This program is focused on the identification of novel, orally effective iron chelators for the treatment of iron overload diseases. The study is divided into two segments: the synthesis of desferrioxamine prodrugs and the biological evaluation of these compounds in rat and Cebus monkey models. Preliminary studies in our laboratories have already shown that the concept of desferrioxamine prodrugs is a workable one. We have recently developed a scheme for the high yield synthesis of desferrioxamine and derivatives which will facilitate access to the projected prodrugs required in the study. We will employ a non iron overloaded, bile duct cannulated rat model for the preliminary evaluation of new compounds. Chelators which appear promising in these studies will be further evaluated in an iron overloaded Cebus monkey model. Both animal models are currently in active use in our laboratories.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL042817-02
Application #
3361128
Study Section
Special Emphasis Panel (SRC (BE))
Project Start
1989-05-01
Project End
1993-02-28
Budget Start
1990-03-01
Budget End
1991-02-28
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Pharmacy
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Bergeron, R J; Liu, C Z; McManis, J S et al. (1994) The desferrithiocin pharmacophore. J Med Chem 37:1411-7
Bergeron, R J; Liu, Z R; McManis, J S et al. (1992) Structural alterations in desferrioxamine compatible with iron clearance in animals. J Med Chem 35:4739-44
Bergeron, R J; Wiegand, J; McManis, J S et al. (1991) Synthesis and biological evaluation of hydroxamate-based iron chelators. J Med Chem 34:3182-7