Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-08-02
1997-04-29
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 18, 514348, 514350, 546256, 546261, 5462681, 546296, 530329, 530330, 530331, A61K 3806, A61K 3808, A61K 3144, C07D40112
Patent
active
056249012
ABSTRACT:
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.
REFERENCES:
patent: 4698431 (1987-10-01), Raymond et al.
White et al., Journal of Medicinal Chemistry, vol. 31 (No. 1), pp. 11-18, Jan. 1988.
Scott et al., Journal of the American Chemical Society, vol. 107 (No. 13) PP. 6540-6546 Nov. 1985.
Xu et al., "Specific Sequestering Agents for the Actinides. 28. Synthesis and Initial Evaluation of Multidentate 4-Carbamoyl-3-hydroxy-1-methyl-2-(1H)-pyridinone Ligands for in Vivo Plutonium (IV) Chelation.sup.1, " J. Med. Chem. 1995, 38, pp. 2606-2614.
P. Durbin et al, "In vivo Chelation of Am(III), Pu(IV), Np(V) and U(VI) in Mice by TREN-(Me-3,2-HOPO)", Chemical Abstracts, vol. 122, No. 1, 2 Jan. 1995, p. 517.
Uhlir et al., "Specific Agents for the Actinides. 21. Synthesis and Initial Biological Testing of Octadentate Mixed Catecholate-Hydroxypridinoate Ligands", J. Med. Chem. 1993, 36, pp. 504-509.
R.J. Bergeron et al., "Catecholamide Chelators for Actinide Enviromental and Human Decontamination", Chemical Abstracts, vol. 105, No. 25, 22 Dec. 1986, Columbus, Ohio, US, Abstract No. 221872Z, p. 374.
P.W. Durbin et al., "Specific Sequestering agents for the Actinides: Enhancement of Puutonium-238 Elimination from the Emice by Poly(catechoylamide) Ligands", Chemical Abstracts, vol. 101, No. 15, 8 Oct. 1984, Columbus Ohio, US; Abstract No. 125980e, p. 328.
R.A. Bulman et al., "An Examination of Some Complexing Agents for Ability to Remove Intracellularly Deposited Plutonium", Chemical Abstracts, vo. 92 No. 13, 31 Mar. 1980, Columbus, OH, US: Abstracts No. 106582f, p. 286.
M. Streater et al., "Novel 3-hydroxy-2(1H)-pyridinones. Synthesis, Iron(III)-Chelating Properties, and Biological Activity", Journal of Medicinal Chemistry, 1990, vol. 33, pp. 1749-1755.
Raymond Kenneth N.
Xu Jide
Rotman Alan L.
The Regents of the University of California
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