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Substituted porphyrinsRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Heavy Metal Containing (including Salts), Polycyclo Ring SystemSubstituted porphyrins description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070179124, Substituted porphyrins. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO REALTED APPLICATIONS [0001] This application is a continuation of application Ser. No. 11/127,302, filed May 12, 2005, which is a continuation of application Ser. No. 09/880,125, filed Jun. 14, 2001, now U.S. Pat. No. 6,916,799, which is a continuation of application Ser. No. 09/184,982, filed Nov. 3, 1988, now abandoned, which claims the benefit under 35 U.S.C. .sctn.119(e) of U.S. Provisional Patent Application Ser. No. 60/064,116, filed Nov. 3, 1997, now expired. Each of the foregoing applications is incorporated by reference herein in its entirety. TECHNICAL FIELD [0002] 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 [0003] 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. [0004] 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.sub.2.sup.- into H.sub.2O.sub.2 plus O.sub.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-Sob) 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 .alpha.-tocopherol (Halliwell et al, Arch. Biochem. Biophys. 280:l (1990)). [0005] 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 [0006] 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. The substituted porphyrins are also expected to have activity as antibacterial and antiviral agents, and as ionophores and chemotherapeutics. Objects and advantages of the present invention will be clear from the description that follows. BRIEF DESCRIPTION OF THE DRAWINGS [0007] FIG. 1. Mechanism. [0008] FIG. 2. Manganese meso-tetrakis-N-alkyl-pyridinium based porphyrins. [0009] FIG. 3. SOD activity in vivo (E. coli) of 1, 2, 3* and 4* (20 .mu.M) in minimal medium (mixture of atropoisomers, JI=SOD deficient strain, AB=parental strain). [0010] FIG. 4. Structures of MnCl.sub.xTE-2-PyP.sup.5+(x=1 to 4). [0011] FIG. 5. .sup.1H-NMR spectrum (porphyrin ring) of H.sub.2Cl.sub.2aT-2-PyP in CDCl.sub.3 (.delta.=7.24 ppm). The four protons in alpha position of the four pyridyl nitrogens are taken as integration reference. [0012] FIG. 6. Plot of the free energy of activation (.DELTA.G.degree.) for the O.sub.2.sup.31 dismutation reaction catalyzed by MnCl.sub.xTE-2-PyP.sup.5+ as a function of the ground state free energy change (.DELTA.G.degree.) for MnCl.sub.xTE-2-PyP.sup.5- redox. .DELTA.G.degree. and .DELTA.G.degree. were calculated from k.sub.cat and E.degree..sub.1/2 values reported in Table 4 (F, R, h and k.sub.B are Faraday, molar gas, Planck and Boltzmann constants, respectively). Numbers 0-4 correspond to x in MnCl.sub.xTE-2-PyP.sup.5- Corresponding data for one active site of Cu,Zn-SOD (Ellerby et al, J. Am. Chem. Soc. 118:6556 (1996)). [0013] FIG. 7. Illustrated are the chemical structures of three classes of antioxidants. A) The meso-porphyrin class is depicted where: R.sub.1 is either a benzoic acid (tetrakis-(4-benzoic acid) porphyrin (TBAP)) or a N-methyl group in the 2 or 4 position of the pyridyl (tetrakis-(N-methyl pyridinium-2(4)-yl) porphyrin (TM-2-PyP, TM-4-PyP)); R.sub.2 is either a hydrogen (H) or a bromide (Br, OBTM-4-PyP) and where the porphyrin is ligated with either a manganese (Mn), cobalt (Co), iron (Fe), or zinc (Zn) metal. B) The vitamin E analog class is represented by trolox. C) The flavanoid class is represented by rutin. [0014] FIG. 8. The time course of iron/ascorbate mediated oxidation of rat brain homogenates. Rat brain homogenates were incubated for various times with 0.25 .mu.M FeCl.sub.2 and 1 .mu.M ascorbate, and lipid peroxidation was measured as thiobarbituric acid reactive species (TBARS) spectrophotometrically at 535 nm (n=3). [0015] FIG. 9. The comparison of trolox (.box-solid.), rutin (.tangle-solidup.), bovine CuZnSOD (.circle-solid.), MnOBTM-4-PyP () and MnTM-2-PyP (.diamond-solid.) in their ability to inhibit iron/ascorbate mediated oxidation of rat brain homogenates. Rat brain homogenates were incubated for 30 minutes with 0.25 .mu.M FeCl.sub.2 and 1 .mu.M ascorbate, and lipid peroxidation was measured as thiobarbituric acid reactive species. The amount of TBARS formed in 30 minutes was expressed as 100% lipid peroxidation (n=3-6). Sigmoidal dose response curves were derived from fitting the data to a non-linear regression program. [0016] FIG. 10. The comparison of manganic (.tangle-solidup.), cobalt (.circle-solid.), iron () and zinc (.box-solid.) analogs of TBAP in their ability to inhibit iron/ascorbate mediated oxidation of rat brain homogenates. Rat brain homogenates were incubated for 30 minutes with 0.25 .mu.M FeCl.sub.2 and 1 .mu.M ascorbate, and lipid peroxidation was measured as thiobarbituric acid reactive species. The amount of TBARS formed in 30 minutes was expressed as 100% lipid peroxidation (n=3-6). Sigmoidal dose response curves were derived from fitting the data to a non-linear regression program. [0017] FIG. 11. The comparison of manganic (solid) and zinc (open) analogs of TM-4-PyP (squares) and TM-2-PyP (triangles) in their ability to inhibit iron/ascorbate mediated oxidation of rat brain homogenates. Rat brain homogenates were incubated for 30 minutes with 0.25 .mu.M FeCl.sub.2 and 1 .mu.M ascorbate, and-lipid peroxidation was measured as thiobarbituric acid reactive species. The amount of TBARS formed in 30 minutes was expressed as 100% lipid peroxidation (n=3-6). Sigmoidal dose response curves were derived from fitting the data to a non-linear regression program. DETAILED DESCRIPTION OF THE INVENTION [0018] The present invention relates to methods of protecting against the deleterious effects of oxidants, particularly, superoxide radicals, hydrogen peroxide and peroxynitrite, and to methods of preventing and treating diseases and disorders that involve or result from oxidant stress. The invention also relates methods of modulating biological processes involving oxidants, including superoxide radicals, hydrogen peroxide, nitric oxide and peroxynitrite. The invention further relates to compounds and compositions, including low molecular weight antioxidants (eg mimetics of scavengers of reactive oxygen species, including mimetics of SODs, catalases and peroxidases) and formulations thereof, suitable for use in such methods. Continue reading about Substituted porphyrins... Full patent description for Substituted porphyrins Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Substituted porphyrins patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Substituted porphyrins or other areas of interest. ### Previous Patent Application: Methods and compositions for treating diseases associated with pathogenic proteins Next Patent Application: 2-carbamide-4-phenylthiazole derivatives, preparation thereof and therapeutic use thereof Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Substituted porphyrins patent info. 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