412-426 (1982)—Abstract.
Pietarinen et al, “Catalase and glutathione reductase protection of human alveolar macrophages during oxidant exposure in vitro”, Am. J. Respir. Cell Mol. Biol. 13(4):434-441 (1995)—Abstract.
Poli, G., “Pathogenesis of liver fibrosis” role of oxidative stress”, Mol. Aspects Med. 21(3):49-98 (2000)—Abstract.
Delanty and Dichter, “Antioxidant therapy in neurologic disease”, Arch. Neurol. 57(9):1265-1270 (2000)—Abstract.
Smith et al, “Oxidative stress in Alzheimer's disease”, Biochim. Biophy. Acta 1502(1):139-144 (2000)—Abstract.
Zalba et al, “Vascular oxidant stress: molecular mechanisms and pathophysiological implications”, J. Physiol. Biochem. 56(1):57-64 (2000)—Abstract.
Babior, B.M., “Phagocytes and oxidative stress”, Am. J. Med. 109(10:33-44 (2000)—Abstract.
Dhalla et al, “Status of myocardial antioxidants in ischemia-reperfusion injury”, Cardiovasc. Res. 47(3):446-456 (2000)—Abstract.
Dhalla et al, “Role of oxidative stress in cardiovascular diseases”, J. Hypertens. 18(6):655-673—Abstract (2000).
Sohal et al, “Current issues concerning the role of oxidative stress in aging: a perspective”, Results Probl. Cell Differ. 29:45-66 (2000)—Abstract.
Melov, S., “Mitochondrial oxidative stress. Physiologic consequences and potential for a role in aging”, Ann. N.Y. Acad. Sci. 908:219-225 (2000)—Abstract.
Laight et al, “Antioxidants, diabetes and endothelial dysfunction”, Cardiovasc. Res. 47(3):457-464 (2000)—Abstract.
Grune et al, “Oxidative stress in anemia”, Clin. Nephrol. 53(1 Suppl):S18-22 (2000)—Abstract.
Mates and Sanchez-Jimenez, “Role of reactive oxygen species in apoptosis: implications for cancer therapy”, Int. J. Biochem. Cell Biol. 32(2):157-170 (2000)—Abstract.
Mates et al, “Antioxidant enzymes and human diseases”, Clin. Biochem. 32(8):595-603 (1999)—Abstract.
Battino et al, “Oxidative injury and inflammatory periodontal diseases: the challenge of anti-oxidants to free radicals and reactive oxygen species”, Crit. Rev. Oral Biol. Med. 10(4):458
Crapo James D.
Day Brian J.
Gauuan Polivina Jolicia F.
Pechulis, Jr. Anthony D.
Trova Michael P.
Duke University
Raymond Richard L.
LandOfFree
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