Impact of the 3,6,9-trioxadecyloxy group on desazadesferrithiocin analogue iron clearance and organ distribution

Journal of Medicinal Chemistry

Volumn 50, Issue 14, 2007, Pages 3302-3313

  Bergeron, Raymond J ^a   Wiegand, Jan ^a   Bharti, Neelam ^a   Singh, Shailendra ^a   Rocca, James R ^a  

^a UNIVERSITY OF FLORIDA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4,5 DIHYDRO 2 [2 HYDROXY 3 (3,6,9 TRIOXADECYLOXY)PHENYL] 4 METHYL 4 THIAZOLECARBOXYLIC ACID; 4,5 DIHYDRO 2 [2 HYDROXY 4 (3,6,9 TRIOXADECYLOXY)PHENYL] 4 METHYL 4 THIAZOLECARBOXYLIC ACID; 4,5 DIHYDRO 2 [2 HYDROXY 5 (3,6,9 TRIOXADECYLOXY)PHENYL] 4 METHYL 4 THIAZOLECARBOXYLIC ACID; ALBUMIN; BENZOIC ACID; DEFERASIROX; DEFERIPRONE; DEFERITRIN; DEFEROXAMINE MESYLATE; DEFERRIFERRITHIOCIN; DESAZADESFERRITHIOCIN ANALOG; IRON CHELATING AGENT; IRON DEXTRAN; LIGAND; POLYETHER; TRANSFERRIN; UNCLASSIFIED DRUG;

ANEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATOMIC ABSORPTION SPECTROMETRY; BILE DUCT; CANNULATION; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL STRUCTURE; CONTROLLED STUDY; DRUG FECES LEVEL; DRUG URINE LEVEL; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IRON BALANCE; IRON CHELATION; IRON OVERLOAD; LIGAND BINDING; MALE; MONKEY; NEPHROTOXICITY; NONHUMAN; ORGAN DISTRIBUTION; PROTEIN BINDING; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; SPECIES DIFFERENCE; SYNTHESIS; TISSUE DISTRIBUTION;

ANIMALS; CEBUS; DIHYDROPYRIDINES; IRON; IRON CHELATING AGENTS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MASS SPECTROMETRY; RATS; RATS, SPRAGUE-DAWLEY; SPECIES SPECIFICITY; THIAZOLES; TISSUE DISTRIBUTION;

EID: 34447523769     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070214s     Document Type: Article

References (56)

1. Brittenham, G. M. Disorders of Iron Metabolism: Iron Deficiency and Overload. In Hematology: Basic Principles and Practice, 3rd ed.; Hoffman, R., Benz, E. J., Shattil, S. J., Furie, B., Cohen, H. J., et al., Eds.; Churchill Livingstone: New York, 2000; pp 397-428.
2. Olivieri, N. F.; Brittenham, G. M. Iron-chelating Therapy and the Treatment of Thalassemia. Blood 1997, 89, 739-761.
3. Vichinsky, E. P. Current Issues with Blood Transfusions in Sickle Cell Disease. Semin. Hematol. 2001, 38, 14-22.
4. Kersten, M. J.; Lange, R.; Smeets, M. E.; Vreugdenhil, G.; Roozendaal, K. J.; Lameijer, W.; Goudsmit, R. Long-Term Treatment of Transfusional Iron Overload with the Oral Iron Chelator Deferiprone (L1): A Dutch Multicenter Trial. Ann. Hematol. 1996, 73, 247-252.
5. Conrad, M. E.; Umbreit, J. N.; Moore, E. G. Iron Absorption and Transport. Am. J. Med. Sci. 1999, 318, 213-229.
6. Lieu, P. T.; Heiskala, M.; Peterson, P. A.; Yang, Y. The Roles of Iron in Health and Disease. Mol. Aspects Med. 2001, 22, 1-87.
7. Angelucci, E.; Brittenham, G. M.; McLaren, C. E.; Ripalti, M.; Baronciani, D.; Giardini, C.; Galimberti, M.; Polchi, P.; Lucarelli, G. Hepatic Iron Concentration and Total Body Iron Stores in Thalassemia Major. N. Engl. J. Med. 2000, 343, 327-331.
8. Bonkovsky, H. L.; Lambrecht, R. W. Iron-Induced Liver Injury. Clin. Liver Dis. 2000, 4, 409-429, vi-vii.
9. Pietrangelo, A. Mechanism of Iron Toxicity. Adv. Exp. Med. Biol. 2002, 509, 19-43.
10. Cario, H.; Holl, R. W.; Debatin, K. M.; Kohne, E. Insulin Sensitivity and β-Cell Secretion in Thalassaemia Major with Secondary Haemochromatosis: Assessment by Oral Glucose Tolerance Test. Eur. J. Pediatr. 2003, 162, 139-146.
11. Wojcik, J. P.; Speechley, M. R.; Kertesz, A. E.; Chakrabarti, S.; Adams, P. C. Natural History of C282Y Homozygotes for Hemochromatosis. Can. J. Gastroenterol. 2002, 16, 297-302.
12. Brittenham, G. M.; Griffith, P. M.; Nienhuis, A. W.; McLaren, C. E.; Young, N. S.; Tucker, E. E.; Allen, C. J.; Farrell, D. E.; Harris, J. W. Efficacy of Deferoxamine in Preventing Complications of Iron Overload in Patients with Thalassemia Major. N. Engl. J. Med. 1994, 331, 567-573.
13. Zurlo, M. G.; De Stefano, P.; Borgna-Pignatti, C.; Di Palma, A.; Piga, A.; Melevendi, C.; Di Gregorio, F.; Burattini, M. G.; Terzoli, S. Survival and Causes of Death in Thalassaemia Major. Lancet 1989, 2, 27-30.
14. Raymond, K. N.; Carrano, C. J. Coordination Chemistry and Microbial Iron Transport. Acc. Chem. Res. 1979, 12, 183-190.
15. Byers, B. R.; Arceneaux, J. E. Microbial Iron Transport: Iron Acquisition by Pathogenic Microorganisms. Met. Ions Biol. Syst. 1998, 35, 37-66.
16. Kalinowski, D. S.; Richardson, D. R. The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer. Pharmacol Rev. 2005, 57, 547-583.
17. Bergeron, R. J. Iron: A Controlling Nutrient in Proliferative Processes. Trends Biochem. Sci. 1986, 11, 133-136.
18. Theil, E. C.; Huynh, B. H. Ferritin Mineralization: Ferroxidation and Beyond. J. Inorg. Biochem. 1997, 67, 30.
19. Ponka, P.; Beaumont, C.; Richardson, D. R. Function and Regulation of Transferrin and Ferritin. Semin. Hematol. 1998, 35, 35-54.
20. Graf, E.; Mahoney, J. R.; Bryant, R. G.; Eaton, J. W. Iron-Catalyzed Hydroxyl Radical Formation. Stringent Requirement for Free Iron Coordination Site. J. Biol. Chem. 1984, 259, 3620-3624.
21. Halliwell, B. Free Radicals and Antioxidants: A Personal View. Nutr. Rev. 1994, 52, 253-265.
22. Halliwell, B. Iron, Oxidative Damage, and Chelating Agents. In The Development of Iron Chelators for Clinical Use; Bergeron, R. J., Brittenham, G. M., Eds.; CRC: Boca Raton, 1994; pp 33-56.
23. Koppenol, W. Kinetics and Mechanism of the Fenton Reaction: Implications for Iron Toxicity. In Iron Chelators: New Development Strategies; Badman, D. G., Bergeron, R. J., Brittenham, G. M., Eds.; Saratoga: Ponte Vedra Beach, FL, 2000; pp 3-10.
24. Babbs, C. F. Oxygen Radicals in Ulcerative Colitis. Free Radical Biol. Med. 1992, 13, 169-181.
25. Hazen, S. L.; d'Avignon, A.; Anderson, M. M.; Hsu, F. F.; Heinecke, J. W. Human Neutrophils Employ the Myeloperoxidase-Hydrogen Peroxide-Chloride System to Oxidize α-Amino Acids to a Family of Reactive Aldehydes. Mechanistic Studies Identifying Labile Intermediates along the Reaction Pathway. J. Biol. Chem. 1998, 273, 4997-5005.
26. Bergeron, R. J.; McManis, J. S.; Weimar, W. R.; Wiegand, J.; Eiler-McManis, E. Iron Chelators and Therapeutic Uses. In Burger's Medicinal Chemistry, 6th ed.; Abraham, D. A., Ed.; Wiley: New York, 2003; pp 479-561.
27. Brittenham, G. M. Iron Chelators and Iron Toxicity. Alcohol 2003, 30, 151-158.
28. Bickel, H.; Hall, G. E.; Keller-Schierlein, W.; Prelog, V.; Vischer, E.; Wettstein, A. Metabolic Products of Actinomycetes. XXVII. Constitutional Formula of Ferrioxamine B. Helv. Chim. Acta 1960, 43, 2129-2138.
29. Giardina, P. J.; Grady, R. W. Chelation Therapy in β-Thalassemia: An Optimistic Update. Semin. Hematol. 2001, 38, 360-366.
30. Pippard, M. J. Desferrioxamine-Induced Iron Excretion in Humans. Bailliere's Clin. Haematol. 1989, 2, 323-343.
31. Hoffbrand, A. V.; Al-Refaie, F.; Davis, B.; Siritanakatkul, N.; Jackson, B. F. A.; Cochrane, J.; Prescott, E.; Wonke, B. Long-Term Trial of Deferiprone in 51 Transfusion-Dependent Iron Overloaded Patients. Blood 1998, 91, 295-300.
32. Olivieri, N. F. Long-Term Therapy with Deferiprone. Acta Haematol. 1996, 95, 37-48.
33. Olivieri, N. F.; Brittenham, G. M.; McLaren, C. E.; Templeton, D. M.; Cameron, R. G.; McClelland, R. A.; Burt, A. D.; Fleming, K. A. Long-Term Safety and Effectiveness of Iron-Chelation Therapy with Deferiprone for Thalassemia Major. N. Engl. J. Med. 1998, 339, 417-423.
34. Richardson, D. R. The Controversial Role of Deferiprone in the Treatment of Thalassemia. J. Lab. Clin. Med. 2001, 137, 324-329.
35. Nisbet-Brown, E.; Olivieri, N. F.; Giardina, P. J.; Grady, R. W.; Neufeld, E. J.; Sechaud, R.; Rrebs-Brown, A. J.; Anderson, J. R.; Alberti, D.; Sizer, K. C.; Nathan, D. G. Effectiveness and Safety of ICL670 in Iron-Loaded Patients with Thalassaemia: a Randomised, Double-Blind, Placebo-Controlled, Dose-Escalation Trial. Lancet 2003, 361, 1597-1602.
36. Galanello, R.; Piga, A.; Alberti, D.; Rouan, M.-C.; Bigler, H.; Séchaud, R. Safety, Tolerability, and Pharmacokinetics of ICL670, a New Orally Active Iron-Chelating Agent in Patients with Transfusion-Dependent Iron Overload Due to β-Thalassemia. J. Clin. Pharmacol. 2003, 43, 565-572.
37. Cappellini, M. D. Iron-chelating therapy with the new oral agent ICL670 (Exjade). Best Pract. Res., Clin. Haematol 2005, 18, 289-298.
38. Exjade Prescribing Information, http://www.pharma.us.novartis.com/ product/pi/pdf/exjade.pdf (accessed May 2007).
39. Bergeron, R. J.; Wiegand, J.; McManis, J. S.; Vinson, J. R. T.; Yao, H.; Bharti, N.; Rocca, J. R. (S)-4,5-Dihydro-2-(2-hydroxy-4-hydroxyphenyl)-4- methyl-4-thiazolecarboxylic Acid Polyethers: A Solution to Nephrotoxicity. J. Med. Chem. 2006, 49, 2772-2783.
40. Bergeron, R. J.; Wiegand, J.; McManis, J. S.; Bussenius, J.; Smith, R. E.; Weimar, W. R. Methoxylation of Desazadesferrithiocin Analogues: Enhanced Iron Clearing Efficiency. J. Med. Chem. 2003, 46, 1470-1477.
41. Bergeron, R. J.; Wiegand, J.; McManis, J. S.; Bharti, N. The Design, Synthesis, and Evaluation of Organ-Specific Iron Chelators. J. Med. Chem. 2006, 49, 7032-7043.
42. Naegeli, H.-U.; Zähner, H. Metabolites of Microorganisms. Part 193. Ferrithiocin. Helv. Chim. Acta 1980, 63, 1400-1406.
43. Hahn, F. E.; McMurry, T. J.; Hugi, A.; Raymond, K. N. Coordination Chemistry of Microbial Iron Transport. 42. Structural and Spectroscopic Characterization of Diastereomeric Cr(III) and Co(III) Complexes of Desferriferrithiocin. J. Am. Chem. Soc. 1990, 112, 1854-1860.
44. Anderegg, G.; Räber, M. Metal Complex Formation of a New Siderophore Desferrithiocin and of Three Related Ligands. J. Chem. Soc., Chem. Commun. 1990, 1194-1196.
45. Bergeron, R. J.; Wiegand, J.; Dionis, J. B.; Egli-Karmakka, M.; Frei, J.; Huxley-Tencer, A.; Peter, H. H. Evaluation of Desferrithiocin and Its Synthetic Analogues as Orally Effective Iron Chelators. J. Med. Chem. 1991, 34, 2072-2078.
46. Bergeron, R. J.; Streiff, R. R.; Wiegand, J.; Vinson, J. R. T.; Luchetta, G.; Evans, K. M.; Peter, H.; Jenny, H.-B. A Comparative Evaluation of Iron Clearance Models. Ann. N. Y. Acad. Sci. 1990, 612, 378-393.
47. Bergeron, R. J.; Streiff, R. R.; Creary, E. A.; Daniels, R. D., Jr.; King, W.; Luchetta, G.; Wiegand, J.; Moerker, T.; Peter, H. H. A Comparative Study of the Iron-Clearing Properties of Desferrithiocin Analogues with Desferrioxamine B in a Cebus Monkey Model. Blood 1993, 81, 2166-2173.
48. Bergeron, R. J.; Wiegand, J.; McManis, J. S.; McCosar, B. H.; Weimar, W. R.; Brittenham, G. M.; Smith, R. E. Effects of C-4 Stereochemistry and C-4′ Hydroxylation on the Iron Clearing Efficiency and Toxicity of Desferrithiocin Analogues. J. Med. Chem. 1999, 42, 2432-2440.
49. Bergeron, R. J.; Wiegand, J.; McManis, J. S.; Weimar, W. R.; Park, J.-H.; Eiler-McManis, E.; Bergeron, J.; Brittenham, G. M. Partition-Variant Desferrithiocin Analogues: Organ Targeting and Increased Iron Clearance. J. Med. Chem. 2005, 48, 821-831.
50. Ostergaard, J.; Schou, C.; Larsen, C.; Heegaard, N. H. Evaluation of Capillary Electrophoresis-Frontal Analysis for the Study of Low Molecular Weight Drug-Human Serum Albumin Interactions. Electrophoresis 2002, 23, 2842-2853.
51. Bergeron, R. J.; Streiff, R. R.; Wiegand, J.; Luchetta, G.; Creary, E. A.; Peter, H. H. A Comparison of the Iron-Clearing Properties of 1,2-Dimethyl-3-hydroxypyrid-4-one, 1,2-Diethyl-3-hydroxypyrid-4-one, and Deferoxamine. Blood 1992, 79, 1882-1890.
52. Wood, J. K.; Milner, P. F.; Pathak, U. N. The Metabolism of Irondextran Given as a Total-Dose Infusion to Iron Deficient Jamaican Subjects. Br. J. Haematol 1968, 14, 119-129.
53. Bergeron, R. J.; Wiegand, J.; Brittenham, G. M. HBED: A Potential Alternative to Deferoxamine for Iron-Chelating Therapy. Blood 1998, 91, 1446-1452.
54. Bergeron, R. J.; Wiegand, J.; Wollenweber, M.; McManis, J. S.; Algee, S. E.; Ratliff-Thompson, K. Synthesis and Biological Evaluation of Naphthyldesferrithiocin Iron Chelators. J. Med. Chem. 1996, 39, 1575-1581.
55. Bergeron, R. J.; Wiegand, J.; Weimar, W. R.; McManis, J. S.; Smith, R. E.; Abboud, K. A. Iron Chelation Promoted by Desazadesferrithiocin Analogues: An Enantioselective Barrier. Chirality 2003, 15, 593-599.
56. Bergeron, R. J.; Wiegand, J.; Ratliff-Thompson, K.; Weimar, W. R. The Origin of the Differences in (R)- and (S)- Desmethyldesferrithiocin: Iron-Clearing Properties. Ann. N. Y. Acad. Sci. 1998, 850, 202-216.