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Title: 3-hydroxy-2(1H)-pyridinone chelating agents

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of said chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to said 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities.
Inventors:
 [1];  [1]
  1. (Berkeley, CA)
Issue Date:
OSTI Identifier:
870922
Assignee:
Regents of University of California (Oakland, CA) LBNL
Patent Number(s):
US 5624901
Contract Number:
AC03-76SF00098
Research Org:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA
Country of Publication:
United States
Language:
English
Subject:
3-hydroxy-2; 1h; -pyridinone; chelating; agents; disclosed; series; improved; metal; highly; effective; injection; oral; administration; toxicity; incorporate; structure; 1-hydroxy-2-pyridinone; 2-hopo; 3-hydroxy-2-pyridinone; moieties; substituted; carbamoyl; ortho; hydroxy; oxo; hydroxypyridinone; electron-withdrawing; increases; acidity; hydroxypyridinones; complexes; amide; protons; form; strong; hydrogen; bonds; adjacent; hopo; oxygen; donor; stable; physiological; conditions; terminal; n-substituents; provides; degree; lipophilicity; increasing; activity; method; producing; compound; 3-hydroxy-1-alkyl-2; pyridinone; precursor; agent; safely; quantities; metal chelating; metal complexes; chelating agents; chelating agent; highly effective; metal complex; physiological conditions; agents disclosed; -pyridinone chelating; oral administration; hydrogen bonds; /514/530/999/