Multicyclic nitrone spin trapping compositions

Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

540450, 540451, A61K 4900, G01N 3100, G01N 3348

Patent

active

059002271

ABSTRACT:
Multicyclic nitrone spin trapping compounds capable of forming stable free radical spin adducts are provided as well as methods for their synthesis. The multicyclic nitrone spin trapping compounds can be reacted with a free radical, such as a hydroxy or hydroperoxy radical, in solution to form a spin adduct which is stable and readily detectable by electron paramagnetic resonance (EPR) spectroscopy. The multicyclic nitrone spin traps can be used to detect free radicals in a sample such as a biological system. In one embodiment, the spin trapping compound, provided, as well as methods for the synthesis of TRAZON and of modified forms of TRAZON. TRAZON can react with a wide range of different free radicals in solution to form free radical spin adducts which are readily detectable by EPR.

REFERENCES:
patent: 3296145 (1967-01-01), Findlam et al.
patent: 3849934 (1974-11-01), Dorschner et al.
patent: 4153722 (1979-05-01), Campbell et al.
patent: 4197314 (1980-04-01), Campbell et al.
patent: 4214003 (1980-07-01), Campbell et al.
patent: 4216231 (1980-08-01), Tanida
patent: 4224340 (1980-09-01), Campbell et al.
patent: 4870002 (1989-09-01), Kiel
patent: 5036097 (1991-07-01), Floyd et al.
patent: 5681845 (1997-10-01), Janzen et al.
Baethmann, et al., "Mediators of Brain Edema and Secondary Brain Damage", Critical Care Medicine, 16(10):972-977 (1988).
Bancroft, et al., "Spin Trapping with Covalently Immobilized 84(5):557-558 (1980).
Bapat & Black, "Nitrones and Oxaziridines, I. Preparation of I-Pyrroline I-Oxides and I-Pyrroline By Reductive Cyclization of .gamma.-Nitro Carbonyl Compounds", Aust. J. Chem., 21:2483-2495 (1968).
Barasch, et al., "Novel DMPO-Derived .sup.13 C-Labeled Spin Traps Yield Identifiable Stable Nitroxides", J. Am. Chem. Soc., 116:7319-7324 (1994).
Black & Blackman, "Nitrones and Oxaziridines. XXV* Bromination of 2-t-Butyl- and 2-Phenyl-1-pyrroline 1-Oxides", Aust. J. Chem., 32:1795-1803 (1979).
Black & Boscacci, "Nitrones and Oxaziridines, XV Approaches to 3-Oxo-I-Pyrroline I-Oxides by Oxidation of I-Pyrroline I-Oxides", Aust. J. Chem., 29:3511 (1976).
Bolli & McCay, "Use of Spin Traps in Intact Animals Undergoing Myocardial Ischemia/Reperfusion: A New Approach to Assessing the Role of Oxygen Radicals in Myocardial `Stunning`," Free Rad. Res. Comms., 9(3-6):169-180 (1990).
Bolli, et al., "Demonstration of Free Radical Generation in "Stunned" Myocardium of Intact Dogs with the Use of the Spin Trap .alpha.-Phenyl N-Tert-Butyl Nitrone", J. Clin. Invest., 82:476-485 (1988).
Bonnett, et al., "Experiments Towards the Synthesis of Corrins, Part II, The Preparation and Reactions of I-Pyrroline 1-Oxides", J. Chem. Soc., 2094-2102 (1959).
Buettner & Oberly, "Considerations in the Spin Trapping of Superoxide and Hydroxyl Radical in Aqueous Systems Using 5,5-Dimethyl-I-pyrroline-I-oxide", Biochem. Biophys. Res. Com., 83:69 (1978).
Buettner, "The Syringe Nitroxide Free Radical-Part II", Free Rad. Res. Commun., 19(S1):S228-S230 (1993).
Carney, et al., "Protection Against Oxidative Damage to CNS by .alpha.-Phenyl-tert-Butyl Nitrone (PBN) and Other Spin-Trapping Agents: A Novel Series of Nonlipid Free Radical Scavengers" J. Mol. Neurosci., 3:47-57(1990).
Carney, et al., "Reversal of Age-related Increase in Brain Protein Oxidation, Decrease in Enzyme Activity, and Loss in Temporal and Spatial Memory by Chronic Administration of the Spin-Trapping Compound N-tert-Butyl-.alpha.-Phenylnitrone", Proc. Natl. Acad. Sci. USA, 88:3633-3636 (1991).
Chandler, et al., "An Unanesthetized-Gerbil Model of Cerebral Ischemia-induced Behavioral Changes", J. Pharm. Methods, 14:137-146 (1985).
Chen, et al., "Excretion, Metabolism and Tissue Distribution of a Spin-Trapping Agent, .alpha.-Phenyl-N-Tert-Butyl-Nitrone (PBN in Rats," Free Rad. Res. Comms., 9(3-6):317-323 (1990).
Chiu, et al, "Effect of Catalase and/or Allopurinol, or N-t-Butyl-.alpha.-Phenylnitrone on Hepatic Ischemia", Transplantation Proceedings, XIX(I):1077-1079 (1987).
Curran, et al., "Viral and Cellular for Proteins Are Complexed with a 39,000-Dalton Cellular Protein", Mol. Cell Biol., 5:167-172 (1985).
Degray & Mason, "Biological Spin Trapping", Electron Spin Resonance, Chapter 8, 246-319 (?).
Ernster, "Biochemistry of Reoxygenation Injury", Critical Care Medicine, 16(10):947-953 (1988).
Finkelstein, et al., "Spin Trapping. Kinetics of the Reaction of Superoxide and Hydroxyl Radicals with Nitrones", J. Am. Chem. Soc., 102:4994-4999 (1980).
Finkelstein, et al., "Spin Trapping of Superoxide", Mol. Pharmacol., 16:676 (1979).
Finkelstein, et al., Spin Trapping of Superoxide and Hydroxyl Radical: Practical Aspects.sup.1, Arch. Biochem. and Biophys., 200(1)1-16 (1980).
Floyd, et al., "Age Influence on Oxidative Events During Brain Ischemia/Reperfusion", Arch. Gerontol. Geriatr., 12:155-177 (1991).
Frejaville, et al., "5-Diethoxyphosphoryl-5-methyl-1-pyrroline N-Oxide (DEPMPO): A New Phosphorylated Nitrone for the Efficient In Vitro and In Vivo Spin Trapping of Oxygen-centered Radicals", J. Chem. Soc., Chem. Commun., 1793-1794 (1994).
Gelvan, et al., "Cardiac Reperfusion Damage Prevented by a Nitroxide Free Radical," Proc. Natl. Acad. Sci. USA, 88(11):4680-4684 (Jun. 1, 1991).
Giercksky, et al., "Epidemiology of NSAID-Related Gastrointestinal Side Effects," Scand. J. Gastroenterology, 3-7 (1989).
Haire, et al., "The First H and N ENDOR Spectra of An Oxygen-Centered Radical Adduct of DMPQ-type Nitrones", Can. J. Chem., 66:7395 (1988).
Haire, et al., "A More Efficient Synthesis of DMPO-Type (Nitrone) Spin Traps", J. Org. Chem., 51:4298-4300 (1986).
Haire, et al., "NMR Solvent Effect Study of Pyrroline-N-Oxide Spin Traps: Microenvironments in Sodium Dodecyl Sulfate Micelles", Magnetic Res. Chemistry, 33:1-7 (1995).
Haire & Janzen, "Synthesis and Spin Trapping Kinetics of New Alkyl Substituted Cyclic Nitrones", Can. J. Chem., 60:1514-1522 (1982).
Hall, et al., "Correlation Between Attenuation of Postraumatic Spinal Cord Ischemia and Preservation of Tissue Vitamin E by the 21-Aminosteroid U74006E: Evidence for an In Vivo Antioxidant Mechanism", J. of Neurotrauma, 6(3):169-176 (1989).
Hall, "Free Radicals and CNS Injury" Critical Care Clinics, 5(4):793-805 (1989).
Halliwell & Gutteridge, Free Radicals in Biology and Medicine, Second Edition., Oxford, Clarendon Press, 1989.
Hamburger, et al., "Endotoxin-Induced Mortality in Rats is Reduced by Nitrones", Circulatory Shock, 29:329-334 (1989).
Harbour, et al., An Electron Spin Resonance Study of the Spin Adducts of OH and HO.sub.2, Can. J. Chem., 52:3549 (1974).
Hearse & Tosaki, "Reperfusion-Induced Arrhythmias and Free Radicals: Studies in the Rat Heart with DMPO," J. Cardiovasc. Pharmacol., 9(6):641-650 (1987).
Hearse, et al., "Free Radicals and Reperfusion-Induced Arrhythmias: Protection by Spin Trap Agent PBN in the Rat Heart", Circulation Research, 60(3):375-383 (1987).
Hearse, et al., "Free Radicals and Calcium: Simultaneous Interacting Triggers as Determinants of Vulnerability to Reperfusion-Induced Arrhythmias in the Rat Heart" J. Mol. Cell. Cardiol., 20:213-223 (1988).
Hillman & Bloom, "Economic Effects of Prophylactic Use of Misoprostol to Prevent Gastric Ulcer in Patients Taking Nonsteroidal Anti-inflammatory Drugs," Arch. Intern. Med. 149:2061-2065 (1989).
Hossman, "Resuscitation Potentials After Prolonged Global Cerebral Ischemia in Cats", Critical Care Medicine, 16(10):964-971 (1988).
Ilieva, et al., "Noradrenaline and Adrenaline in the Adrenal Glands and Myocardiun During Endotoxin Shock and Antioxidant Therapy", Neurosciences, 12:223-227 (1986) (abstract).
Janzen & Liu, "Radical Addition Reactions of 5,5-Dimethyl-1-pyrroline-1-oxide. ESR Spin Trapping with a Cyclic Nitrone", Journal of Magnetic Resonance, 9(3):510-512 (1973).
Janzen, et al., "Factors Influencing Hyperfine Splitting in the ESR Spectra of Five-Membered Ring Nitroxides", Journal of Magnetic Resonance, 9:513-516 (1973).
Janzen, et al., "New 2-Substituted Pyrroline-N-oxides: An EPR Solvent Study of the Radical Spin Adducts", Magnetic Resonance Chem., 32:711-720 (1994).
Janzen & Zhang, "Identification of Reactive Free Ra

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Multicyclic nitrone spin trapping compositions does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Multicyclic nitrone spin trapping compositions, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Multicyclic nitrone spin trapping compositions will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-1868459

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.