Design of Orally Active Iron Chelators

Acta Haematologica

Volumn 95, Issue 1, 1996, Pages 6-12

  Hider, Robert C ^a   Choudhury, Roxana ^a   Rai, Bijaya L ^a   Dehkordi, Lotfollah S ^a   Singh, Surinder ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Hydroxypyridinones; Iron chelation; Oral activity

Indexed keywords

3 HYDROXY 4 PYRIDONE DERIVATIVE; CHELATING AGENT; DEFEROXAMINE; DEFERRIFERRITHIOCIN; FERRIC ION; PRODRUG;

ARTICLE; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG DISTRIBUTION; DRUG SELECTIVITY; HUMAN; IRON CHELATION; LIVER METABOLISM; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; DRUG DESIGN; FERRIC COMPOUNDS; FERROUS COMPOUNDS; HUMANS; IRON CHELATING AGENTS; PRODRUGS; PYRIDONES; TISSUE DISTRIBUTION;

EID: 0030050709     PISSN: 00015792     EISSN: 14219662     Source Type: Journal    
DOI: 10.1159/000203851     Document Type: Article

References (23)

1. Porter JB, Huehns ER, Hider RC: The development of iron chelating drugs. Baillicres Clin Haematol 1989; 2:257-292.
2. Rowlands M, Tozer TN: Clinical Pharmacokinetics, Concepts and Applications. Baltimore. Williams &Wilkins. 1995.
3. Lea A, Hansch C, Elkins D: Partition coefficients and their uses. Chcm Rev 1971;71:525-555.
4. Travis S, Menzies I: Intestinal permeability: Functional assessment and significance. Clin Sci 1992; 82:471-480.
5. 5lCr-labelled EDTA, /.-rhamnose and polycthyleneglycol 400 as probe markers for assessment in vivo of human intestinal permeability. Clin Sci 1986; 71:71-80.
6. Hershko C, Grady RW, Link G: Phenolic cthyldiamine derivatives: A study of orally effective iron chelators. J Lab Clin Med 1984; 103:337-346.
7. Kontoghiorghes GJ, Goddard JG, Bartlett AN, Sheppard L: Pharmacokinetic studies in humans with the oral iron chelator 1,2-dimethyl-3-hydroxypyridin-4-one. Clin Pharmacol Thcr 1990; 48:255-260.
8. Porter JB, Singh S, Hoyes K.P, Epemolu O, Abeysinghe RD, Hider RC: Lessons from pre-clinical and clinical studies with l,2-diethyl-3-hydroxypyridin-4-one, CP94 and related compounds. Adv Exp Med Biol 1994; 356:361— 370.
9. Bergeron RJ. Streiff RR, Creary EA, Daniels RD, King W, Luchctta G, Wiegand J, Moerker T, Peter HH: A comparative study of the iron clearing properties of desferrithiocin analogues with desferrioxamine B in a Cebus monkey model. Blood 1993; 81:2166-2173.
10. Harris DC, Aisen P: Facilitation of Fc(II) au-toxidation by Fe(III) complexing agents. Bio-chim Biophys Acta 1973; 329:156-158.
11. Hider RC, Hall AD: Clinically useful chelators of tripositive elements. Prog Med Chem 1991; 28:41-187.
12. Xiao G, van der Helm D, Hider RC, Dobbin PS: Structure stability relationships of 3-hy-droxypyridin-4-one complexes. J Chcm Soc 1992:3265-3272.
13. Porter JB. Gyparaki M, Burke LC, Huehns ER, Sarpong P, Saez V, Hider RC: Iron mobilization from hepatocyte monolayer cultures by chelators: The importance of membrane permeability and the iron binding constant. Blood 1988; 72:1497-1508.
14. Streater M, Taylor PD, Hider RC, Porter JB: Novel 3-hydroxy-2(IH)pyridinone: Synthesis, iron(III) chelating properties and biological activity. J Med Chcm 1990:33:1749-1857.
15. Oldendorf WH: Lipid solubility and drug penetration of the blood brain barrier. Proc Soc Exp Biol Med 1974; 147:813-817.
16. Hershko C, Grady RW, Ccrami A: Mechanism of iron chelation in the hypertransfused rat: Definition of two alternate pathways of iron mobilisation. J Lab Clin Med 1978:92:144— 151.
17. Peter H: Industrial aspects of iron chelators: Pharmaceutical applications: in Spik G, Mon-trcvil J. Crichton RR, Mazurier J (eds): Proteins of Iron Storage and Transport. Amsterdam. Elsevier, 1985, pp 293-303.
18. Bergeron RJ, Wiegand J. Dioniu JB. Egli-Kor-makka M, Frei J, Hoxley-Tencer A, Peter HH: Evaluation of desferrithiocin and its synthetic analogues as orally effective iron chelators. J Med Chem 1991; 34:2072-2078.
19. Singh S, Epemolu RO, Dobbin PS, Tilbrook GS, Ellis BE, Damani LA, Hider RC: Urinary metabolic profiles in man and rat of 1,2-dimc-thyl-and 1,2-diethyl-substituted 3-hydroxypy-ridin-4-ones. Drug Metab Dispos 1992; 20: 256-264.
20. Singh S, Epemolu RO, Ackerman R. Porter JB, Hider RC: Development of 3-hydroxypyridin-4-ones which do not undergo extensive phase II metabolism. 3rd NIH-sponsored symposium on ‘The Development of Iron Chelators for Clinical Use’, 1993, pp 353-371.
21. Singh S: Therapeutically useful iron chelators. Chem Ind 1994;12:452-455.
22. Holme E, Jodal U, Linstedt S, Nordin I: Effects of pivalic acid-containing prodrugs on carnitine homeostasis and on response to fasting in chilcren. Scand J Clin Lab Invest 1992;52: 361-372.
23. Holme E, Gretcr J, Jacobsen CE, Linstedt S, Nordin I, Kristiansson B, Jodal U: Carnitine deficiency induced by pivampicilin and pivmc-cillinam therapy. Lancet 1989;ii:469—473.